1.Ethical Thoughts on the Quality Evaluation of the Kidneys from Expanded Criteria Donors
Feng NIE ; Chen HUANG ; Qing TAN ; Yun HU
Chinese Medical Ethics 2024;35(4):386-390
In the case of extremely shortage of donor kidney sources, the number of Expanded Criteria Donors (ECD) with relatively poor kidney quality and transplantation effect is increasing. In order to alleviate the contradiction between supply and demand by using transplantable kidneys as much as possible and avoid the failure or poor effect of transplantation caused by poor quality kidneys, the quality assessment and evaluation criteria of ECD kidney have become a research hotspot in the field of kidney transplantation. This paper analyzed the possible ethical defects in the research process, and put forward some suggestions for the transplantation team to strictly follow the ethical principles of "no harm", "beneficial" and "informed consent", and the organ transplantation ethics committee to pay attention to the ethical review of the quality evaluation process of ECD donor kidney.
2.The Application of Bacterial Outer Membrane Vesicles in Tumor Treatment
Yun-Feng WANG ; Wan-Ru ZHUANG ; Xian-Bin MA ; Wei-Dong NIE ; Hai-Yan XIE
Progress in Biochemistry and Biophysics 2024;51(2):309-327
Outer membrane vesicles (OMVs) are nanoscale vesicles secreted by Gram-negative bacteria. As a unique bacterial secretion, OMV secretion can help bacteria maintain the outer membrane stability or remove harmful substances. Studies have shown that local separation of outer membrane and peptidoglycan layers led by abnormalities in outer membrane protein function, abnormal structure or excessive accumulation of LPS, and erroneous accumulation of phospholipids in the outer leaflet, which can all lead to bacterial outer membrane protrusion and eventually bud formation of OMVs. Since OMVs are mainly composed of bacterial outer membrane and periplasmic components, the pathogen associated molecular patterns (PAMPs) on their surface can trigger strong immune responses. For example, OMVs can recruit and activate neutrophils, polarize macrophages to secrete large amounts of inflammatory factors. More importantly, OMVs can act as adjuvants to induce dendritic cell (DC) maturation to enhance adaptive immune response in the body. At the same time, OMVs are derived from bacteria, which make it easy to modify. The methods by genetic engineering and others can improve their tumor targeting, give them new functions, or reduce their immunotoxicity, which is conducive to their application in tumor therapy. OMVs not only induce apoptosis or pyroptosis of tumor cells, but also regulate the host immune system, which makes OMVs themselves have a certain killing effect on tumors. In addition, the tendency of neutrophils to inflammatory tumor sites and the formation of neutrophil extracellular traps enable OMVs to target tumor sites, and the suitable size and the characteristic that they are easily taken up by DCs give OMVs a certain lymphatic targeting ability. Therefore, OMVs are often employed as excellent drug or vaccine carriers in tumor therapy. This review mainly discusses the biological mechanism of OMVs, the regulatory effects of OMVs on immune cells, the functional modification strategies of OMVs, and their research progress in tumor therapy.
3.Effects and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats
Dong AN ; Yong-Lin LIANG ; Yan-Kui GAO ; Feng-Zhe YAN ; Min BAI ; Si-Chen ZHAO ; Zhong-Tang LIU ; Xiao NIE
The Chinese Journal of Clinical Pharmacology 2024;40(9):1282-1286
Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P<0.01,P<0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.
4.Effects of quercetin combined with iron death inhibitor on calcium oxalate-induced HK-2 cell damage
Bing-Fei NIE ; Huang-Hui CHEN ; Qun-Jie TAN ; Yu-Feng DU
The Chinese Journal of Clinical Pharmacology 2024;40(14):2028-2032
Objective To explore the effect of quercetin combined with iron death inhibitor Ferrostain-1 on oxalate-induced HK-2 cell injury.Methods HK-2 cells were randomly divided into control group(normal cultured cells),model group(0.5 mmol·L-1 calcium oxalate crystals),quercetin group(0.5 mmol·L-1 calcium oxalate crystals+100 μmol·L-1 quercetin),inhibitor group(0.5 mmol·L-1 calcium oxalate crystals+8 μmol·L-1 Ferrostain-1)and combination group(0.5 mmol·L-1calcium oxalate crystals+100 μmol·L-1quercetin+8 μmol·L-1 Ferrostain-1).Cell counting kit-8(CCK-8)assay was used to detect cell survival rate;Western blot was used to detect iron death related protein expression such as glutathione peroxidase 4(GPX4);flow cytometry and Tunel assay were used to detect cell apoptosis,and assay kit was used to detect cellular iron ions and antioxidant levels.Results The cell survival rates of control group,model group,quercetin group,inhibitor group and combination group were(100.00±2.55)%,(54.49±4.11)%,(64.26±6.30)%,(58.03±3.04)%and(79.37±4.29)%,respectively;GPX4 protein expression levels were 0.98±0.11,0.33±0.05,0.56±0.05,0.78±0.07 and 1.11±0.11,respectively;cell apoptosis rates were(4.15±0.28)%,(23.12±2.49)%,(17.28±1.07)%,(15.08±1.41)%and(8.95±0.75)%,respectively;Fe2+levels were(100.00±0.87)%,(162.55±14.70)%,(149.09±9.50)%,(144.95±11.12)%and(131.76±12.18)%,respectively;superoxide dismutase(SOD)levels were(58.67±3.46),(21.56±1.32),(33.60±2.03),(35.15±3.02)and(44.27±3.89)U·mL-1,respectively.The above indicators of the model group were compared with the control group,and the above indicators of the quercetin group,inhibitor group,and combination group were compared with the model group,the above indicators of the combination group were compared with the quercetin group,and inhibitor group,all they all showed statistical significance(all P<0.05).Conclusion Iron death inhibitors can enhance the inhibitory effect of quercetin in vitro on oxalate-induced renal tubular epithelial cell injury.
5.Clinical trial of nintedanib combined with tetrandrine in the treatment of patients with connective tissue disease-related pulmonary interstitial fibrosis
Dong-Ming YANG ; Jian-Jun NIE ; Wei REN ; Rui ZHANG ; Ben-Shang GONG ; Dong-Feng XU
The Chinese Journal of Clinical Pharmacology 2024;40(19):2781-2785
Objective To observe the influence of nintedanib ethanesulfonate soft capsules combined with tetrandrine tablets on pulmonary function and dyspnea symptoms in patients with connective tissue disease-related pulmonary interstitial fibrosis.Methods Patients with connective tissue disease-related pulmonary interstitial fibrosis were divided into treatment group and control group by cohort method.The control group was given basic treatment such as glucocorticoids and immunosuppressants according to the patient's condition;the treatment group was given ethanesulfonate nintedanib soft capsules(100 mg,bid)and tetrandrine tablets(40 mg,tid)on the basis of the control group,and the treatment course was 3 months.The clinical efficacy,severity of dyspnea[modified British Medical Research Council Dyspnea Scale(mMRC)and St.George's Respiratory Questionnaire(SGRQ)],pulmonary function indicators,pulmonary fibrosis score,and blood gas analysis indicators were compared between the two groups,and the safety was assessed.Results A total of 42 cases were included in the treatment group and the control group,respectively.The total effective rates of the treatment group and the control group were 92.86%(39 cases/42 cases)and 76.19%(32 cases/42 cases)respectively(P<0.05).After treatment,the mMRC scores of the treatment group and the control group were(1.43±0.27)and(1.69±0.31)points;the SGRQ scores were(46.51±4.39)and(51.08±4.76)points;the forced expiratory volume in one second(FEV1)values were(64.96±6.55)%and(58.67±5.01)%;the fibrosis scores were(1.12±0.14)and(1.26±0.18)points;the partial pressure of arterial oxygen values were(80.31±7.03)and(75.02±6.94)mmHg.The above indexes of the treatment group were compared with those of the control group,and the differences were statistically significant(all P<0.05).There were no adverse drug reactions in the treatment group,and the main adverse drug reactions in the control group were gastrointestinal discomfort.The total incidence rates of adverse drug reactions in the treatment group and the control group were 0 and 2.38%,respectively(P>0.05).Conclusion Compared with basic treatment,nintedanib ethanesulfonate soft capsules combined with tetrandrine tablets can better improve the pulmonary fibrosis degree and dyspnea degree in patients with connective tissue disease-related pulmonary interstitial fibrosis,and delay the decline of pulmonary function of patients.
6.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
7.Value of endoscopic retrograde cholangiopancreatography for the diagnosis and treatment of pediatric pancreaticobiliary maljunction
Shuang NIE ; Hao ZHU ; Shanshan SHEN ; Wen LI ; Wei CAI ; Zhengyan QIN ; Feng LIU ; Bin ZHANG ; Yuling YAO ; Lei WANG ; Xiaoping ZOU
Chinese Journal of Digestive Endoscopy 2024;41(2):137-141
Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.
8.Application Strategy of Toxic Chinese Materia Medica Based on the Theory of “Heterogeneous Medicinals Mutual Restriction”
Xueping ZHOU ; Zhe FENG ; Zhichao YU ; Weijue NIE
Journal of Traditional Chinese Medicine 2024;65(5):449-454
Toxic Chinese materia medica has been highly valued by its specialized and effective effects, but its safe application has become an urgent clinical problem to be solved. Compatibility for toxic attenuation is an important method for the rational clinical application of toxic Chinese materia medica as well as the promotion of its therapeutic advantages. The theory of “heterogeneous medicinals mutual restriction” elaborated in this article has been formed through long-term clinical practice and cognition, and refinement of clinical experience, which means that the nature partiality of toxic Chinese materia medica can be adjusted, and the toxicity can be suppressed through reasonable combination with herbal medicinalsof different properties, flavors, and effects. This theory covers the modes of compatibility for toxicity attenuation and the interaction relationships, like the restriction of medicinals with different properties and flavors, restriction of medicinals with different effects, and inhibiting toxins by reinforcing healthy qi. The opposite and complementary effects of various medicinals combinations are an extension of the connotations of this theory, and the principles can be explained from material basis and mechanism of action. Under the guidance of this theory, it is possible to optimize the compound prescription strategies of toxic Chinese materia medica, and provide new strategies for the clinical combinations of toxic Chinese materia medica, thereby achieving the reduction of toxicity and enhancement of effectiveness of the compound formulas.
9.Research progress of molecular docking in screening anti-cervical cancer drugs
Dan WANG ; Wenyan ZHANG ; Renjie LUO ; Yuanjing CHEN ; Xue HAN ; Bo QU ; Shifang FENG ; Xiazi NIE ; Huiling LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(8):955-960
Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metasta-sis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs,finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs.This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.
10.Salmonella infection and drug resistance in foodborne disease surveillance among children in Wuhan from 2017 to 2022
Li NIE ; Ying DENG ; Wan-Jun LUO ; Feng TANG
Chinese Journal of Zoonoses 2024;40(8):750-757
This study was aimed at analyzing the Salmonella infection rate,serotype distribution,and drug resistance rate among children with foodborne diseases in Wuhan,to provide evidence for the prevention and control of foodborne diseases in children.We collected pediatric cases of foodborne diseases and fecal specimens in Wuhan from 2017 to 2022,and conducted statistical analysis in SPSS 22.0.A total of 1 180 cases of foodborne diseases in children were monitored,and 281 strains of Salmonella were detected.Salmonella was distributed across 27 serotypes,primarily Salmonella enteritidis(138 strains,ac-counting for 49.11%)and Salmonella typhimurium(37 strains,accounting for 13.17%).The Salmonella-positive cases in-cluded more boys than girls(1.58∶1 ratio),and the age group with the highest detection rate was 7-18 years(34.48%).The proportion of positive patients gradually decreased,and the detection rate gradually increased,with increasing age.Milk and dairy products,fruits and fruit products,and grain and grain products were the main suspected food exposures with high Sal-monella detection rates.The Salmonella detection rate was highest in the third quarter(44.64%),and significant differences were observed in the positivity rates of Salmonella samples across seasons(x2=178.483,P<0.05).The main clinical mani-festations of children with Salmonella infection were fever(87.19%)and diarrhea(96.44%),primarily watery stool(51.96%).Salmonella showed different degrees of resistance to 14 antibiotics(1.08%-75.99%),primarily ampicillin(75.99%),tetracycline(68.10%),and cefazolin(50.18%).A significant seasonal pattern was observed in the detection of Sal-monella in foodborne diseases among children in Wuhan,and in various suspected food exposures.The serotype composition was polymorphic,and the Salmonella resistance rate was relatively high.Therefore,active monitoring of foodborne diseases and Salmonella resistance surveillance must continue to be strengthened.

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