Developing cost-effective,robust and stable non-precious metal catalysts for oxygen reduction reaction(ORR) is of paramount importance for electrochemical energy conversion devices such as fuel cells and metal-air bat...Developing cost-effective,robust and stable non-precious metal catalysts for oxygen reduction reaction(ORR) is of paramount importance for electrochemical energy conversion devices such as fuel cells and metal-air batteries.Although Fe-N-C single atom catalysts(SACs) have been hailed as the most promising candidate due to the optimal binding strength of ORR intermediates on the Fe-N_(4) sites,they suffer from serious mass transport limitations as microporous templates/substrates,i.e.,zeolitic imidazolate frameworks(ZIFs),are usually employed to host the active sites.Motivated by this challenge,we herein develop a hydrogen-bonded organic framework(HOF)-assisted pyrolysis strategy to construct hierarchical micro/mesoporous carbon nanoplates for the deposition of atomically dispersed Fe-N_(4) sites.Such a design is accomplished by employing HOF nanoplates assembled from 2-aminoterephthalic acid(NH_(2)-BDC) and p-phenylenediamine(PDA) as both soft templates and C,N precursors.Benefitting from the structural merits inherited from HOF templates,the optimized catalyst(denoted as Fe-N-C SAC-950) displays outstanding ORR activity with a high half-wave potential of 0.895 V(vs.reversible hydrogen electrode(RHE)) and a small overpotential of 356 mV at 10 mA cm^(-2) for the oxygen evolution reaction(OER).More excitingly,its application potential is further verified by delivering superb rechargeability and cycling stability with a nearly unfading charge-discharge gap of 0.72 V after 160 h.Molecular dynamics(MD) simulations reveal that micro/mesoporous structure is conducive to the rapid mass transfer of O_(2),thus enhancing the ORR performance.In situ Raman results further indicate that the conversion of O_(2) to~*O_(2)-the rate-determining step(RDS) for Fe-N-C SAC-950.This work will provide a versatile strategy to construct single atom catalysts with desirable catalytic properties.展开更多
Background:Drug-induced liver damage is a severe medical issue that affects people all over the world.Sorafenib has some side effects that cause liver injury.A dietary medicinal plant called Penthorum chinense Pursh.(...Background:Drug-induced liver damage is a severe medical issue that affects people all over the world.Sorafenib has some side effects that cause liver injury.A dietary medicinal plant called Penthorum chinense Pursh.(PCP)has hepatoprotective properties.There are currently few reports on PCP’s protective impact and mechanism against sorafenib-induced liver injury.Methods:To create a liver injury model,sorafenib was administered to BRL-3A cells.Cell viability assays,immunofluorescence tests,Western blotting,real-time quantitative PCR,and high-content imaging systems were utilized to examine PCP’s effect and mechanism.Results:In this study,PCP treatment mitigated the liver damage caused by sorafenib by enhancing cell survival,lowering lipid reactive oxygen species and malondialdehyde levels,and elevating glutathione levels.In addition,PCP can enhance the protein expression of cystine/glutamate transporter xCT and glutathione peroxidase 4,reduce iron content and alleviate mitochondrial toxicity.Further mechanism studies revealed that PCP inhibited ferroptosis by promoting the production of nuclear factor E2-related factor 2 nuclear translocation and subsequently affecting target genes(HO-1 and NQO1).Conclusion:Together,PCP regulates the nuclear factor E2-related factor 2 pathway,which helps to lessen ferroptosis brought on by sorafenib.展开更多
Small intestinal bacterial overgrowth has been found to be associated with a variety of gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, and, in recent years, diabetes mellitus ...Small intestinal bacterial overgrowth has been found to be associated with a variety of gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, and, in recent years, diabetes mellitus and systemic sclerosis, among other extraintestinal diseases. Several novel diagnostic tools for small intestinal bacterial overgrowth have emerged in recent years, and several therapeutic approaches have been proposed. Therefore, it has become necessary to find an effective, safe, and simple diagnostic method and a safe treatment modality. This article provides a review of current diagnostic and therapeutic approaches to small intestinal bacterial overgrowth.展开更多
Rifaximin in the Treatment of Gastroesophageal Reflux Disease (GERD) is a common clinical disorder, the most common symptom of which is a burning sensation behind the breastbone (heartburn) or reflux of stomach conten...Rifaximin in the Treatment of Gastroesophageal Reflux Disease (GERD) is a common clinical disorder, the most common symptom of which is a burning sensation behind the breastbone (heartburn) or reflux of stomach contents into the upper pharynx (acid reflux). The prevalence in China is increasing year by year, which can affect the quality of life of patients and also increase the economic burden on families and society. The pathogenesis of GERD is still unclear, and some studies suggest that intestinal microecology may be closely related to the development of GERD. Rifaximin is not readily absorbed orally and acts locally in the intestine, so it has mild adverse effects and good safety, and can be used to treat gastrointestinal diseases such as irritable bowel syndrome, traveler’s diarrhea, small intestinal bacterial overgrowth, diverticulosis, inflammatory bowel disease and hepatic encephalopathy. Therefore, this paper focuses on intestinal microecology as a possible pathogenesis of GERD and further explores the feasibility of rifaximin for the treatment of GERD.展开更多
To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham...To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.展开更多
Prenatal overweight/obesity(OW/OB)can alter colostrum lipid patterns,thereby affecting the lipid metabolism and even the cognitive and healthy development of infants.However,studies on changes in colostrum lipids in t...Prenatal overweight/obesity(OW/OB)can alter colostrum lipid patterns,thereby affecting the lipid metabolism and even the cognitive and healthy development of infants.However,studies on changes in colostrum lipids in the context of OW/OB are limited,particularly for glycerides and polar lipids.Therefore,this study investigated the infl uence of maternal prenatal weight on colostrum in lipid subclasses and molecular species.The concentration of triacylglycerols(TAGs)in the colostrum of the OW/OB group(35894.43 mg/L)was higher than that of the normal weight(NW)group(26639.20 mg/L),suggesting that colostrum from OW/OB mothers could provide more energy to their infants.Further analysis of the fatty acid composition of TAGs revealed that elevated maternal body weight enhanced the concentration of TAGs containing saturated or n-6 fatty acids and shortened the carbon number of TAGs.Docosahexaenoic acid(DHA)/arachidonic acid(AA)/choline-containing lipids,such as DHA-containing TAGs,AA/DHA-containing phosphatidylethanolamine,and choline-containing phospholipids,were present in higher levels in the colostrum of OW/OB mothers than NW mothers.However,the concentrations of palmitic acid-containing TAGs,linoleic acid-containing TAGs,dihomo-γ-linolenic acid-containing TAGs,and polar lipids and the ratio of TAGs containing n-6 fatty acid/n-3 fatty acid were signifi cantly higher in the colostrum of OW/OB mothers than in that of NW mothers.The fatty acid composition and sphingoid bases of sphingolipids were also altered due to elevated body weight.In conclusion,OW/OB affects colostrum lipids with respect to composition,concentration,and percentage.Although the colostrum of healthy OW/OB mothers can provide suffi cient DHA/AA/choline-containing lipids to their infants,normalization of body weight and fat reserves should be considered as a strategy for highquality human milk lipids.展开更多
Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuropro...Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.展开更多
Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury...Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT （cTns） in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events （MACEs）. Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit （URL） in 133 （13.2%） patients, among which 22 （2.2%） were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 （P = 0.33, 95% CI： 0.74-2.46）. In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.展开更多
The Upper Ordovician–Lower Silurian mudstones(including the Wufeng, Guanyinqiao and Longmaxi Formations) in the Sichuan Basin are some of the most important shale gas plays in China. In order to enhance our understan...The Upper Ordovician–Lower Silurian mudstones(including the Wufeng, Guanyinqiao and Longmaxi Formations) in the Sichuan Basin are some of the most important shale gas plays in China. In order to enhance our understanding of the process of formation of organic carbon up to 10%, optical, microscopy and geochemical methods have been used to investigate the petrographic and geochemical characteristics of the formation. Firstly, three mudstone lithofacies were identified based on a wide variety of mudstone laminations. These are:(a) indistinctly laminated mudstone;(b) parallellaminated mudstone; and(c) nonparallel-laminated mudstone. Then, combining with the evidence from depocenter migration, Th/U ratios and total organic carbon, the abundant organo-minerallic fabrics suggest that organic carbon was preferentially deposited and preserved in anoxic, low energy and stagnant water conditions during deposition of the Wufeng and Longmaxi Formations. On the contrary, the Guanyinqiao Formation with poor organic carbon was deposited in oxic and high-energy water conditions.展开更多
BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK...BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.展开更多
Objective: Solute carrier family 38(SLC38 s) transporters play important roles in amino acid transportation and signaling transduction. However, their genetic alterations and biological roles in tumors are still large...Objective: Solute carrier family 38(SLC38 s) transporters play important roles in amino acid transportation and signaling transduction. However, their genetic alterations and biological roles in tumors are still largely unclear.This study aimed to elucidate the genetic signatures of SLC38 s transporters and their implications in esophageal squamous cell carcinoma(ESCC).Methods: Analyses on somatic mutation and copy number alterations(CNAs) of SLC38 A3 were performed as described. Immunohistochemistry(IHC) assay and Western blot assay were used to detect the protein expression level. MTS assay, colony formation assay, transwell assay and wound healing assay were used to explore the malignant phenotypes of ESCC cells. Immunofluorescence assay was used to verify the colocalization of two indicated proteins and immunopreciptation assay was performed to confirm the interaction of proteins.Results: Our findings revealed that SLC38 s family was significantly disrupted in ESCC, with high frequent CNAs and few somatic mutations. SLC38 A3 was the most frequent loss gene among them and was linked to poor survival and lymph node metastasis. The expression of SLC38 A3 was lower in tumor tissues compared to that in normal tissues, which was also significantly associated with worse clinical outcome. Further experiments revealed that depletion of SLC38 A3 could promote EMT in ESCC cell lines, and the interaction of SLC38 A3 and SETDB1 might lead to the reduced transcription of Snail. Pharmacogenomic analyses demonstrated that fifteen inhibitors were showed significantly correlated with SLC38 A3 expression.Conclusions: Our investigations have provided insights that SLC38 A3 could act as a suppressor in EMT pathway and serve as a prognostic factor and predictor of differential drug sensitivities in ESCC.展开更多
BACKGROUND Warthin’s tumor(WT)is composed of several cysts that are lined with tall,bilayered oncocytic columnar cells and lymphoid stroma.Within WT,the two components rarely transform into carcinoma or lymphoma,and ...BACKGROUND Warthin’s tumor(WT)is composed of several cysts that are lined with tall,bilayered oncocytic columnar cells and lymphoid stroma.Within WT,the two components rarely transform into carcinoma or lymphoma,and when it does,carcinoma is the most common type.Approximately 28 cases of lymphoma with WT have been reported,most of which were non-Hodgkin lymphomas,and only a few cases were Hodgkin lymphomas.In the present report,we studied a case of diffuse large B cell lymphoma(DLBCL)arising from follicular lymphoma(FL)with WT in the parotid gland and its immunophenotypic and genetic features.CASE SUMMARY A 67-year-old man presented with a slowly enlarging right cheek mass for 12 years,and the mass began to change in size over a 2-mo time period.Over time,the patient felt mild local pain and right cheek discomfort.His medical history included a hepatitis B virus infection for 20 years and 30 years of smoking.Gross examination of the excised specimen showed a gray-red and gray-white appearance and a soft texture lobulated external surface neoplasm that measured 9 cm×8 cm×7 cm and was well circumscribed by relative normal parotid gland tissue.In cross section,the cut surfaces of the neoplasm were multicystic and had a homogeneous scaly appearance.A small fluid was discovered in the cyst.Bilateral oxyphilic,cuboidal or polygonal epithelium cells and lymphoid intraparenchymal components were observed.Many medium-to large-sized lymphoid cells were observed diffusely in part of the neoplasm,and a few secondary lymphoid follicles were observed at the center or edge of the neoplasm.Immunohistochemical staining showed that the columnar oncocytic cells were positive for AE1/AE3;neoplastic cells located in coarctate follicular were positive for CD20,Pax-5,bcl-2 and bcl-6;and the adjacent diffusely medium-to large-sized lymphoid cells were positive for Pax-5,bcl-6,CD20,MUM-1,bcl-2 and CD79a.The bcl-6(3q27)break-apart rearrangement was observed,and an Epstein Barr virus test was negative in the tumor cells.The patient survived 6 months after being diagnosed without any treatment.CONCLUSION WT-associated lymphoma is a very rare neoplasm in the parotid gland.Most cases are B cell non-Hodgkin lymphomas and involve middle-age and older males.This case highlights the extremely rare association of DLBCL arising from FL with WT and the importance of deliberate evaluation of the WT intraparenchymal stroma.Molecular detection techniques have potential advantages in the diagnosis of lymphoma with WT.展开更多
A novel electrochemical immunoassay for cardiac troponin Ⅰ （cTnI） combining the concepts of the dual monoclonal antibody ＂sandwich＂ principle, the silver enhancement on the nano-gold particle, and the SBA-15 meso...A novel electrochemical immunoassay for cardiac troponin Ⅰ （cTnI） combining the concepts of the dual monoclonal antibody ＂sandwich＂ principle, the silver enhancement on the nano-gold particle, and the SBA-15 mesoporous modified carbon paste electrode （SBA-MCPE） is described. Four main steps were carried out to obtain the analytical signal, i.e., electrode preparation, immunoreaction, silver enhancement, and anodic stripping voltammetric detection. A linear relationship between the anodic stripping peak current and concentration of cTnI from 0.5 to 5.0 ng/mL and a limit of detection of 0.2 ng/mL of cTnI were obtained.展开更多
Objective: To study the effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells. Methods: Regenerated tissue extracts after liver injury...Objective: To study the effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells. Methods: Regenerated tissue extracts after liver injury were used to induce SK-HEP1 cells after enrichment, their effects on the proliferation, differentiation, migration and invasion of SK-HEPI cells were observed through in vitro cell culture, MTT, flow cytometry and transwell assays. Results:In response to the action of regenerated tissue extracts after liver injury, SK-HEP1 cells were blocked in G_0/G_1 phase, their growth rate was distinctly reduced. The number of SK-HEP1^(-fj)colonies decreased. The migration ability of SK-HEPI cells showed a decreased trend on day7 and day 11 after induction. SK-HEPl's invasion ability clearly decreased on days 7 and11 after induction, especially on day 7. Conclusions: To a certain extent, regenerated tissue extracts after liver injury can inhibit the proliferation, differentiation, migration and invasion of hepatoma cells, showing an important potential of being a differentiating agent for the treatment of liver cancer.展开更多
基金financially supported by the National Key R&D Program of China(2022YFB4004100)the National Natural Science Foundation of China(22272161)+6 种基金the Jilin Province Science and Technology Development Program(20230101367JC)financially supported by the National Natural Science Foundation of China(22073094)the Science and Technology Development Program of Jilin Province(20210402059GH)the Science and Technology Plan Projects of Yunnan Province(202101BC070001–007)the Major Science and Technology Projects for Independent Innovation of China FAW Group Co.,Ltd(20220301018GX)the essential support of the Network and Computing Center,CIAC,CASthe Computing Center of Jilin Province。
文摘Developing cost-effective,robust and stable non-precious metal catalysts for oxygen reduction reaction(ORR) is of paramount importance for electrochemical energy conversion devices such as fuel cells and metal-air batteries.Although Fe-N-C single atom catalysts(SACs) have been hailed as the most promising candidate due to the optimal binding strength of ORR intermediates on the Fe-N_(4) sites,they suffer from serious mass transport limitations as microporous templates/substrates,i.e.,zeolitic imidazolate frameworks(ZIFs),are usually employed to host the active sites.Motivated by this challenge,we herein develop a hydrogen-bonded organic framework(HOF)-assisted pyrolysis strategy to construct hierarchical micro/mesoporous carbon nanoplates for the deposition of atomically dispersed Fe-N_(4) sites.Such a design is accomplished by employing HOF nanoplates assembled from 2-aminoterephthalic acid(NH_(2)-BDC) and p-phenylenediamine(PDA) as both soft templates and C,N precursors.Benefitting from the structural merits inherited from HOF templates,the optimized catalyst(denoted as Fe-N-C SAC-950) displays outstanding ORR activity with a high half-wave potential of 0.895 V(vs.reversible hydrogen electrode(RHE)) and a small overpotential of 356 mV at 10 mA cm^(-2) for the oxygen evolution reaction(OER).More excitingly,its application potential is further verified by delivering superb rechargeability and cycling stability with a nearly unfading charge-discharge gap of 0.72 V after 160 h.Molecular dynamics(MD) simulations reveal that micro/mesoporous structure is conducive to the rapid mass transfer of O_(2),thus enhancing the ORR performance.In situ Raman results further indicate that the conversion of O_(2) to~*O_(2)-the rate-determining step(RDS) for Fe-N-C SAC-950.This work will provide a versatile strategy to construct single atom catalysts with desirable catalytic properties.
基金supported by the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SCMR202103)to Jian LiTibet Autonomous Region Science and Technology Plan(high-tech social development)project(No.XZ202201ZY0031G)to Yi-Xi YangAnti-infective Agent Creation Engineering Research Centre of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of pharmacy,Chengdu University(No.AAC2023002)to Qiu-Xia Lu.
文摘Background:Drug-induced liver damage is a severe medical issue that affects people all over the world.Sorafenib has some side effects that cause liver injury.A dietary medicinal plant called Penthorum chinense Pursh.(PCP)has hepatoprotective properties.There are currently few reports on PCP’s protective impact and mechanism against sorafenib-induced liver injury.Methods:To create a liver injury model,sorafenib was administered to BRL-3A cells.Cell viability assays,immunofluorescence tests,Western blotting,real-time quantitative PCR,and high-content imaging systems were utilized to examine PCP’s effect and mechanism.Results:In this study,PCP treatment mitigated the liver damage caused by sorafenib by enhancing cell survival,lowering lipid reactive oxygen species and malondialdehyde levels,and elevating glutathione levels.In addition,PCP can enhance the protein expression of cystine/glutamate transporter xCT and glutathione peroxidase 4,reduce iron content and alleviate mitochondrial toxicity.Further mechanism studies revealed that PCP inhibited ferroptosis by promoting the production of nuclear factor E2-related factor 2 nuclear translocation and subsequently affecting target genes(HO-1 and NQO1).Conclusion:Together,PCP regulates the nuclear factor E2-related factor 2 pathway,which helps to lessen ferroptosis brought on by sorafenib.
文摘Small intestinal bacterial overgrowth has been found to be associated with a variety of gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, and, in recent years, diabetes mellitus and systemic sclerosis, among other extraintestinal diseases. Several novel diagnostic tools for small intestinal bacterial overgrowth have emerged in recent years, and several therapeutic approaches have been proposed. Therefore, it has become necessary to find an effective, safe, and simple diagnostic method and a safe treatment modality. This article provides a review of current diagnostic and therapeutic approaches to small intestinal bacterial overgrowth.
文摘Rifaximin in the Treatment of Gastroesophageal Reflux Disease (GERD) is a common clinical disorder, the most common symptom of which is a burning sensation behind the breastbone (heartburn) or reflux of stomach contents into the upper pharynx (acid reflux). The prevalence in China is increasing year by year, which can affect the quality of life of patients and also increase the economic burden on families and society. The pathogenesis of GERD is still unclear, and some studies suggest that intestinal microecology may be closely related to the development of GERD. Rifaximin is not readily absorbed orally and acts locally in the intestine, so it has mild adverse effects and good safety, and can be used to treat gastrointestinal diseases such as irritable bowel syndrome, traveler’s diarrhea, small intestinal bacterial overgrowth, diverticulosis, inflammatory bowel disease and hepatic encephalopathy. Therefore, this paper focuses on intestinal microecology as a possible pathogenesis of GERD and further explores the feasibility of rifaximin for the treatment of GERD.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82070367).
文摘To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.
基金supported by the Guangxi Science and Technology Project(AD20297088)the National Natural Science Foundation of China(32272316),and the Beijing Innovation Team of Livestock Industry Technology System(BAIC05-2022).
文摘Prenatal overweight/obesity(OW/OB)can alter colostrum lipid patterns,thereby affecting the lipid metabolism and even the cognitive and healthy development of infants.However,studies on changes in colostrum lipids in the context of OW/OB are limited,particularly for glycerides and polar lipids.Therefore,this study investigated the infl uence of maternal prenatal weight on colostrum in lipid subclasses and molecular species.The concentration of triacylglycerols(TAGs)in the colostrum of the OW/OB group(35894.43 mg/L)was higher than that of the normal weight(NW)group(26639.20 mg/L),suggesting that colostrum from OW/OB mothers could provide more energy to their infants.Further analysis of the fatty acid composition of TAGs revealed that elevated maternal body weight enhanced the concentration of TAGs containing saturated or n-6 fatty acids and shortened the carbon number of TAGs.Docosahexaenoic acid(DHA)/arachidonic acid(AA)/choline-containing lipids,such as DHA-containing TAGs,AA/DHA-containing phosphatidylethanolamine,and choline-containing phospholipids,were present in higher levels in the colostrum of OW/OB mothers than NW mothers.However,the concentrations of palmitic acid-containing TAGs,linoleic acid-containing TAGs,dihomo-γ-linolenic acid-containing TAGs,and polar lipids and the ratio of TAGs containing n-6 fatty acid/n-3 fatty acid were signifi cantly higher in the colostrum of OW/OB mothers than in that of NW mothers.The fatty acid composition and sphingoid bases of sphingolipids were also altered due to elevated body weight.In conclusion,OW/OB affects colostrum lipids with respect to composition,concentration,and percentage.Although the colostrum of healthy OW/OB mothers can provide suffi cient DHA/AA/choline-containing lipids to their infants,normalization of body weight and fat reserves should be considered as a strategy for highquality human milk lipids.
基金supported by the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SCMR202103)to Jian LiTibet Autonomous Region Science and Technology Plan(high-tech social development)project(No.XZ202201ZY0031G)to Yang YXAnti-infective Agent Creation Engineering Research Centre of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of pharmacy,Chengdu University(No.AAC2023002)to Lu QX.
文摘Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.
基金supported by the Health Bureau of Jiangsu Province(No.K201104)the Scientific Support Plan of Jiangsu Province(No.BE2011803)+2 种基金the National Natural Science Foundation of China(No.81170102/H0203)the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.BL2012011)the Fourth Period Project"333"of Jiangsu Province(No.BRA2012207),China
文摘Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT （cTns） in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events （MACEs）. Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit （URL） in 133 （13.2%） patients, among which 22 （2.2%） were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 （P = 0.33, 95% CI： 0.74-2.46）. In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.
基金supported by the Science and Technology Support Program of Sichuan Province(No.15ZC1390)National Natural Science Foundation of China(No.41102064)
文摘The Upper Ordovician–Lower Silurian mudstones(including the Wufeng, Guanyinqiao and Longmaxi Formations) in the Sichuan Basin are some of the most important shale gas plays in China. In order to enhance our understanding of the process of formation of organic carbon up to 10%, optical, microscopy and geochemical methods have been used to investigate the petrographic and geochemical characteristics of the formation. Firstly, three mudstone lithofacies were identified based on a wide variety of mudstone laminations. These are:(a) indistinctly laminated mudstone;(b) parallellaminated mudstone; and(c) nonparallel-laminated mudstone. Then, combining with the evidence from depocenter migration, Th/U ratios and total organic carbon, the abundant organo-minerallic fabrics suggest that organic carbon was preferentially deposited and preserved in anoxic, low energy and stagnant water conditions during deposition of the Wufeng and Longmaxi Formations. On the contrary, the Guanyinqiao Formation with poor organic carbon was deposited in oxic and high-energy water conditions.
基金National Natural Science Foundation of China,No.81603574 and No.81774286National Key Research and Development Program,No.2018YFC1704202 and No.2020YFE0201800+1 种基金University Scientific Research Projects of Anhui,No.KJ2020A0401 and No.KJ2019A0442Province Science Foundation of Anhui,No.1708085QH213.
文摘BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.
基金supported by the National Natural Science Foundation of China (No.81830086, 81988101, 81802780)Beijing Municipal Administration of Hospital’s Mission Plan (No.SML20181101)+1 种基金Beijing Nova Program (No.Z191100001119038)Beijing Hospitals Authority Youth Programme (No.QML20191104)。
文摘Objective: Solute carrier family 38(SLC38 s) transporters play important roles in amino acid transportation and signaling transduction. However, their genetic alterations and biological roles in tumors are still largely unclear.This study aimed to elucidate the genetic signatures of SLC38 s transporters and their implications in esophageal squamous cell carcinoma(ESCC).Methods: Analyses on somatic mutation and copy number alterations(CNAs) of SLC38 A3 were performed as described. Immunohistochemistry(IHC) assay and Western blot assay were used to detect the protein expression level. MTS assay, colony formation assay, transwell assay and wound healing assay were used to explore the malignant phenotypes of ESCC cells. Immunofluorescence assay was used to verify the colocalization of two indicated proteins and immunopreciptation assay was performed to confirm the interaction of proteins.Results: Our findings revealed that SLC38 s family was significantly disrupted in ESCC, with high frequent CNAs and few somatic mutations. SLC38 A3 was the most frequent loss gene among them and was linked to poor survival and lymph node metastasis. The expression of SLC38 A3 was lower in tumor tissues compared to that in normal tissues, which was also significantly associated with worse clinical outcome. Further experiments revealed that depletion of SLC38 A3 could promote EMT in ESCC cell lines, and the interaction of SLC38 A3 and SETDB1 might lead to the reduced transcription of Snail. Pharmacogenomic analyses demonstrated that fifteen inhibitors were showed significantly correlated with SLC38 A3 expression.Conclusions: Our investigations have provided insights that SLC38 A3 could act as a suppressor in EMT pathway and serve as a prognostic factor and predictor of differential drug sensitivities in ESCC.
文摘BACKGROUND Warthin’s tumor(WT)is composed of several cysts that are lined with tall,bilayered oncocytic columnar cells and lymphoid stroma.Within WT,the two components rarely transform into carcinoma or lymphoma,and when it does,carcinoma is the most common type.Approximately 28 cases of lymphoma with WT have been reported,most of which were non-Hodgkin lymphomas,and only a few cases were Hodgkin lymphomas.In the present report,we studied a case of diffuse large B cell lymphoma(DLBCL)arising from follicular lymphoma(FL)with WT in the parotid gland and its immunophenotypic and genetic features.CASE SUMMARY A 67-year-old man presented with a slowly enlarging right cheek mass for 12 years,and the mass began to change in size over a 2-mo time period.Over time,the patient felt mild local pain and right cheek discomfort.His medical history included a hepatitis B virus infection for 20 years and 30 years of smoking.Gross examination of the excised specimen showed a gray-red and gray-white appearance and a soft texture lobulated external surface neoplasm that measured 9 cm×8 cm×7 cm and was well circumscribed by relative normal parotid gland tissue.In cross section,the cut surfaces of the neoplasm were multicystic and had a homogeneous scaly appearance.A small fluid was discovered in the cyst.Bilateral oxyphilic,cuboidal or polygonal epithelium cells and lymphoid intraparenchymal components were observed.Many medium-to large-sized lymphoid cells were observed diffusely in part of the neoplasm,and a few secondary lymphoid follicles were observed at the center or edge of the neoplasm.Immunohistochemical staining showed that the columnar oncocytic cells were positive for AE1/AE3;neoplastic cells located in coarctate follicular were positive for CD20,Pax-5,bcl-2 and bcl-6;and the adjacent diffusely medium-to large-sized lymphoid cells were positive for Pax-5,bcl-6,CD20,MUM-1,bcl-2 and CD79a.The bcl-6(3q27)break-apart rearrangement was observed,and an Epstein Barr virus test was negative in the tumor cells.The patient survived 6 months after being diagnosed without any treatment.CONCLUSION WT-associated lymphoma is a very rare neoplasm in the parotid gland.Most cases are B cell non-Hodgkin lymphomas and involve middle-age and older males.This case highlights the extremely rare association of DLBCL arising from FL with WT and the importance of deliberate evaluation of the WT intraparenchymal stroma.Molecular detection techniques have potential advantages in the diagnosis of lymphoma with WT.
文摘A novel electrochemical immunoassay for cardiac troponin Ⅰ （cTnI） combining the concepts of the dual monoclonal antibody ＂sandwich＂ principle, the silver enhancement on the nano-gold particle, and the SBA-15 mesoporous modified carbon paste electrode （SBA-MCPE） is described. Four main steps were carried out to obtain the analytical signal, i.e., electrode preparation, immunoreaction, silver enhancement, and anodic stripping voltammetric detection. A linear relationship between the anodic stripping peak current and concentration of cTnI from 0.5 to 5.0 ng/mL and a limit of detection of 0.2 ng/mL of cTnI were obtained.
文摘Objective: To study the effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells. Methods: Regenerated tissue extracts after liver injury were used to induce SK-HEP1 cells after enrichment, their effects on the proliferation, differentiation, migration and invasion of SK-HEPI cells were observed through in vitro cell culture, MTT, flow cytometry and transwell assays. Results:In response to the action of regenerated tissue extracts after liver injury, SK-HEP1 cells were blocked in G_0/G_1 phase, their growth rate was distinctly reduced. The number of SK-HEP1^(-fj)colonies decreased. The migration ability of SK-HEPI cells showed a decreased trend on day7 and day 11 after induction. SK-HEPl's invasion ability clearly decreased on days 7 and11 after induction, especially on day 7. Conclusions: To a certain extent, regenerated tissue extracts after liver injury can inhibit the proliferation, differentiation, migration and invasion of hepatoma cells, showing an important potential of being a differentiating agent for the treatment of liver cancer.
