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.

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.

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.

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.

Objective:To explore the feature of FOS expression in oxytocin-and vasopressin-positive neurons in the hypothalamic paraventricular nucleus(PVN)under different status of diabetes mellitus(DM).Methods:Intraperito-neal injection of vehicle or STZ in mice was conducted to establish control or diabetes model.Mechanical sensitivity was evaluated by von Frey filament tests to distinguish diabetic neuropathic pain(DNP)from without-pain group(DWP).The expression of FOS,oxytocin(OXT)-and vasopressin(VP)-positive neurons,as well as their double labeling was detected by immunohistochemical and immunofluorescent staining.Cell counting and comparison were made in groups.Results:FOS expression was easily detected in the PVN in the three groups(Control group,DNP group and DWP group)at 7 days,while that in DWP and DNP groups at 28 days was hardly detectable,with the number being signifi-cantly different from the 7 days group(P＜0.05 or 0.001).Likewise,compared with the control group,immunofluo-rescent signals for VP and OXT staining in the DNP and DWP groups also showed a trend of weakening as the modeling time increased(P＜0.05).The cell counting after double staining for VP or OXT with FOS showed that,in the DWP group at 7 days,the number of VP and FOS double-labeled neurons was 74.33±22.10,accounting for(56.64± 7.52)％of VP-positive cells,whereas the double labeling rate for OXT and FOS was only(10.44±3.14)％.In the DNP group at 7 days,the number of OXT and FOS double-labeled neurons was 51.00±31.80,accounting for(18.50 ±9.51)％of OXT-positive neurons,whereas the double labeling rate for VP and FOS was only(9.34±3.27)％.In contrast to these changes in 7 days group,the expression of FOS decreased sharply in the group of 28 days,thereby al-most no double-labeled neurons.Conclusion:The plasticity changes of oxytocin-and vasopressin-positive neurons in the PVN are different depending on the status of pain and non-pain,and the stage of disease progression.Understanding the changes is of great significance for unravelling the neural mechanism of diabetes and its complications.

Background In recent years, Chinese residents have undergone profound changes in dietary habits and lifestyle, and the increasing prevalence rate of central obesity has become one of the major public health problems. Objective To analyze the changes in waist circumference distribution and central obesity prevalence, and the differences by demographic and socioeconomic factors among Chinese adults aged 18-35 in 15 provinces (autonomous regions and municipalities) from 1993 to 2018, and to provide evidence for further exploration of etiology and control measures. Methods Based on the data of nine follow-up rounds of the China Health and Nutrition Survey from 1993 to 2018, adults aged 18 to 35 were selected as study subjects. After excluding the records of missing demographic information or abnormal physical measurement data, a total of 16008 subjects were included in this study. Central obesity was diagnosed by WS/T 428—2013 Criteria of weight for adults. Spearman rank test was used to analyze the changes of waist circumference; Cochran-Armitage trend test was used to analyze the trends of central obesity prevalence rate; multiple logistic regression analysis was used to analyze the influencing factors of central obesity in the whole population; subgroup analysis on waist circumference and central obesity prevalence rate was also conducted among participants from the 2018 follow-up survey. survey. Results From 1993 to 2018, the waist circumference and prevalence rate of central obesity of adults aged 18-35 in 15 provinces (autonomous regions and municipalities) significantly increased by year (P<0.05). In males, the prevalence rate increased from 4.40% to 35.49% (P_trend<0.05), while in females, it increased from 6.33% to 18.31% (P_trend<0.05), and the average growth rates were 8.14% and 2.58% per annum, respectively. The results of multiple model analysis showed that subjects aged 25 to 35 years were more likely to have central obesity than the control group with age 18 to 24 years in both males (OR=1.285, 95%CI: 1.066-1.550) and females (OR=1.558, 95%CI: 1.234-1.967). There were significant associations of central obesity in males with residence, geographical location, and economic zones: urban males were 39.5% (OR=1.395, 95%CI: 1.169-1.165) more likely to suffer from central obesity than rural males; males living in southern China were 37.9% (OR=0.621, 95%CI: 0.519-0.744) less likely to suffer from central obesity than those living in northern China; compared with males living in central economic zone, males living in western economic zone were 27.1% (OR=0.729, 95%CI: 0.567-0.937) less likely and males living in eastern economic zone were 21.8% (OR=1.218, 95%CI: 1.017-1.459) more likely to suffer from central obesity. No significant correlation was found of residence and geographical location with central obesity in females, only in the western economic zone, females were 32.4% (OR=0.676, 95%CI: 0.515-0.886) less likely to suffer from central obesity than those in the central economic zone. With increase of income levels, females were less likely to be central obese, and females of middle income level (OR=0.749, 95%CI: 0.600-0.934) and high income level (OR=0.684, 95%CI: 0.542-0.864) were less likely to suffer from central obesity than those of low income level. In the total population, a higher body mass index (BMI) level was significantly associated with having central obesity; overweight and obese males were found to be 12.207 (95%CI: 10.228-14.568) and 150.418 (95%CI: 111.186-203.492) times more likely to have central obesity, respectively, and the odds ratios for females were 9.014 (95%CI: 7.446-10.912) and 88.215 (95%CI: 61.411-126.717), respectively. Conclusion From 1993 to 2018, waist circumference and the prevalence rate of central obesity in adults aged 18-35 in selected 15 provinces (autonomous regions and municipalities) of China have been increased year by year, the condition of central obesity is more severe in males. Gender, age, economic zones, and BMI are the major influencing factors. It is necessary to take effective early screening and intervention measures targeting central obesity in youth population to reduce health risks.

Background China is witnessing an accelerated aging process and an increasingly serious situation of Parkinson's disease. Research on the pre-disease stage and its related influencing factors has gained more and more attention. Objective To analyze the current situation of prodromal Parkinson's disease (pPD) of people aged 55 years and above in four provinces of China, and to explore its influencing demographic and socio-economic characteristics. Methods Using the data of Community-based Cohort Study on Nervous System Disease in 2020, a total of 10724 participants with complete data on demographic and socio-economic factors and risk factors on Parkinson's disease were selected. Based on the criteria recommended by the International Parkinson and Movement Disorder Society (MDS), we evaluated risk level (i.e., post-test probability) of pPd, prevalence of possible or probable pPD, and number of pPD-related risk/prodromal markers in the participants. Multiple linear regression and multiple logistic regression models were used to analyze the influencing socio-demographic factors of risk level of pPd and prevalence of possible or probable pPD, and Poisson regression and multinomial logit regression models were used to analyze the influencing socio-demographic factors of the number of pPD-related risk/prodromal markers in the total sample, men, and women, respectively. Results The median (P₂₅, P₇₅) of post-test probability of pPD in 2020 was 0.78% (0.42%, 1.66%), the prevalence rate of possible or probable pPD was 0.34%, and 69.03% of the participants reported 3-5 pPD-related risk/prodromal markers. The post-test probabilities of men, those with older age, lower education level, per capita monthly household income < 1000 yuan, urban residency, or without active employment were higher (P<0.05). Men and being aged ≥ 75 years had a higher prevalence of possible or probable pPD (P<0.05). The OR of possible or probable pPD was 8.404 (95%CI: 2.839−24.879) in subjects aged ≥ 75 years versus those aged 55−64 years. Males, those without active employment, being less educated, with older age, and urban residents were more likely to report pPD-related risk/prodromal markers than those of the opposite groups (P<0.05). Conclusion Men, subjects aged ≥75 years, those with lower education level, urban residents, and those without active employment have higher risk levels of pPD and are more likely to report pPD-related risk/prodromal markers among people aged 55 years and above in the four provinces of China, poor economic situation is also associated with higher risk levels of pPD.