Background:Chronic ankle instability(CAI) is a common sequela following an acute lateral ankle sprain(LAS).To treat an acture LAS more effectively and efficiently,it is important to identify patients at substantial ri...Background:Chronic ankle instability(CAI) is a common sequela following an acute lateral ankle sprain(LAS).To treat an acture LAS more effectively and efficiently,it is important to identify patients at substantial risk for developing CAI.This study identifies magnetic resonance imaging(MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients.Methods:All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1,2017 to December 1,2019 were identified.Data were collected using the Cumberland Ankle Instability Tool at final follow-up.Demographic and other related clinical variables,including age,sex,body mass index,and treatment were also recorded.Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS.Results:A total 131 out of 362 patients with a mean follow-up of 3.0± 0.6 years(mean ± SD;2.0—4.1 years) developed CAI after first-episode LAS.According to multivariable regression,development of CAI after first-episode LAS was associated with 5 prognostic factors:age(odds ratio(OR)=0.96,95% confidence interval(95%CI):0.93-1.00,p=0.032);body mass index(OR=1.09,95%CI:1.02-1.17,p=0.009);posterior talofibular ligament injury(OR=2.17,95%CI:1.05-4.48,p=0.035);large bone marrow lesion of the talus(OR=2.69,95%CI:1.30-5.58,p=0.008),and Grade 2 effusion of the tibiotalar joint(OR=2.61,95%CI:1.39-4.89,p=0.003).When patients had at least 1 positive clinical finding in the 10-m walk test,anterior drawer test,or inversion tilt test,they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI.Conclusion:MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the10-m walk test,anterior drawer test,and inversion tilt test.Further prospective and large-scale studies are necessary for validation.展开更多
Nonalcoholic fatty liver disease(NAFLD) is common worldwide.The importance of genetic and epigenetic changes in etiology and pathogenesis of NAFLD has been increasingly recognized.However,the exact mechanism is largel...Nonalcoholic fatty liver disease(NAFLD) is common worldwide.The importance of genetic and epigenetic changes in etiology and pathogenesis of NAFLD has been increasingly recognized.However,the exact mechanism is largely unknown.A large number of single nucleotide polymorphisms(SNPs) related to NAFLD has been documented by candidate gene studies(CGSs).Among these genes,peroxisome proliferatoractivated receptor-γ,adiponectin,leptin and tumor necrosis factor-α were frequently reported.Since the introduction of genome-wide association studies(GWASs),there have been significant advances in our understanding of genomic variations of NAFLD.Patatinlike phospholipase domain containing family member A3(PNPLA3,SNP rs738409,encoding I148M),also termed adiponutrin,has caught most attention.The evidence that PNPLA3 is associated with increased hepatic fat levels and hepatic inflammation has been validated by a series of studies.Epigenetic modification refers to phenotypic changes caused by an adaptive mechanism unrelated to alteration of primary DNA sequences.Epigenetic regulation mainly includes microRNAs(miRs),DNA methylation,histone modifications and ubiquitination,among which miRs are studied most extensively.miRs are small natural single stranded RNA molecules regulating mRNA degradation or translation inhibition,subsequently altering protein expression of target genes.The miR-122,a highly abundant miR accounting for nearly 70% of all miRs in the liver,is significantly under-expressed in NAFLD subjects.Inhibition of miR-122 with an antisense oligonucleotide results in decreased mRNA expression of lipogenic genes and improvement of liver steatosis.The investigation into epigenetic involvement in NAFLD pathogenesis is just at the beginning and needs to be refined.This review summarizes the roles of genetics and epigenetics in the development of NAFLD.The progress made in this field may provide novel diagnostic biomarkers and therapeutic targets for NAFLD management.展开更多
The expression of octamer binding factor 4 (Oct4) gene in bladder cancer cell line T24 and its effects on the biological characteristics of the cells were investigated. RT-PCR and Western blot were employed to detect ...The expression of octamer binding factor 4 (Oct4) gene in bladder cancer cell line T24 and its effects on the biological characteristics of the cells were investigated. RT-PCR and Western blot were employed to detect the expression of Oct4 in T24 cells. The changes of biological charac-teristics in T24 cells were analyzed before and after gene-silencing by Boyden chamber and MTT. The results showed that the expression of Oct4 gene was detectable in T24 cells by RT-PCR and Western blot. The expression of Oct4 gene and protein was down-regulated by siRNA, and average number of transwell cells in interference group, negative control group and blank control group was 101.40±4.56, 104.20±10.03 and 111.00±11.90, respectively. There was significant difference in the proliferation ability of the cells from 48 h, 72 h to 96 h after the interference by siRNA between in-terference group and negative group or blank control group (P<0.05). It was suggested that Oct4 gene was related with proliferation ability of T24 cells, but not with invasive capability.展开更多
Objective: To investigate the effects of neoadjuvant chemotherapy on the expression of drug resistance genes, multidrug resistance-1 (MDR1) and multidrug resistance-associated protein (MRP), in patients with primary b...Objective: To investigate the effects of neoadjuvant chemotherapy on the expression of drug resistance genes, multidrug resistance-1 (MDR1) and multidrug resistance-associated protein (MRP), in patients with primary breast cancer. Methods: MDR1 and MRP expression were detected by semi-quantitative RT-PCR in 20 patients with primary breast cancer, before and after chemotherapy. Results: Before chemotherapy, MDR1 and MRP expression can be detected in 15 cases (75%) and 18 cases (90%) respectively. After chemotherapy, expression of MDR1 is not significantly different from that before chemotherapy, but expression of MRP is significantly different from that before chemotherapy. Conclusion: Expression of drug resistance gene MRP, but not MDR1, is enhanced in patients with primary breast cancer submitted to neoadjuvant chemotherapy.展开更多
Anti-viral chemotherapy plays an important part in treating and preventing influenza illness. However, its effectiveness in severe infections can be debated and a reoccurring problem is the emergence of resistant viru...Anti-viral chemotherapy plays an important part in treating and preventing influenza illness. However, its effectiveness in severe infections can be debated and a reoccurring problem is the emergence of resistant virus. Passive immunisation has for a long time been and is still used for prophylaxis and treatment of a number of infectious diseases. In this experimental study anti-influenza antibodies were passively administrated to mice, subsequently they were infected with influenza virus and treated with oseltamivir. The aim was to investigate, if anti-influenza antibodies influenced the out come of oseltamivir treatment and development of resistance towards oseltamivir. We show, that oseltamivir alone was not able to effectively prevent a fatal outcome, but that oseltamivir administered together with a limited amount of antibodies, resulted in improvement of the clinical condition of the mice. The results also showed that a higher dosage of antibodies alone were able to protect the mice from a lethal dose of virus. These findings suggest that the effectiveness of oseltamivir depends on the host’s immune response to the influenza virus, and that that passive immunization is an option that should be considered in the in control of influenza.展开更多
Using questionnaire is a common, efficient and cheap way to collect data in population-based epidemiological studies. However, there is a general trend of declining response rates leading to a higher risk for bias aff...Using questionnaire is a common, efficient and cheap way to collect data in population-based epidemiological studies. However, there is a general trend of declining response rates leading to a higher risk for bias affecting the validity of results. Use of anonymous questionnaires and/or other ways of distributions, e.g. via schools instead of postal, may increase response rates, but can also lead to other types of systematic errors. This study indicates that results from cross-sectional questionnaire studies differ depending on distribution method and whether the survey is anonymous or not. Also the official purpose of the survey may affect the outcome. When studying well-known risk-factors and health effects, potential methodological problems like reporting bias must be considered in cross sectional studies.展开更多
Coronavirus disease 2019(COVID-19)and helminths infections can be in a synergistic epidemic in developing and suburban areas of industrialized countries.The coinfected hosts will derive a parasite-specific Th2 innate ...Coronavirus disease 2019(COVID-19)and helminths infections can be in a synergistic epidemic in developing and suburban areas of industrialized countries.The coinfected hosts will derive a parasite-specific Th2 innate and adaptive immune response with CD4+T cells,eosinophils,interleukin-4,interleukin-5,and interleukin-10.In the early stages of severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)infection,virus-specific Th1 cytotoxic CD8+T cell,interleukin-6,interferon-γ,and interleukin-27 by lung are keys in controlling viral replication in the lung epithelial cells and limiting the pathology to other organs,like the intestine.CD4+and CD8+T cells are associated with protective immunity against and during COVID-19.However,viral evasion mechanisms occur.Interference of the interferon-γsecretion,like in helminths immunomodulation,can contribute to COVID-19 severity.Immunomodulation can result in mild,moderate,or severe COVID-19 depending on which helminth is coinfecting by regulating or avoiding host cytokine and pro-inflammatory response,decreasing viral load,and affecting vaccine-induced antibody response.We discuss the implications of immunomodulation on COVID-19 caused by helminth co-infection and for public health in the context of COVID-19 vaccine use in helminth endemic zones.展开更多
Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent fa...Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent failure of chemotherapy.To overcome this challenge,amphiphiles(P1)carrying a nitric oxide(NO)donor(Isosorbide 5-mononitrate,ISMN)and high-density disulfide are synthesized for encapsulatingmitochondria-targeted tetravalent platinum prodrug(TPt)to construct a nanocomposite(INP@TPt).Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum,depleting glutathione,and preventing apoptosis escape through generating highly toxic peroxynitrite anion(ONOO−).To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor,an OC patient-derived tumor xenograft(PDXOC)model in BALB/c nude mice was established.INP@TPt showed the best therapeutic effects in the PDXOC model.The corresponding tumor tissues contained high ONOO−levels,which were attributed to the simultaneous release of O_(2)^(·−)and NO in tumor tissues.Taken together,INP@TPtbased systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR,providing practical applications for ovarian therapy.展开更多
BACKGROUND Dexmedetomidine(DMED)is frequently used as a sedative in several medical fields.The benefits of DMED include enhanced quality of regional anesthesia,prolonged analgesia,and postoperative opioid-sparing when...BACKGROUND Dexmedetomidine(DMED)is frequently used as a sedative in several medical fields.The benefits of DMED include enhanced quality of regional anesthesia,prolonged analgesia,and postoperative opioid-sparing when administered intravenously or perineurally in combination with regional anesthesia.Severe hemodynamic complications,such as profound bradycardia and hypotension,can occur after DMED administration in critically ill patients or overdosage;however,there are few reports of complications with DMED administration following brachial plexus block(BPB).CASE SUMMARY We present two cases of hemodynamic instability that occurred following the initial loading of DMED under supraclavicular BPB.A healthy 29-year-old man without any medical history showed profound bradycardia after receiving a loading dose of DMED 0.9μg/kg for 9 min.DMED administration was promptly stopped,and after receiving a second dose of atropine,the heart rate recovered.A 62-year-old woman with a history of cardiomyopathy became hypotensive abruptly,requiring the administration of inotrope and vasopressors after receiving a reduced loading dose of 0.5μg/kg for 10 min.Half of the recommended loading dose of DMED was administered due to the underlying heart dysfunction.Decrea-sed blood pressure was maintained despite the intravenous administration of ephedrine.With continuous infusion of dopamine and norepinephrine,the vital signs were maintained within normal ranges.Inotropic and vasopressor support was required for over 6 h after the initial loading dose of DMED.CONCLUSION DMED administration following BPB could trigger hemodynamic instability in patients with decreased cardiac function as well as in healthy individuals.展开更多
Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective deli...Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.展开更多
The outcome of gallbladder carcinoma is poor,and the overall 5-year survival rate is less than 5%. In early-stage disease,a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There ...The outcome of gallbladder carcinoma is poor,and the overall 5-year survival rate is less than 5%. In early-stage disease,a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma,which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection,primary sclerosing cholangitis,an anomalous junction of the pancreaticobiliary duct,and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However,despite theoretical risk factors,only a third of gallbladder carcinomas are recognized preoperatively. In most patients,the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma''(IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore,the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However,the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry(GR),which records the largest number of incidental gallbladder carcinomas in Europe,indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature,a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1 b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately,there are diverse interpretations and practices regarding stageadjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.展开更多
Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke.Microglial activation and polarization,and the inflammatory response mediated by these cells play important role...Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke.Microglial activation and polarization,and the inflammatory response mediated by these cells play important roles in the development,progression and outcome of brain injury after ischemic stroke.Currently,there is no effective strategy for treating ischemic stroke in clinical practice.Therefore,it is clinically important to study the role and regulation of microglia in stroke.In this review,we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke,with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.展开更多
BACKGROUND Conventional Billroth Ⅱ(BⅡ) anastomosis after laparoscopic distal gastrectomy(LDG) for gastric cancer(GC) is associated with bile reflux gastritis, and Roux-enY anastomosis is associated with Roux-Y stasi...BACKGROUND Conventional Billroth Ⅱ(BⅡ) anastomosis after laparoscopic distal gastrectomy(LDG) for gastric cancer(GC) is associated with bile reflux gastritis, and Roux-enY anastomosis is associated with Roux-Y stasis syndrome(RSS). The uncut Rouxen-Y(URY) gastrojejunostomy reduces these complications by blocking the entry of bile and pancreatic juice into the residual stomach and preserving the impulse originating from the duodenum, while BⅡ with Braun(BB) anastomosis reduces the postoperative biliary reflux without RSS. Therefore, the purpose of this study was to compare the efficacy and safety of laparoscopic URY with BB anastomosis in patients with GC who underwent radical distal gastrectomy.AIM To evaluate the value of URY in patients with GC.METHODS PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database, and VIP Database for Chinese Technical Periodicals(VIP) were used to search relevant studies published from January 1994 to August 18, 2021. The following databases were also used in our search: Clinicaltrials.gov, Data Archiving and Networked Services, the World Health Organization International Clinical Trials Registry Platform Search Portal(https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal), the reference lists of articles and relevant conference proceedings in August 2021. In addition, we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com). We cited highquality references using its results analysis functionality. The methodological quality of the eligible randomized clinical trials(RCTs) was evaluated using the Cochrane Risk of Bias Tool, and the non-RCTs were evaluated using the Newcastle-Ottawa scale. Statistical analyses were performed using Review Manager(Version 5.4).RESULTS Eight studies involving 704 patients were included in this meta-analysis. The incidence of reflux gastritis [odds ratio = 0.07, 95% confidence interval(CI): 0.03-0.19, P < 0.00001] was significantly lower in the URY group than in the BB group. The pH of the postoperative gastric fluid was lower in the URY group than in the BB group at 1 d [mean difference(MD) =-2.03, 95%CI:(-2.73)-(-1.32),P < 0.00001] and 3 d [MD =-2.03, 95%CI:(-2.57)-(-2.03), P < 0.00001] after the operation. However,no significant difference in all the intraoperative outcomes was found between the two groups.CONCLUSION This work suggests that URY is superior to BB in gastrointestinal reconstruction after LDG when considering postoperative outcomes.展开更多
Patients are often nervous prior to surgery and females might suffer the most. Increased nervousness needs attention as it can negatively affect postoperative recovery. Support from nurses, i.e. being present, attenti...Patients are often nervous prior to surgery and females might suffer the most. Increased nervousness needs attention as it can negatively affect postoperative recovery. Support from nurses, i.e. being present, attentive, empowering and helpful to the patient, and talking about what is on the patient’s mind, might help to reduce nervousness. However, there is a lack of evidence as to the ideal level of attention and resources to reduce preoperative nervousness. The objective of the current study was to compare a range of care combinations with standard care to female patients prior to sedation and cancer surgery primarily on difference in change in nervousness from admission until sedation before cancer surgery, measured on a Visual Analouge Scale. Using simple randomization and numbers in sealed envelopes, adult gynaecological patients scheduled for open cancer surgery were allocated to care provided by a nurse anaesthetist and: A) a surgical nurse, B) no additional care, C) a known nurse , and D) a relative. Only the statistician was blinded. The trial stopped when the calculated numbers were included. In the full analysis set, compared to standard care A) (n = 61), we observed the following mean changes and [95% confidence intervals]: B) (n = 65) 1.05 [CI: 0.298 to 1.794] with p = 0.006, C) (n = 61): -0.38 [-1.140 to 0.385] with p = 0.330, D) (n = 71): 0.23 [-0.498 to 0.967] with p = 0.528. Female cancer patients will benefit from supportive care by a surgical nurse from the time of arrival on the operating ward plus supportive care from a nurse anesthetist from 5 - 10 minutes after entering the operating ward. It is not recommended at any time to rely fully on the support of relatives. The effect on adults of preoperative painful procedures and patients’ time alone on the operating ward should be further investigated.展开更多
To date there has been little research that describes the relation between the individual and their environment as the foundation for the coping process in advanced cancer patients. The aim of the study was to identif...To date there has been little research that describes the relation between the individual and their environment as the foundation for the coping process in advanced cancer patients. The aim of the study was to identify and describe, from a patient perspective, processes that are significant to coping with advanced cancer. We used the method Grounded Theory as described by Strauss and Corbin. Data were generated through qualitative interviews. A total of 18 interviews were conducted. The central theme was “The struggle to be a participant in one’s own life”. This theme involved three processes: prioritising, downplaying and self-preservation, each of which in different ways endeavours to either maintain or re-establish the feeling of being a participant. The awareness of the processes complement existing knowledge about coping in advanced cancer patients, by showing how patients make use of meaning-based coping efforts to increase their experience of being a participant in their own lives.展开更多
Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness(IMT) is a strong predictor of myocardial infarction and stroke. Methods and Results-We compared the eff...Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness(IMT) is a strong predictor of myocardial infarction and stroke. Methods and Results-We compared the effects of pioglitazone-based therapy(45 mg/d) and glimepiride-based treatment(2.7± 1.6 mg/d) for 12 and 24 weeks on metabolic control(HbA1c), insulin resistance(homeostasis model assessment), and carotid IMT(B-mode ultrasonography) in a randomized controlled study in 173 orally treated patients with type 2 diabetes(66 women, 107 men; mean± SD age, 62.6± 7.9 years; body mass index, 31.8± 4.6 kg/m2; HbA1c, 7.5± 0.9% ). Treatment was generally well tolerated in both groups. Despite similar improvements in metabolic control(HbA 1c) after 24 weeks(- 0.8± 0.9% [pioglitazone] versus - 0.6± 0.8% [glimepiride]; P=NS), carotid IMT was reduced only in the pioglitazone group after 12 weeks(- 0.033± 0.052 versus- 0.002± 0.047mm[glimepiride]; P< 0.01 between groups) and 24 weeks(- 0.054± 0.059 versus - 0.011± 0.058 mm[glimepiride]; P< 0.005 between groups). Insulin resistance was also improved only in the pioglitazone group(homeostasis model assessment,- 2.2± 3.4 versus- 0.3± 3.3; P< 0.0001 between groups). Reduction of IMT correlated with improvement in insulin resistance(r=0.29, P< 0.0005) and was independent of improvement in glycemic control(r=0.03, P=0.68). Conclusions-We found a substantial regression of carotid IMT, independent of improved glycemic control, after 12 and 24 weeks of pioglitazone treatment. This finding may have important prognostic implications for patients with type 2 diabetes mellitus.展开更多
Aim: To assess the rate of complications following hypospadias repair in a consecutive series of boys and the correlations of those complications with their preoperative symptoms, degree of hypospadias and method of o...Aim: To assess the rate of complications following hypospadias repair in a consecutive series of boys and the correlations of those complications with their preoperative symptoms, degree of hypospadias and method of operation. This study was conducted to address the question of whether all boys with all degrees of hypospadias should undergo reconstruction. Methods: This was a prospective cohort study. We included every boy who underwent an operation for the primary repair of hypospadias between January 2011 and April 2014. The median follow-up time was 24 months. The study ended in October 2014. The main outcome measurements were the frequency of postoperative complications and their correlations with the degree of hypospadias, the preoperative symptoms and the operative intervention performed. Results: Among the 76 boys who underwent operations, 23 had degree 1, 47 had degree 2, and 6 had degree 3 hypospadias. Preoperatively, 43 of the boys had symptoms that motivated the operation, including stenosis (38), a curvature (10) or both (5). Forty-three boys underwent operations with the MAVIS technique, 28 underwent TIP repair, 1 underwent a Duckett procedure, and 4 underwent Byar two-stage procedures. There were complications requiring reoperations including fistulas or ruptures in 26 (34%) boys. There were no significant differences in the rates of complications with surgery, fistulas (P = 0.4775), ruptures (P = 0.2417) or other complications (P = 0.5165) between the groups with or without preoperative symptoms, those with different degrees of hypospadias or those who underwent different operative methods for repair. Conclusions: The complication rate in this series was high. The study was prospective, and no boy was lost during follow-up. Because the complication rate did not correlate with the degree of hypospadias nor the preoperative symptoms, there may be a group of boys with hypospadias without symptoms for whose operations are questionable. The preoperative symptoms should be reported in future reports of the results of hypospadias surgery.展开更多
基金supported by the Biomedicine Supporting Program of Shanghai "Science and Technology Innovation Plan" (19441902400)the Ningxia Hui Autonomous Region Key R&D program (2020BCH01001)+1 种基金the Shanghai "Science and Technology Innovation Action Plan" Domestic Science and Technology Cooperation Project (20025800200)the Clinical Research Program of Shanghai Municipal Health Commission (201940367)。
文摘Background:Chronic ankle instability(CAI) is a common sequela following an acute lateral ankle sprain(LAS).To treat an acture LAS more effectively and efficiently,it is important to identify patients at substantial risk for developing CAI.This study identifies magnetic resonance imaging(MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients.Methods:All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1,2017 to December 1,2019 were identified.Data were collected using the Cumberland Ankle Instability Tool at final follow-up.Demographic and other related clinical variables,including age,sex,body mass index,and treatment were also recorded.Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS.Results:A total 131 out of 362 patients with a mean follow-up of 3.0± 0.6 years(mean ± SD;2.0—4.1 years) developed CAI after first-episode LAS.According to multivariable regression,development of CAI after first-episode LAS was associated with 5 prognostic factors:age(odds ratio(OR)=0.96,95% confidence interval(95%CI):0.93-1.00,p=0.032);body mass index(OR=1.09,95%CI:1.02-1.17,p=0.009);posterior talofibular ligament injury(OR=2.17,95%CI:1.05-4.48,p=0.035);large bone marrow lesion of the talus(OR=2.69,95%CI:1.30-5.58,p=0.008),and Grade 2 effusion of the tibiotalar joint(OR=2.61,95%CI:1.39-4.89,p=0.003).When patients had at least 1 positive clinical finding in the 10-m walk test,anterior drawer test,or inversion tilt test,they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI.Conclusion:MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the10-m walk test,anterior drawer test,and inversion tilt test.Further prospective and large-scale studies are necessary for validation.
基金Supported by The Grants from Guangzhou Municipal Bureau of Health,China,No.2008-Zdi-01 and 2009-ZDi-03
文摘Nonalcoholic fatty liver disease(NAFLD) is common worldwide.The importance of genetic and epigenetic changes in etiology and pathogenesis of NAFLD has been increasingly recognized.However,the exact mechanism is largely unknown.A large number of single nucleotide polymorphisms(SNPs) related to NAFLD has been documented by candidate gene studies(CGSs).Among these genes,peroxisome proliferatoractivated receptor-γ,adiponectin,leptin and tumor necrosis factor-α were frequently reported.Since the introduction of genome-wide association studies(GWASs),there have been significant advances in our understanding of genomic variations of NAFLD.Patatinlike phospholipase domain containing family member A3(PNPLA3,SNP rs738409,encoding I148M),also termed adiponutrin,has caught most attention.The evidence that PNPLA3 is associated with increased hepatic fat levels and hepatic inflammation has been validated by a series of studies.Epigenetic modification refers to phenotypic changes caused by an adaptive mechanism unrelated to alteration of primary DNA sequences.Epigenetic regulation mainly includes microRNAs(miRs),DNA methylation,histone modifications and ubiquitination,among which miRs are studied most extensively.miRs are small natural single stranded RNA molecules regulating mRNA degradation or translation inhibition,subsequently altering protein expression of target genes.The miR-122,a highly abundant miR accounting for nearly 70% of all miRs in the liver,is significantly under-expressed in NAFLD subjects.Inhibition of miR-122 with an antisense oligonucleotide results in decreased mRNA expression of lipogenic genes and improvement of liver steatosis.The investigation into epigenetic involvement in NAFLD pathogenesis is just at the beginning and needs to be refined.This review summarizes the roles of genetics and epigenetics in the development of NAFLD.The progress made in this field may provide novel diagnostic biomarkers and therapeutic targets for NAFLD management.
文摘The expression of octamer binding factor 4 (Oct4) gene in bladder cancer cell line T24 and its effects on the biological characteristics of the cells were investigated. RT-PCR and Western blot were employed to detect the expression of Oct4 in T24 cells. The changes of biological charac-teristics in T24 cells were analyzed before and after gene-silencing by Boyden chamber and MTT. The results showed that the expression of Oct4 gene was detectable in T24 cells by RT-PCR and Western blot. The expression of Oct4 gene and protein was down-regulated by siRNA, and average number of transwell cells in interference group, negative control group and blank control group was 101.40±4.56, 104.20±10.03 and 111.00±11.90, respectively. There was significant difference in the proliferation ability of the cells from 48 h, 72 h to 96 h after the interference by siRNA between in-terference group and negative group or blank control group (P<0.05). It was suggested that Oct4 gene was related with proliferation ability of T24 cells, but not with invasive capability.
文摘Objective: To investigate the effects of neoadjuvant chemotherapy on the expression of drug resistance genes, multidrug resistance-1 (MDR1) and multidrug resistance-associated protein (MRP), in patients with primary breast cancer. Methods: MDR1 and MRP expression were detected by semi-quantitative RT-PCR in 20 patients with primary breast cancer, before and after chemotherapy. Results: Before chemotherapy, MDR1 and MRP expression can be detected in 15 cases (75%) and 18 cases (90%) respectively. After chemotherapy, expression of MDR1 is not significantly different from that before chemotherapy, but expression of MRP is significantly different from that before chemotherapy. Conclusion: Expression of drug resistance gene MRP, but not MDR1, is enhanced in patients with primary breast cancer submitted to neoadjuvant chemotherapy.
文摘Anti-viral chemotherapy plays an important part in treating and preventing influenza illness. However, its effectiveness in severe infections can be debated and a reoccurring problem is the emergence of resistant virus. Passive immunisation has for a long time been and is still used for prophylaxis and treatment of a number of infectious diseases. In this experimental study anti-influenza antibodies were passively administrated to mice, subsequently they were infected with influenza virus and treated with oseltamivir. The aim was to investigate, if anti-influenza antibodies influenced the out come of oseltamivir treatment and development of resistance towards oseltamivir. We show, that oseltamivir alone was not able to effectively prevent a fatal outcome, but that oseltamivir administered together with a limited amount of antibodies, resulted in improvement of the clinical condition of the mice. The results also showed that a higher dosage of antibodies alone were able to protect the mice from a lethal dose of virus. These findings suggest that the effectiveness of oseltamivir depends on the host’s immune response to the influenza virus, and that that passive immunization is an option that should be considered in the in control of influenza.
文摘Using questionnaire is a common, efficient and cheap way to collect data in population-based epidemiological studies. However, there is a general trend of declining response rates leading to a higher risk for bias affecting the validity of results. Use of anonymous questionnaires and/or other ways of distributions, e.g. via schools instead of postal, may increase response rates, but can also lead to other types of systematic errors. This study indicates that results from cross-sectional questionnaire studies differ depending on distribution method and whether the survey is anonymous or not. Also the official purpose of the survey may affect the outcome. When studying well-known risk-factors and health effects, potential methodological problems like reporting bias must be considered in cross sectional studies.
文摘Coronavirus disease 2019(COVID-19)and helminths infections can be in a synergistic epidemic in developing and suburban areas of industrialized countries.The coinfected hosts will derive a parasite-specific Th2 innate and adaptive immune response with CD4+T cells,eosinophils,interleukin-4,interleukin-5,and interleukin-10.In the early stages of severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)infection,virus-specific Th1 cytotoxic CD8+T cell,interleukin-6,interferon-γ,and interleukin-27 by lung are keys in controlling viral replication in the lung epithelial cells and limiting the pathology to other organs,like the intestine.CD4+and CD8+T cells are associated with protective immunity against and during COVID-19.However,viral evasion mechanisms occur.Interference of the interferon-γsecretion,like in helminths immunomodulation,can contribute to COVID-19 severity.Immunomodulation can result in mild,moderate,or severe COVID-19 depending on which helminth is coinfecting by regulating or avoiding host cytokine and pro-inflammatory response,decreasing viral load,and affecting vaccine-induced antibody response.We discuss the implications of immunomodulation on COVID-19 caused by helminth co-infection and for public health in the context of COVID-19 vaccine use in helminth endemic zones.
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515011050)President Foundation of The Third Affiliated Hospital of SouthernMedical University[grant number YM202202].
文摘Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent failure of chemotherapy.To overcome this challenge,amphiphiles(P1)carrying a nitric oxide(NO)donor(Isosorbide 5-mononitrate,ISMN)and high-density disulfide are synthesized for encapsulatingmitochondria-targeted tetravalent platinum prodrug(TPt)to construct a nanocomposite(INP@TPt).Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum,depleting glutathione,and preventing apoptosis escape through generating highly toxic peroxynitrite anion(ONOO−).To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor,an OC patient-derived tumor xenograft(PDXOC)model in BALB/c nude mice was established.INP@TPt showed the best therapeutic effects in the PDXOC model.The corresponding tumor tissues contained high ONOO−levels,which were attributed to the simultaneous release of O_(2)^(·−)and NO in tumor tissues.Taken together,INP@TPtbased systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR,providing practical applications for ovarian therapy.
基金Supported by the Fund of Biomedical Research Institute,Jeonbuk National University Hospital,Jeonju,Republic of Korea.
文摘BACKGROUND Dexmedetomidine(DMED)is frequently used as a sedative in several medical fields.The benefits of DMED include enhanced quality of regional anesthesia,prolonged analgesia,and postoperative opioid-sparing when administered intravenously or perineurally in combination with regional anesthesia.Severe hemodynamic complications,such as profound bradycardia and hypotension,can occur after DMED administration in critically ill patients or overdosage;however,there are few reports of complications with DMED administration following brachial plexus block(BPB).CASE SUMMARY We present two cases of hemodynamic instability that occurred following the initial loading of DMED under supraclavicular BPB.A healthy 29-year-old man without any medical history showed profound bradycardia after receiving a loading dose of DMED 0.9μg/kg for 9 min.DMED administration was promptly stopped,and after receiving a second dose of atropine,the heart rate recovered.A 62-year-old woman with a history of cardiomyopathy became hypotensive abruptly,requiring the administration of inotrope and vasopressors after receiving a reduced loading dose of 0.5μg/kg for 10 min.Half of the recommended loading dose of DMED was administered due to the underlying heart dysfunction.Decrea-sed blood pressure was maintained despite the intravenous administration of ephedrine.With continuous infusion of dopamine and norepinephrine,the vital signs were maintained within normal ranges.Inotropic and vasopressor support was required for over 6 h after the initial loading dose of DMED.CONCLUSION DMED administration following BPB could trigger hemodynamic instability in patients with decreased cardiac function as well as in healthy individuals.
文摘Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.
文摘The outcome of gallbladder carcinoma is poor,and the overall 5-year survival rate is less than 5%. In early-stage disease,a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma,which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection,primary sclerosing cholangitis,an anomalous junction of the pancreaticobiliary duct,and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However,despite theoretical risk factors,only a third of gallbladder carcinomas are recognized preoperatively. In most patients,the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma''(IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore,the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However,the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry(GR),which records the largest number of incidental gallbladder carcinomas in Europe,indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature,a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1 b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately,there are diverse interpretations and practices regarding stageadjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.
基金This work was supported by the National Natural Science Foundation of China,Nos.31871169(to YT),81600040(to APW)Key Project of Department of Education of Hunan Province,China,No.18A243(to APW)+1 种基金Innovation Guidance Project of Hunan Province,China,No.2018SK51606(to SXG)the Natural Science Foundation of Hunan Province of China,No.2017JJ3279(to APW).
文摘Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke.Microglial activation and polarization,and the inflammatory response mediated by these cells play important roles in the development,progression and outcome of brain injury after ischemic stroke.Currently,there is no effective strategy for treating ischemic stroke in clinical practice.Therefore,it is clinically important to study the role and regulation of microglia in stroke.In this review,we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke,with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.
基金Supported by Natural Science Foundation of Gansu Province,China,No.18JR3RA052National Scientific Research Project Cultivation Plan of Gansu Provincial People’s Hospital,No.19SYPYA-1+1 种基金National Key Research and Development Program,No.2018YFC1311506Gansu Province Da Vinci Robot High End Diagnosis and Treatment Personnel Training Project,No.2020RCXM076.
文摘BACKGROUND Conventional Billroth Ⅱ(BⅡ) anastomosis after laparoscopic distal gastrectomy(LDG) for gastric cancer(GC) is associated with bile reflux gastritis, and Roux-enY anastomosis is associated with Roux-Y stasis syndrome(RSS). The uncut Rouxen-Y(URY) gastrojejunostomy reduces these complications by blocking the entry of bile and pancreatic juice into the residual stomach and preserving the impulse originating from the duodenum, while BⅡ with Braun(BB) anastomosis reduces the postoperative biliary reflux without RSS. Therefore, the purpose of this study was to compare the efficacy and safety of laparoscopic URY with BB anastomosis in patients with GC who underwent radical distal gastrectomy.AIM To evaluate the value of URY in patients with GC.METHODS PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database, and VIP Database for Chinese Technical Periodicals(VIP) were used to search relevant studies published from January 1994 to August 18, 2021. The following databases were also used in our search: Clinicaltrials.gov, Data Archiving and Networked Services, the World Health Organization International Clinical Trials Registry Platform Search Portal(https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal), the reference lists of articles and relevant conference proceedings in August 2021. In addition, we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com). We cited highquality references using its results analysis functionality. The methodological quality of the eligible randomized clinical trials(RCTs) was evaluated using the Cochrane Risk of Bias Tool, and the non-RCTs were evaluated using the Newcastle-Ottawa scale. Statistical analyses were performed using Review Manager(Version 5.4).RESULTS Eight studies involving 704 patients were included in this meta-analysis. The incidence of reflux gastritis [odds ratio = 0.07, 95% confidence interval(CI): 0.03-0.19, P < 0.00001] was significantly lower in the URY group than in the BB group. The pH of the postoperative gastric fluid was lower in the URY group than in the BB group at 1 d [mean difference(MD) =-2.03, 95%CI:(-2.73)-(-1.32),P < 0.00001] and 3 d [MD =-2.03, 95%CI:(-2.57)-(-2.03), P < 0.00001] after the operation. However,no significant difference in all the intraoperative outcomes was found between the two groups.CONCLUSION This work suggests that URY is superior to BB in gastrointestinal reconstruction after LDG when considering postoperative outcomes.
文摘Patients are often nervous prior to surgery and females might suffer the most. Increased nervousness needs attention as it can negatively affect postoperative recovery. Support from nurses, i.e. being present, attentive, empowering and helpful to the patient, and talking about what is on the patient’s mind, might help to reduce nervousness. However, there is a lack of evidence as to the ideal level of attention and resources to reduce preoperative nervousness. The objective of the current study was to compare a range of care combinations with standard care to female patients prior to sedation and cancer surgery primarily on difference in change in nervousness from admission until sedation before cancer surgery, measured on a Visual Analouge Scale. Using simple randomization and numbers in sealed envelopes, adult gynaecological patients scheduled for open cancer surgery were allocated to care provided by a nurse anaesthetist and: A) a surgical nurse, B) no additional care, C) a known nurse , and D) a relative. Only the statistician was blinded. The trial stopped when the calculated numbers were included. In the full analysis set, compared to standard care A) (n = 61), we observed the following mean changes and [95% confidence intervals]: B) (n = 65) 1.05 [CI: 0.298 to 1.794] with p = 0.006, C) (n = 61): -0.38 [-1.140 to 0.385] with p = 0.330, D) (n = 71): 0.23 [-0.498 to 0.967] with p = 0.528. Female cancer patients will benefit from supportive care by a surgical nurse from the time of arrival on the operating ward plus supportive care from a nurse anesthetist from 5 - 10 minutes after entering the operating ward. It is not recommended at any time to rely fully on the support of relatives. The effect on adults of preoperative painful procedures and patients’ time alone on the operating ward should be further investigated.
文摘To date there has been little research that describes the relation between the individual and their environment as the foundation for the coping process in advanced cancer patients. The aim of the study was to identify and describe, from a patient perspective, processes that are significant to coping with advanced cancer. We used the method Grounded Theory as described by Strauss and Corbin. Data were generated through qualitative interviews. A total of 18 interviews were conducted. The central theme was “The struggle to be a participant in one’s own life”. This theme involved three processes: prioritising, downplaying and self-preservation, each of which in different ways endeavours to either maintain or re-establish the feeling of being a participant. The awareness of the processes complement existing knowledge about coping in advanced cancer patients, by showing how patients make use of meaning-based coping efforts to increase their experience of being a participant in their own lives.
文摘Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness(IMT) is a strong predictor of myocardial infarction and stroke. Methods and Results-We compared the effects of pioglitazone-based therapy(45 mg/d) and glimepiride-based treatment(2.7± 1.6 mg/d) for 12 and 24 weeks on metabolic control(HbA1c), insulin resistance(homeostasis model assessment), and carotid IMT(B-mode ultrasonography) in a randomized controlled study in 173 orally treated patients with type 2 diabetes(66 women, 107 men; mean± SD age, 62.6± 7.9 years; body mass index, 31.8± 4.6 kg/m2; HbA1c, 7.5± 0.9% ). Treatment was generally well tolerated in both groups. Despite similar improvements in metabolic control(HbA 1c) after 24 weeks(- 0.8± 0.9% [pioglitazone] versus - 0.6± 0.8% [glimepiride]; P=NS), carotid IMT was reduced only in the pioglitazone group after 12 weeks(- 0.033± 0.052 versus- 0.002± 0.047mm[glimepiride]; P< 0.01 between groups) and 24 weeks(- 0.054± 0.059 versus - 0.011± 0.058 mm[glimepiride]; P< 0.005 between groups). Insulin resistance was also improved only in the pioglitazone group(homeostasis model assessment,- 2.2± 3.4 versus- 0.3± 3.3; P< 0.0001 between groups). Reduction of IMT correlated with improvement in insulin resistance(r=0.29, P< 0.0005) and was independent of improvement in glycemic control(r=0.03, P=0.68). Conclusions-We found a substantial regression of carotid IMT, independent of improved glycemic control, after 12 and 24 weeks of pioglitazone treatment. This finding may have important prognostic implications for patients with type 2 diabetes mellitus.
文摘Aim: To assess the rate of complications following hypospadias repair in a consecutive series of boys and the correlations of those complications with their preoperative symptoms, degree of hypospadias and method of operation. This study was conducted to address the question of whether all boys with all degrees of hypospadias should undergo reconstruction. Methods: This was a prospective cohort study. We included every boy who underwent an operation for the primary repair of hypospadias between January 2011 and April 2014. The median follow-up time was 24 months. The study ended in October 2014. The main outcome measurements were the frequency of postoperative complications and their correlations with the degree of hypospadias, the preoperative symptoms and the operative intervention performed. Results: Among the 76 boys who underwent operations, 23 had degree 1, 47 had degree 2, and 6 had degree 3 hypospadias. Preoperatively, 43 of the boys had symptoms that motivated the operation, including stenosis (38), a curvature (10) or both (5). Forty-three boys underwent operations with the MAVIS technique, 28 underwent TIP repair, 1 underwent a Duckett procedure, and 4 underwent Byar two-stage procedures. There were complications requiring reoperations including fistulas or ruptures in 26 (34%) boys. There were no significant differences in the rates of complications with surgery, fistulas (P = 0.4775), ruptures (P = 0.2417) or other complications (P = 0.5165) between the groups with or without preoperative symptoms, those with different degrees of hypospadias or those who underwent different operative methods for repair. Conclusions: The complication rate in this series was high. The study was prospective, and no boy was lost during follow-up. Because the complication rate did not correlate with the degree of hypospadias nor the preoperative symptoms, there may be a group of boys with hypospadias without symptoms for whose operations are questionable. The preoperative symptoms should be reported in future reports of the results of hypospadias surgery.
