BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic v...BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic variceal ligation,and most of them have lower platelet counts,which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders.Unfortunately,there is no defined treatment modality for CLD-induced thrombocytopenia.Recombinant human thrombopoietin(rhTPO)is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy;however,there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.AIM To evaluate the efficacy of rhTPO in the treatment of patients with CLDassociated thrombocytopenia undergoing invasive procedures.METHODS All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021.Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia.Adverse events related to treatment,such as bleeding,thrombosis,and disseminated intravascular coagulation,were also investigated.RESULTS Among the enrolled patients,78(78%)showed a platelet count increase after rhTPO use,while 22(22%)showed no significant change in platelet count.The mean platelet count after rhTPO treatment in all patients was 101.53±81.81×10^(9)/L,which was significantly improved compared to that at baseline(42.88±16.72×10^(9)/L),and this difference was statistically significant(P<0.001).In addition,patients were further divided into three subgroups according to their baseline platelet counts(<30×10^(9)/L,30-50×10^(9)/L,>50×10^(9)/L).Subgroup analyses showed that the median platelet counts after treatment were significantly higher(P<0.001,all).Ninety(90%)patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO.No serious adverse events related to rhTPO treatment were observed.Overall,rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.CONCLUSION rhTPO can improve platelet count,reduce the risk of bleeding,and decrease the platelet transfusion rate,which may promote the safety of invasive procedures and improve overall survival of patients with CLD.展开更多
Background:Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs).It causes thrombocytopenia and delays leukaphe...Background:Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs).It causes thrombocytopenia and delays leukapheresis.This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods:In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm).The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results:Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs.1 unit,P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 ×10^(9)/L (range 18-219) among patients who received rhTPO and 73 ×10^(9)/L (range 42-197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count <75 ×10^(9)/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%,P=0.297).Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 ×10^(9)/L vs. 11.0 days [95% confidence interval 8.6-13.4],P=0.011).The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups (P=0.362 andP=0.067,respectively).Conclusions:Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells,but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration:This trial has been registered in Clinicaltrials.gov as NCT03014102.展开更多
BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative t...BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.展开更多
AIM:To characterize changes of corneal nerve morphology and tear indices in patients with neurotrophic keratitis(NK)treated with recombinant human nerve growth factor(rhNGF).METHODS:In a prospective observational stud...AIM:To characterize changes of corneal nerve morphology and tear indices in patients with neurotrophic keratitis(NK)treated with recombinant human nerve growth factor(rhNGF).METHODS:In a prospective observational study,six patients(nine eyes)were locally treated with rhNGF.Visual acuity,corneal fluorescein staining score,the heights of the tear river,lipid layer thickness(LLT),tear ferning(TF)test,conjunctival impression cytology(CIC)examination,the densities of cornea subbasal nerve fibers were determined before and after treatment.RESULTS:Compared with baseline,there was a significant difference in corneal fluorescence staining scores(P<0.01);all patient corneal epithelial defects recovered completely within 8wk,but there was no significant improvement in the height of the tear river(P=0.202).LLT was significantly increased when compared with baseline(P=0.042);however,the function of conjunctival goblet cells and mucin content did not significantly improve using the TF test and CIC examination(P=0.557,P=0.539).After 8wk of treatment,the average corneal subbasal nerve fiber density increased significantly(P<0.01),as did the number of corneal nerve fiber branches(P=0.001).CONCLUSION:RhNGF can increase the density of corneal subbasal nerve fibers,promote the healing of persistent corneal epithelial defects and corneal ulcers in patients with NK,also improving tear function partially.展开更多
Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was tre...Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.展开更多
Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer...Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.展开更多
Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,ra...Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,radiotherapy group,and combined therapy group Ⅰ,Ⅱ,and Ⅲ after inoculating with Ecal09 cell suspension（1×107 cells/mL）.On the day of grouping,control group and radiotherapy group were injected normal saline,while radiotherapy group and 3 combined therapy groups received radiotherapy;besides,combined therapy group Ⅰ,Ⅱ,and Ⅲ was injected RH-endostatin of 2.5,5,10 mg/kg respectively.After 3-week therapy,the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined.In vitro,Eca109 cells were divided into control group,radiotherapy group,and combined therapy group.Forty-eight hours after treatment cell cycle distribution and apoptosis rate were detected,and the activity of VEGF signal paths was semiquantitatively analyzed.Results:Since the 6th day of treatment,the relative tumor proliferation rate of combined therapy group Ⅱ was lower than radiotherapy group（P<0.05） and 40%since the 15 th day.Average microvessel density and EGFR expression in combined therapy group Ⅱ were lower than radiotherapy group（P<0.05）.In vitro,the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells,while the apoptosis rate and the expression of VEGF,AKT,p-AKT,ERK1/2 and p-ERKl/2 in combined group were higher than that in radiotherapy group（P<0.05）.Conclusions:RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer,which may be partly realized by inhibiting the activity of VEGF related signal paths.展开更多
AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). ...AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl 4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl 4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl 4 treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1β, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1β, IL-1Ra and IL-6 expression during CCl 4-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl 4-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION: rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.展开更多
Background: Patients with intermediate to advanced hepatocellular carcinoma(HCC) are most commonly treated with transarterial chemoembolization(TACE). Previous studies showed that TACE combined with recombinant human ...Background: Patients with intermediate to advanced hepatocellular carcinoma(HCC) are most commonly treated with transarterial chemoembolization(TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5(H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an e ective nomogram for predicting individual survival outcomes of these patients.Methods: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat?sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101(TACE with H101 group) and 238 patients who received TACE without H101(TACE group) were analyzed. Overall survival(OS) was evaluated using the Kaplan–Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index(c?index) and calibration plots.Results: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group(1?year OS rate, 53.8% vs. 61.3%; 2?year OS rate, 33.4% vs. 44.2%; 3?year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha?fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram?predicted survival and observed survival. The c?index of the nomogram for predict?ing OS was 0.716(95% confidence interval 0.686–0.746).Conclusions: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.展开更多
AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METH...AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.展开更多
In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>...In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>25) were randomly divided into 3 groups. All the 3 groups had been supplied with nitrogen and caloricity according to the need of patients for 16 days. The rhGH therapy started 48 h after surgery and lasted for 14 days in two rhGH-treated groups in which rhGH was 0.2 and 0.4 U/(kg·d) respectively, and the resting group served as control one. The levels of nitrogen balance, prealbumin and safety variables (blood sugar, Na+, TT3 and TT4) were observed and com- pared among the three groups. The levels of nitrogen balance on the postoperative day (POD) 3 and 5 in the rhGH-treated groups were -1.28±3.19, 5.45±2.00 and -0.18±2.55, 6.11±1.60, respectively, which were significantly higher than those in the control group (-5.17±1.68 and -1.08±3.31, P<0.01). The values of prealbumin on the POD 3 and 5 in the rhGH-treated groups were 180.19±27.15, 194.44±50.82 and 194.94±29.65, 194.11±16.17, respectively, which were significantly higher than those in the control group (117.42±19.10 and 135.63±28.31, P<0.01). There was no sig- nificant difference between the rhGH 0.2 U/(kg·d) group and rhGH 0.4 U/(kg·d) group in both of the levels of nitrogen balance and prealbumin. It is concluded that the nutritional support therapy with adjuvant rhGH which starts 48 h after surgery improves the nutrition state of the patients with severe multiple trauma. It is safe for severe multiple trauma patients who accept rhGH at the dose of 0.2 and 0.4 U/(kg·d).展开更多
Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedicsurgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially ...Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedicsurgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially approved by the United States Food and Drug Administration only for single level anterior lumbar interbody fusion, nevertheless it is widely used by many surgeons with off-label indications. Despite advantages in bone formation, its use still remains a controversial issue and several complications have been described by authors who oppose their wide use.展开更多
Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to in...Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice. METHODS:A group of 42 Wistar rats were divided into 3 groups:sham operation (SO), bile duct ligation (BDL), and BDL and rhGH treatment (rhGH). By the end of the experiment,on day 7, the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope. RESULTS:Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml, significantly lower than that in the BDL group (0.65±0.04 EU/ml, P【0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P】0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%,significantly higher than that in the SO group and the rhGH group (P【0.05). There was no significant difference in bacteria translocation rate between the SO group and the rhGH group (P】0.05). Under an electron microscope , ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group. CONCLUSION:rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.展开更多
AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone ...AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients(80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent jointswere also carried out. Factors related to the patient(age, gender), the nonunion(location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure(graft and fixation type, amount of rhB MP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ~2 test was performed.RESULTS Eighty point nine percent of the nonunions treated with rh BMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients(17.8%) and it was apparent in the routine radiologi-cal evaluation of the nonunion site, in a mean time of 5.5 mo after the rh BMP-7 application(range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhB MP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification(P = 0.007). CONCLUSION Heterotopic ossification after the use of rh BMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.展开更多
Objective The aim of this study was to compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)and recombinant human granulocyte colonystimulating factor(rhG-CS...Objective The aim of this study was to compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)and recombinant human granulocyte colonystimulating factor(rhG-CSF)for the prevention of neutropenia in elderly breast cancer patients during adjuvant chemotherapy.Methods A total of 45 oncology inpatients with breast cancer,who received adjuvant chemotherapy and were older than 65 years from May 2017 to October 2018 in the General Hospital of the Northern Theater of the Chinese people’s Liberation Army,were included.Epirubivin Cyclophoshamide-Docetaxel(EC-T)sequential adjuvant chemotherapy was chosen.Forty-five patients were randomly divided into two groups;25 patients in the treatment group were treated with PEG-rhG-CSF and 20 patients in the control group were not treated with PEG-rhG-CSF,but only rhG-CSF.The experimental group was treated with the PEG-rhG-CSF at the end of chemotherapy for 24–48 h,with a 6 mg subcutaneous injection once per chemotherapy cycle.In the control group,rhG-CSF was administered after 48 h of chemotherapy,with a 100μg subcutaneous injection,1/d,d 1–7.The dosage could be increased step by step with the exacerbation of neutropenia.The primary aims of this study was to discover the incidence of leukopenia,neutropenia,neutrophilic fever,and adverse reactions in the two groups.Results The incidence of neutropenia,neutrophilic fever and adverse reactions decreased in the treatment group compared to the control group,but no significant difference existed between two groups(P>0.05).Patients in treatment group had a lower,but not statistically significant,incidence of adverse reactions(P>0.05).Conclusion Applying PEG-rhG-CSF could be effective in preventing neutropenia in elderly patients with postoperative adjuvant chemotherapy to treat breast cancer.It may effectively control the occurrence of neutropenia after chemotherapy and reduce the chance of infection.The incidence of side effects,such as fever and bone pain,was low.The adverse drug reactions were well tolerated by patients,which could ensure the smooth progress of chemotherapy.展开更多
To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1800 g were ...To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1800 g were randomly assigned to treatment group 1 (n=15, receiving subcutaneous rhEpo 150 U/kg·time), treatment group 2 (n=15, receiving 250 U/kg·time), three times a week for 6 weeks, and control group (n=15, no treatment was given).All preterm infants received supplements of vitamin E (20 IU) and iron (20 mg) each day. Our results showed that postnatal decline of hemoglobin (Hb) and hematocrit (Hct) were lessened in the treatment groups, particularly in the group 2 and the differences were very significant (P【0.0001 for all). Treated infants had significantly higher reticulocyte counts (Ret) (P【0.0001 for all), but there was no significant difference between the two treatment groups (P】0.05).Serum iron dropped significantly in the treatment groups as compared with control group (P【0.01 for all),展开更多
BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer...BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer.However,efficacy and safety of the current regimens for NSCLC is unsatisfactory.Therefore,there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIM To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin(Rh-endostain)using an infusion pump in retreated advanced NSCLC.METHODS Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited.These patients received continuous intravenous infusion of Rh-endostain using an infusion pump.Objective response rate(ORR),clinical benefit rate(CBR),median progression-free survival(mPFS),and incidences of adverse events(AEs)were analyzed after treatment.RESULTS A total of 45 patients with retreated advanced NSCLC were included,and all of them were evaluated.In these patients,ORR was 22.2%,CBR was 84.4%,and mPFS was 5.3 mo.The following AEs were observed,decreased hemoglobin(34 cases,75.6%),nausea/vomiting(32 cases,71.1%),elevated transaminase(24 cases,53.3%),leukopenia(16 cases,35.6%),thrombocytopenia(14 cases,31.1%),and constipation(1 case,3.4%).None of the patients had leukopenia,nausea/vomiting,and constipation of grade III and above.CONCLUSION The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump.Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.展开更多
The current study was designed to determine the safety,tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone[rhPTH(1-84)]used for the treatment of osteoporosis.In the single-dose format ...The current study was designed to determine the safety,tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone[rhPTH(1-84)]used for the treatment of osteoporosis.In the single-dose format pharmacokinetic study,thirty-six healthy male volunteers received three dose levels of rhPTH(1-84)subcutaneously:1,2,and 4μg/kg.The blood was timing drawn and the serum concentration of rhPTH(1-84)was determined by enzyme linked immunosorbent assay(ELISA).Serum concentration-time curves of PTH(1-84)exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration.Serum terminal half-time of PTH(1-84)was approximately 2 h.The parameters indicated the serum levels were directly proportional to the administered dose,with the mean Cmax and AUC0-24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg·h·mL-1over the dose range.The drug was well tolerated,the clinical symptoms were generally mild and of short duration.展开更多
Aim:To produce biologically active recombinant human (rh) ZP proteins in a human cell for use in sperm function tests.Methods:The human embryonic kidney cell line 293T was employed to produce rhZP1,rhZP2 and rhZP3 pro...Aim:To produce biologically active recombinant human (rh) ZP proteins in a human cell for use in sperm function tests.Methods:The human embryonic kidney cell line 293T was employed to produce rhZP1,rhZP2 and rhZP3 proteins individually and together by co-expression.Presence of these proteins in the culture medium and cell lysate was assessed by Western blotting analysis.The effect of the recombinant proteins on the human AR was assessed.Results:RhZP2 and rhZP3 were secreted into the culture medium,whereas rhZP1 was found only in the cell lysate.Interestingly,when all zona pellucida proteins were co-expressed in the same cells,rhZP1 was also secreted into the culture medium.However,despite the presence of all three ZP proteins in sufficient concentration and evidence of heavy glycosylation on gel electrophoresis,biological activity to induce the AR was not observed.Conclusion:RhZP1,rhZP2 and rhZP3 were successfully expressed in the human embryonic kidney cell line 293T.It appears that an interaction amongst these proteins may be required for release of rhZP1 from the cell.Although this approach is not satisfactory for producing active human ZP proteins,it makes a significant contribution to the under-standing of the structural and functional characteristics of the ZP proteins.(Asian J Androl 2004 Mar; 6:3-13)展开更多
基金Supported by the Science and Technology Development Plan of Suzhou,Jiangsu Province,China,No.SYS2020009.
文摘BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic variceal ligation,and most of them have lower platelet counts,which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders.Unfortunately,there is no defined treatment modality for CLD-induced thrombocytopenia.Recombinant human thrombopoietin(rhTPO)is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy;however,there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.AIM To evaluate the efficacy of rhTPO in the treatment of patients with CLDassociated thrombocytopenia undergoing invasive procedures.METHODS All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021.Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia.Adverse events related to treatment,such as bleeding,thrombosis,and disseminated intravascular coagulation,were also investigated.RESULTS Among the enrolled patients,78(78%)showed a platelet count increase after rhTPO use,while 22(22%)showed no significant change in platelet count.The mean platelet count after rhTPO treatment in all patients was 101.53±81.81×10^(9)/L,which was significantly improved compared to that at baseline(42.88±16.72×10^(9)/L),and this difference was statistically significant(P<0.001).In addition,patients were further divided into three subgroups according to their baseline platelet counts(<30×10^(9)/L,30-50×10^(9)/L,>50×10^(9)/L).Subgroup analyses showed that the median platelet counts after treatment were significantly higher(P<0.001,all).Ninety(90%)patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO.No serious adverse events related to rhTPO treatment were observed.Overall,rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.CONCLUSION rhTPO can improve platelet count,reduce the risk of bleeding,and decrease the platelet transfusion rate,which may promote the safety of invasive procedures and improve overall survival of patients with CLD.
基金This work was supported by Beijing Hope Run Special Fund of Cancer Foundation of China(LC2016B03)。
文摘Background:Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs).It causes thrombocytopenia and delays leukapheresis.This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods:In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm).The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results:Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs.1 unit,P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 ×10^(9)/L (range 18-219) among patients who received rhTPO and 73 ×10^(9)/L (range 42-197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count <75 ×10^(9)/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%,P=0.297).Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 ×10^(9)/L vs. 11.0 days [95% confidence interval 8.6-13.4],P=0.011).The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups (P=0.362 andP=0.067,respectively).Conclusions:Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells,but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration:This trial has been registered in Clinicaltrials.gov as NCT03014102.
文摘BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.
基金Supported by the Shaanxi Provincial Department of Science and Technology(No.2021SF-331)。
文摘AIM:To characterize changes of corneal nerve morphology and tear indices in patients with neurotrophic keratitis(NK)treated with recombinant human nerve growth factor(rhNGF).METHODS:In a prospective observational study,six patients(nine eyes)were locally treated with rhNGF.Visual acuity,corneal fluorescein staining score,the heights of the tear river,lipid layer thickness(LLT),tear ferning(TF)test,conjunctival impression cytology(CIC)examination,the densities of cornea subbasal nerve fibers were determined before and after treatment.RESULTS:Compared with baseline,there was a significant difference in corneal fluorescence staining scores(P<0.01);all patient corneal epithelial defects recovered completely within 8wk,but there was no significant improvement in the height of the tear river(P=0.202).LLT was significantly increased when compared with baseline(P=0.042);however,the function of conjunctival goblet cells and mucin content did not significantly improve using the TF test and CIC examination(P=0.557,P=0.539).After 8wk of treatment,the average corneal subbasal nerve fiber density increased significantly(P<0.01),as did the number of corneal nerve fiber branches(P=0.001).CONCLUSION:RhNGF can increase the density of corneal subbasal nerve fibers,promote the healing of persistent corneal epithelial defects and corneal ulcers in patients with NK,also improving tear function partially.
基金supported by Clinical Special Funds of China University Medical Journals(No:11321375)
文摘Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.
基金supported by Liaoning BaiQianWan Talents Program(No.2012921017)
文摘Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.
基金supported by the Science and Technology Development Plan of Henan province(No.122102310245)
文摘Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,radiotherapy group,and combined therapy group Ⅰ,Ⅱ,and Ⅲ after inoculating with Ecal09 cell suspension（1×107 cells/mL）.On the day of grouping,control group and radiotherapy group were injected normal saline,while radiotherapy group and 3 combined therapy groups received radiotherapy;besides,combined therapy group Ⅰ,Ⅱ,and Ⅲ was injected RH-endostatin of 2.5,5,10 mg/kg respectively.After 3-week therapy,the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined.In vitro,Eca109 cells were divided into control group,radiotherapy group,and combined therapy group.Forty-eight hours after treatment cell cycle distribution and apoptosis rate were detected,and the activity of VEGF signal paths was semiquantitatively analyzed.Results:Since the 6th day of treatment,the relative tumor proliferation rate of combined therapy group Ⅱ was lower than radiotherapy group（P<0.05） and 40%since the 15 th day.Average microvessel density and EGFR expression in combined therapy group Ⅱ were lower than radiotherapy group（P<0.05）.In vitro,the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells,while the apoptosis rate and the expression of VEGF,AKT,p-AKT,ERK1/2 and p-ERKl/2 in combined group were higher than that in radiotherapy group（P<0.05）.Conclusions:RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer,which may be partly realized by inhibiting the activity of VEGF related signal paths.
基金Supported by The Chinese Human Liver Proteome Project, No. 2004BA711A19-08National 863 Project, No.2007AA02Z100
文摘AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl 4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl 4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl 4 treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1β, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1β, IL-1Ra and IL-6 expression during CCl 4-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl 4-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION: rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.
文摘Background: Patients with intermediate to advanced hepatocellular carcinoma(HCC) are most commonly treated with transarterial chemoembolization(TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5(H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an e ective nomogram for predicting individual survival outcomes of these patients.Methods: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat?sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101(TACE with H101 group) and 238 patients who received TACE without H101(TACE group) were analyzed. Overall survival(OS) was evaluated using the Kaplan–Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index(c?index) and calibration plots.Results: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group(1?year OS rate, 53.8% vs. 61.3%; 2?year OS rate, 33.4% vs. 44.2%; 3?year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha?fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram?predicted survival and observed survival. The c?index of the nomogram for predict?ing OS was 0.716(95% confidence interval 0.686–0.746).Conclusions: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.
文摘AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.
文摘In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>25) were randomly divided into 3 groups. All the 3 groups had been supplied with nitrogen and caloricity according to the need of patients for 16 days. The rhGH therapy started 48 h after surgery and lasted for 14 days in two rhGH-treated groups in which rhGH was 0.2 and 0.4 U/(kg·d) respectively, and the resting group served as control one. The levels of nitrogen balance, prealbumin and safety variables (blood sugar, Na+, TT3 and TT4) were observed and com- pared among the three groups. The levels of nitrogen balance on the postoperative day (POD) 3 and 5 in the rhGH-treated groups were -1.28±3.19, 5.45±2.00 and -0.18±2.55, 6.11±1.60, respectively, which were significantly higher than those in the control group (-5.17±1.68 and -1.08±3.31, P<0.01). The values of prealbumin on the POD 3 and 5 in the rhGH-treated groups were 180.19±27.15, 194.44±50.82 and 194.94±29.65, 194.11±16.17, respectively, which were significantly higher than those in the control group (117.42±19.10 and 135.63±28.31, P<0.01). There was no sig- nificant difference between the rhGH 0.2 U/(kg·d) group and rhGH 0.4 U/(kg·d) group in both of the levels of nitrogen balance and prealbumin. It is concluded that the nutritional support therapy with adjuvant rhGH which starts 48 h after surgery improves the nutrition state of the patients with severe multiple trauma. It is safe for severe multiple trauma patients who accept rhGH at the dose of 0.2 and 0.4 U/(kg·d).
文摘Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedicsurgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially approved by the United States Food and Drug Administration only for single level anterior lumbar interbody fusion, nevertheless it is widely used by many surgeons with off-label indications. Despite advantages in bone formation, its use still remains a controversial issue and several complications have been described by authors who oppose their wide use.
文摘Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice. METHODS:A group of 42 Wistar rats were divided into 3 groups:sham operation (SO), bile duct ligation (BDL), and BDL and rhGH treatment (rhGH). By the end of the experiment,on day 7, the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope. RESULTS:Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml, significantly lower than that in the BDL group (0.65±0.04 EU/ml, P【0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P】0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%,significantly higher than that in the SO group and the rhGH group (P【0.05). There was no significant difference in bacteria translocation rate between the SO group and the rhGH group (P】0.05). Under an electron microscope , ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group. CONCLUSION:rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.
基金The European Union(European Social Fund-ESF)Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework(NSRF)-Research Funding Program:Heracleitus Ⅱ
文摘AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients(80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent jointswere also carried out. Factors related to the patient(age, gender), the nonunion(location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure(graft and fixation type, amount of rhB MP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ~2 test was performed.RESULTS Eighty point nine percent of the nonunions treated with rh BMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients(17.8%) and it was apparent in the routine radiologi-cal evaluation of the nonunion site, in a mean time of 5.5 mo after the rh BMP-7 application(range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhB MP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification(P = 0.007). CONCLUSION Heterotopic ossification after the use of rh BMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.
文摘Objective The aim of this study was to compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)and recombinant human granulocyte colonystimulating factor(rhG-CSF)for the prevention of neutropenia in elderly breast cancer patients during adjuvant chemotherapy.Methods A total of 45 oncology inpatients with breast cancer,who received adjuvant chemotherapy and were older than 65 years from May 2017 to October 2018 in the General Hospital of the Northern Theater of the Chinese people’s Liberation Army,were included.Epirubivin Cyclophoshamide-Docetaxel(EC-T)sequential adjuvant chemotherapy was chosen.Forty-five patients were randomly divided into two groups;25 patients in the treatment group were treated with PEG-rhG-CSF and 20 patients in the control group were not treated with PEG-rhG-CSF,but only rhG-CSF.The experimental group was treated with the PEG-rhG-CSF at the end of chemotherapy for 24–48 h,with a 6 mg subcutaneous injection once per chemotherapy cycle.In the control group,rhG-CSF was administered after 48 h of chemotherapy,with a 100μg subcutaneous injection,1/d,d 1–7.The dosage could be increased step by step with the exacerbation of neutropenia.The primary aims of this study was to discover the incidence of leukopenia,neutropenia,neutrophilic fever,and adverse reactions in the two groups.Results The incidence of neutropenia,neutrophilic fever and adverse reactions decreased in the treatment group compared to the control group,but no significant difference existed between two groups(P>0.05).Patients in treatment group had a lower,but not statistically significant,incidence of adverse reactions(P>0.05).Conclusion Applying PEG-rhG-CSF could be effective in preventing neutropenia in elderly patients with postoperative adjuvant chemotherapy to treat breast cancer.It may effectively control the occurrence of neutropenia after chemotherapy and reduce the chance of infection.The incidence of side effects,such as fever and bone pain,was low.The adverse drug reactions were well tolerated by patients,which could ensure the smooth progress of chemotherapy.
文摘To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1800 g were randomly assigned to treatment group 1 (n=15, receiving subcutaneous rhEpo 150 U/kg·time), treatment group 2 (n=15, receiving 250 U/kg·time), three times a week for 6 weeks, and control group (n=15, no treatment was given).All preterm infants received supplements of vitamin E (20 IU) and iron (20 mg) each day. Our results showed that postnatal decline of hemoglobin (Hb) and hematocrit (Hct) were lessened in the treatment groups, particularly in the group 2 and the differences were very significant (P【0.0001 for all). Treated infants had significantly higher reticulocyte counts (Ret) (P【0.0001 for all), but there was no significant difference between the two treatment groups (P】0.05).Serum iron dropped significantly in the treatment groups as compared with control group (P【0.01 for all),
文摘BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer.However,efficacy and safety of the current regimens for NSCLC is unsatisfactory.Therefore,there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIM To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin(Rh-endostain)using an infusion pump in retreated advanced NSCLC.METHODS Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited.These patients received continuous intravenous infusion of Rh-endostain using an infusion pump.Objective response rate(ORR),clinical benefit rate(CBR),median progression-free survival(mPFS),and incidences of adverse events(AEs)were analyzed after treatment.RESULTS A total of 45 patients with retreated advanced NSCLC were included,and all of them were evaluated.In these patients,ORR was 22.2%,CBR was 84.4%,and mPFS was 5.3 mo.The following AEs were observed,decreased hemoglobin(34 cases,75.6%),nausea/vomiting(32 cases,71.1%),elevated transaminase(24 cases,53.3%),leukopenia(16 cases,35.6%),thrombocytopenia(14 cases,31.1%),and constipation(1 case,3.4%).None of the patients had leukopenia,nausea/vomiting,and constipation of grade III and above.CONCLUSION The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump.Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.
文摘The current study was designed to determine the safety,tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone[rhPTH(1-84)]used for the treatment of osteoporosis.In the single-dose format pharmacokinetic study,thirty-six healthy male volunteers received three dose levels of rhPTH(1-84)subcutaneously:1,2,and 4μg/kg.The blood was timing drawn and the serum concentration of rhPTH(1-84)was determined by enzyme linked immunosorbent assay(ELISA).Serum concentration-time curves of PTH(1-84)exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration.Serum terminal half-time of PTH(1-84)was approximately 2 h.The parameters indicated the serum levels were directly proportional to the administered dose,with the mean Cmax and AUC0-24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg·h·mL-1over the dose range.The drug was well tolerated,the clinical symptoms were generally mild and of short duration.
文摘Aim:To produce biologically active recombinant human (rh) ZP proteins in a human cell for use in sperm function tests.Methods:The human embryonic kidney cell line 293T was employed to produce rhZP1,rhZP2 and rhZP3 proteins individually and together by co-expression.Presence of these proteins in the culture medium and cell lysate was assessed by Western blotting analysis.The effect of the recombinant proteins on the human AR was assessed.Results:RhZP2 and rhZP3 were secreted into the culture medium,whereas rhZP1 was found only in the cell lysate.Interestingly,when all zona pellucida proteins were co-expressed in the same cells,rhZP1 was also secreted into the culture medium.However,despite the presence of all three ZP proteins in sufficient concentration and evidence of heavy glycosylation on gel electrophoresis,biological activity to induce the AR was not observed.Conclusion:RhZP1,rhZP2 and rhZP3 were successfully expressed in the human embryonic kidney cell line 293T.It appears that an interaction amongst these proteins may be required for release of rhZP1 from the cell.Although this approach is not satisfactory for producing active human ZP proteins,it makes a significant contribution to the under-standing of the structural and functional characteristics of the ZP proteins.(Asian J Androl 2004 Mar; 6:3-13)
