Aim To investigate the effects and signifi-cance of 5-HT2A receptor antagonist MDL1 1 939 on a-mice.Methods Kunming male mice were suffered a-cute acetic acid visceral pain,acute incision pain and CCI neuropathic pain.After each animal model was es-tablished,MDL1 1 939 was injected intraperitoneally. The writhing reaction was used to assess acute acetic acid visceral pain,while the thermal withdrawal laten-cy (TWL)was used to evaluate the acute incision pain and CCI neuropathic pain.Results Compared with the control group,MDL1 1 939 (0.25,0.5,1 .0 mg· kg -1 ,i.p.)relieved acetic acid visceral pain signifi-cantly in a dose-dependent manner in mice,as re-vealed by the significant reduction of the number of twisting.In acute incision pain and CCI neuropathic pain,MDL1 1 939 (0.5 mg·kg -1 ,i.p.)significantly increased TWL level.Conclusion 5-HT2A receptor antagonist MDL1 1 939 has analgesic effects on visceral pain,acute pain and neuropathic pain,which might be a novel therapeutic target to treat different pain in clini-cal situations.

Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1),ATP-binding cassette C2 (ABCC2) and solute carrier organic anion transporter 1B1 (SLCO1 B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL).Methods This study was designed as a casecontrol.From September of 2005 to December of 2011,the blood samples were randomly collected from 142ALL patients from Nanjing Children's Hospital,Enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX,Seven SNPs in ABCB1 (rs1045642,rs2032582,rs1128503),ABCC2 (rs717620,rs2273697) and SLCO1 B1 (rs4149081,rs11045879) genes were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR).Results A significantly increased risk of MTX-induced toxicity was observed in patients with MTX elimination delay (OR ＝ 2.828,95％ CI:1.217-6.571,P ＜ 0.05).Two SNPs in SLCO1B1,rs4149081 and rs11045879 were linkage disequilibrium (LD) with each other (R2 =0.979,P ＜ 0.05).Multivariate analysis revealed that individuals with SLCO1B1 rs4149081 AA genotype or SLCO1B1 rs11045879 CC genotype showed increased incidence of MTX elimination delay (OR =4.41,95％ CI:1.537-12.654,P =0.042),and the two genotypes were also associated with significantly increased risk of MTX-induced toxicity (OR =4.118,95％ CI:1.135-14.944,P =0.022).No association of MTX elimination delay or MTX-induced toxicity with the other SNPs analyzed was found.Conclusions SLCO1B1 rs4149081 AA or SLCO1B1 rs11045879 CC genotypes might be a risk factor for the susceptibility to MTX-induced toxicity in children with ALL.

Aim To explore the effect of activated SK channels(small conductance Ca2+-activated K+ channels) on morphine-induced hyperalgesia in the spinal cord in mice.Methods Adult C57BL6/N male mice were chosen to establish the model of morphine-hyperalgesia.The changes of tail withdrawal latency(TWL), mechanical withdrawal threshold(MWT) and the threshold of visceral pain were observed after intrathecal 1-EBIO, the agonist of SK channels.Results Compared with the control group, TWL, MWT and the threshold of visceral pain were decreased after morphine injection.After intrathecal 1-EBIO, the TWL, MWT and visceral pain threshold were increased.The level of spinal membrane SK2 expression in morphine-treated mice was decreased compared with that of control group.After intrathecal 1-EBIO, the level of spinal membrane SK2 expression was increased.Conclusion SK channels in the spinal cord are involved in morphine-induced hyperalgesia in mice.

Objective To investigate the influences of the functional polymorphisms of cytochrome P450 isozymes 2A6 (CYP2A6),2B6 (CYP2B6),2C9 (CYP2C9),and 2C19 (CYP2C19) on plasma concentration of sodium valproate.Methods A total of 131 Chinese children with epilepsy receiving sodium valproate after a period of more than 5 half-time were recruited.The genotypes of CYP2A6 were detected by multiplex polymerase chain reaction (PCR),and the genotypes of CYP2B6,CYP2C9,and CYP2C19 were detected by PCR-ligase detection reaction.Enzyme-multiplied immunoassay technique was used to measure the plasma concentration of sodium valproate.The association between the polymorphisms and the plasma concentration of sodium valproate were analyzed by one-way ANOVA or Student' s t-test.Results Patients were divided into 4 groups according to the genotyping results of CYP2C9 and CYP2C19 (G1:extensive metabolizers in both CYP2C9 and CYP2C19; G2:CYP2C19 intermediate metabolizers; G3:CYP2C19 poor metabolizers; G4:CYP2C9 poor metabolizers),the mean normalized steady-state sodium valproate concentrations were significantly higher in G3 (3.70 ± 0.95) and G4 (4.35 ± 1.48) patients when compared to those in G 1 (2.57 ± 1.30,t =3.056,4.490,both P ＜ 0.01) and G2 (2.76 ± 1.19,t =2.827,4.462,both P ＜ 0.01) patients.The daily doses (mg/d) of sodium valproate received by G3 (19.46 ± 5.20) and G4 (19.30 ±7.67) patients were significantly lower than that of G1 patients(24.10 ±6.97,t =2.359,2.297,both P ＜ 0.05).There were no differences in daily doses or normalized steady-state concentrations of sodium valproate among the CYP2A6* 4 or CYP2B6* 6 genotypic groups.Conclusions The CYP2C9 and CYP2C19 polymorphisms have dramatic effects on the plasma concentration of sodium valproate.The daily doses of sodium valproate in G3 and G4 patients should be lower than usual.

Objective:To establish a new model for the prediction of severe outcomes of COVID-19 patients and provide more comprehensive, accurate and timely indicators for the early identification of severe COVID-19 patients.Methods:Based on the patients’ admission detection indicators, mild or severe status of COVID-19, and dynamic changes in admission indicators (the differences between indicators of two measurements) and other input variables, XGBoost method was applied to establish a prediction model to evaluate the risk of severe outcomes of the COVID-19 patients after admission. Follow up was done for the selected patients from admission to discharge, and their outcomes were observed to evaluate the predicted results of this model.Results:In the training set of 100 COVID-19 patients, six predictors with higher scores were screened and a prediction model was established. The high-risk range of the predictor variables was calculated as: blood oxygen saturation <94 %, peripheral white blood cells count >8.0×10 9, change in systolic blood pressure <-2.5 mmHg, heart rate >90 beats/min, multiple small patchy shadows, age >30 years, and change in heart rate <12.5 beats/min. The prediction sensitivity of the model based on the training set was 61.7 %, and the missed diagnosis rate was 38.3 %. The prediction sensitivity of the model based on the test set was 75.0 %, and the missed diagnosis rate was 25.0 %. Conclusions:Compared with the traditional prediction (i.e. using indicators from the first test at admission and the critical admission conditions to assess whether patients are in mild or severe status), the new model’s prediction additionally takes into account of the baseline physiological indicators and dynamic changes of COVID-19 patients, so it can predict the risk of severe outcomes in COVID-19 patients more comprehensively and accurately to reduce the missed diagnosis of severe COVID-19.

In order to meet the needs of contemporary society for medicine and cultivate high-quality compound medical talents, Chongqing Medical University has carried out the "organ system-centered" urogenital system integration curriculum reform. In the practice of integrated curriculum teaching, students have deepened their systematic understanding of medical knowledge, enhanced their enthusiasm and initiative in classroom learning, cultivated students' logical thinking ability, and improved students' innovative scientific research ability, by reorganizing the curriculum system, rewriting textbooks, improving the teaching environment, forming a teaching team, and reforming teaching methods, which laids the foundation for the further improvement of the medical curriculum.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objective To establish the reference intervals for test indicators of thyroid function,namely thyroid stimulating hormone(TSH),free thyroxine(FT4),and free triiodothyronine(FT3),in the children aged 0 to 15 years old in Nanning,China.Methods A total of 1 289 healthy children aged 0 to 15 years old who attended the Guangxi International Zhuang Medicine Hospital Affiliated with Guangxi University of Chinese Medicine from October 2018 to August 2023 were selected.The concentrations in serum TSH,FT4,and FT3 were measured by chemiluminescent microparticle immunoassay(CMIA).According to the Clinical and Laboratory Standards Institute(CLSI)EP28-A3c guideline,the nonparametric percentile method was used to establish the reference intervals for TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area.Results The established reference intervals were as follows:TSH(male):0 to＜1 month:0.88-7.81 μIU/mL,1 month to 15 years:0.59-5.06 μIU/mL;TSH(female):0 to＜1 month:0.93-8.42μIU/mL,1 month to 15 years:0.60-4.30 μIU/mL.FT4(male):0 to＜1 month:0.99-1.92 pg/mL,1 month to 15 years:0.86-1.33 pg/mL;FT4(female):0 to＜1 month:1.05-2.06 pg/mL,1 month to 15 years:0.85-1.37 pg/mL;FT3:0 to＜1 month:2.16-4.24 pmol/L,1 month to＜11 years:2.75-4.49 pmol/L,11 to 15 years:2.45-4.34 pmol/L.Significant differences were observed among different gender and age groups for TSH,FT4,and FT3 levels(P＜0.05).Conclusion This study successfully established the refer-ence intervals of TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area,which were significantly different among various gender and age groups.

Objective:To retrieve, evaluate, and summarize the best evidence for peripherally inserted central catheter (PICC) related thrombosis in children.Methods:Guideline websites, relevant society websites, and databases at China and abroad were searched for guidelines, evidence summaries, expert consensuses, and systematic reviews related to thrombosis before and after PICC catheterization in children published up to June 30, 2021 based on evidence-based nursing. The quality of the literature was independently evaluated by 2 researchers with reference to Appraisal of Guidelines for Research and Evaluation InstrumentⅡ and the criteria of the Joanna Briggs Institute (JBI) in Australia (2016) . Data were extracted from the literatures that met the standards through expert demonstration, and the evidence was graded and recommended according to the JBI evidence pre-grading system (2014 edition) .Results:A total of 11 articles were included, including 4 guidelines, 1 systematic review, 1 expert consensus, and 5 evidence summaries. 27 pieces of evidence were summarized from 7 aspects: organizational management, catheter selection, blood vessel selection and puncture, location of catheter tip, physical prevention, drug prevention, and evaluation.Conclusions:This paper summarizes and analyzes the best evidence for PICC-related thrombosis in children and provides an evidence-based reference for the clinical application and practice of PICC-related thrombosis in children.

With the expansion of aging population in China, the increasingly serious situation of Parkinson's disease (PD) threatens the physical and mental health and quality of life of middle-aged and elderly people, posing a great challenge to increase healthy life expectancy and realize the Healthy China Strategy. Previous studies showed some connections between dietary and lifestyle factors and PD and suggested that excessive intake of red meat might increase the risk of PD; however, coffee and tea, dietary antioxidants, n-3 polyunsaturated fatty acids, vitamin D, and vitamin B were associated with reducing the risk of PD or delaying the progression of PD, and dietary patterns with high intakes of fresh vegetables and fruits, legumes, whole grains, fish, and poultry meat were also associated with a reduced risk of PD. In addition, physical activity was a protective factor for PD, and smoking was also associated with a reduced risk of PD, but the related mechanisms were still unclear. This paper evaluated the relationships of factors like foods, nutrients, dietary patterns, and lifestyle with PD based on published literature, summarized the limitations of relevant studies, and provided useful enlightenment for PD prevention and control.