OBJECTIVE To investigate the application status of prescription pre-review systems in healthcare institutions of Yunnan province， evaluate their system functions and management capabilities， and provide a practical basis for promoting rational drug use. METHODS A questionnaire survey was conducted among public healthcare institutions at or above the secondary level in Yunnan province to investigate the deployment status of the systems. A capability maturity assessment framework was constructed， encompassing 6 dimensions and 39 indicators， including real-time prescription review， prescription correlation review， rule setting， evidence-based information support， prescription authority management， and system operation management. This framework was then used to evaluate the institutions that had implemented the pre-review systems. RESULTS A total of 100 valid questionnaires were collected， with 37 institutions having adopted prescription pre-review systems， mainly tertiary hospitals. The system predominantly adopted a modular architecture and was embedded into the hospital information system through application programming interfaces and middleware， providing certain capabilities for real-time prescription risk identification. Evaluation results indicated that basic functions such as reviewing indications， contraindications， and drug compatibility performed well， while deficiencies remained in functions related to parenteral nutrition prescription， review of drug dosage for specific diseases， individual patient characteristic recognition， and rule setting. Moreover， the construction of review centers and establishment of management systems were also not well-developed. CONCLUSIONS The overall application rate of prescription pre-review systems in Yunnan province remains low. System functions and management mechanisms require further improvement. It is recommended to enhance information infrastructure in lower-level institutions and explore regionally unified review models to promote standardized and intelligent development of prescription review practices.

Objective:Biological markers of the ventrolateral orbitofrontal cortex(vlOFC)involved in pain regula-tion were screened.Methods:Chronic inflammatory pain was induced in male C57BL/6J mice by injection of complete Freund's adjuvant(CFA)into the left posterior plantar.Paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were detected to evalue hyperalgesia.Transcriptome sequencing was performed on fresh tissue from vlOFC of mice after behavioral tests.The differentially expressed genes(DEGs)were screened by bioinformatics method,and their biological functions and pathways were enriched.Results:Compared with the PBS group,the left hindpaw me-chanical pain threshold and the paw withdrawal latency caused by heat pain were significantly reduced in the CFA group(P＜0.001).The DEGs of vlOFC in the two groups were 497,of which 143 were up-regulated and 354 were down-reg-ulated.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGGs)analysis showed that:In chro-nic inflammatory pain model mice,DEGs of vlOFC were mainly manifested in biological processes such as organic cation transport,neurotransmitter transport,and regulation of cytoplasmic calcium ion concentration.It is related to G protein-coupled receptors(GPCRs),neuropeptides and ammonium transport.DEGs mainly focuses on neuroactive ligand-receptor interactions,cytokine-cytokine receptor interactions,and cAMP signaling pathways.Reactome functional en-richment analysis showed that the pathway with the highest number of DEGs enriched and the lowest P value-adjusted was GPCRs ligand binding.Conclusion:Ion transport,neurotransmitter transport and binding,and GPCRs-related ac-tivities in vlOFC are involved in the regulation of chronic inflammatory pain.

Objective: To assess whether carbon monoxide (CO) poisoning increases the incidence of dementia. Methods: We searched the Cochrane Library, PubMed, and EMBASE from inception to 14 August 2022. Two authors independently selected studies, assessed the quality of included studies, and extracted data. Any disagreement was resolved by discussion with a third author. Only cohort study with an enough follow-up period was included for systematic reviews and meta-analysis. Results: Thirty-three full texts were initially searched, but only three studies met our inclusion criteria, and they were comprised of 134,563 participants who were initially free of dementia. The follow-up period ranged from 9 to 12 years. We found that CO poisoning increased the risk of dementia incidence (adjusted hazard ratio 2.61, 95% confidence interval 1.56 to 4.36, p=0.0003). Subgroup analysis showed that the increased dementia risk was significant in males but not in females, and the highest risk was in young age group, followed by in middle age group, but not in the old one. Conclusion Overall the evidence from prospective cohort studies supported a link between CO exposure and an increased dementia risk, although all the included studies were limited to Taiwanese population.

ObjectiveFocused on the laboratory animal domestication and breeding of domestic cats, to explore the feeding management methods and breeding techniques of experimental cats. MethodsSeven Chinese garden cats from three litters were introduced from the rural suburbs of Guangzhou, and a breeding seed colony was established. The cats were domesticated in captivity, bred, closed breeding and transmission according to the feeding and management methods of laboratory animal. The population reproduction, the number of pregnancies per year, the litter season, the birth and weaning quality of the cats, and the survival rate of weaning were statistically collected. ResultsThe young breeding cats were able to adapt to the cage feeding management. In the transmission breeding and the expanded breeding colony, the number of female cats pregnant with one, two or three litters a year accounted for 63.2%, 26.3% and 10.5%, respectively. The proportions of litters born from the 1st to the 4th quarters were 20.7%, 20.7%, 27.6%, and 31.0%. A total of 29 pregnancies and 101 kittens were got from 19 female cats, with an average of (3.5±1.33) kittens per litter. The birth weights of female and male cats were (89.31±13.69) g and (93.47±15.12) g, respectively. Sixty-seven kittens survived from weaning. The average survival rate was 60.86%, and the weaning weights of female and male cats were (361.62±82.77) g and (376.0±91.71) g, respectively. ConclusionDomestic Chinese garden cats can adapt to laboratory animal feeding and breeding rules, and have strong fertility. They can normally pregnant and breeding throughout the year. The kittens grow to 5-6 months of age can meet the weight requirements for the examination of pharmaceutical hypotensive substances, and can be used as experimental cats for pharmaceutical examination with clear origin.

Objective:To investigate the risk factors for death in children with acute necrotizing encephalopathy (ANE) in pediatric intensive care unit (PICU).Methods:This was a multicenter retrospective study. Thirty-nine children with ANE were from PICUs in 4 centers from December 1, 2014 to December 1, 2020. The 4 participating centers were Beijing Children′s Hospital, Shengjing Hospital of China Medical University, Hebei Children′s Hospital, and Bao′an Maternity & Child Health Hospital. Patients were divided into survival and non-survival groups by the outcome at discharge, and the differences in clinical data between the two groups were compared. Risk factors for death in children with ANE and the odds ratios ( OR) were analyzed by univariable Logistic regression. Results:Thirty-nine children with ANE were included. There were 18 males and 21 females. The median onset age was 30 months. The mortality at discharge was 41% (16/39). The onset age of most patients (74%, 29/39) was younger than 4 years old. Influenza virus was the most common precursor infection (80%, 20/25). Patients with shock at PICU admission were more common in the non-survival group (12/16 vs. 17% (4/23), P=0.001). Glasgow coma score (GCS) at PICU admission was significantly lower in the non-survival group than survival group (3 (3, 6) vs. 6 (5, 7), Z=-2.598, P=0.009). The optimal cut-off value was 4. The proportion of patients with GCS ≤ 4 at PICU admission was higher in the non-survival group (10/16 vs. 22% (5/23), P=0.018). ANE severity score (ANE-SS) at PICU admission was significantly higher in the non-survival group (5 (2, 6) vs. 2 (1, 4), Z=-2.436, P=0.015). The proportion of patients with high risk ANE-SS was higher in non-survival group than the survival group (9/16 vs. 22% (5/23), P=0.043). The proportion of application of high-dose methylprednisolone (20 mg/(kg·d)) was significantly higher in survival group than non-survival group (43% (10/23) vs. 1/13, P=0.031). Univariable Logistic regression indicated that risk factors for death in children with ANE were shock ( OR=14.250, 95% CI 2.985-68.018, P=0.001), GCS≤4 ( OR=6.000, 95% CI 1.456-24.733, P=0.013) and high risk ANE-SS ( OR=4.629, 95% CI 1.142-18.752, P=0.032) at PICU admission. Conclusions:ANE usually occurs in children under 4 years old after influenza infection. Shock, GCS≤4 and high risk ANE-SS at PICU admission were risk factors for death in children with ANE. High-dose methylprednisolone may improve the prognosis of children with ANE.

Objective:To observe the efficacy and safety of olaparib combined with bevacizumab in patients with recurrent platinum-sensitive ovarian cancer, and the effect on serum levels of human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125) and circulating tumor cells (CTCs).Methods:A total of 96 patients with recurrent platinum-sensitive ovarian cancer admitted to Dongfeng Hospital Affiliated to Hubei Medical College from June 2018 to June 2019 were selected and divided into control group ( n=48) and study group ( n=48) according to the random number table method. The control group was given doxorubicin liposomes combined with carboplatin chemotherapy for 6 cycles, and the study group was given olaparib combined with bevacizumab, continuous olaparib, and bevacizumab for 6 cycles. The median progression-free survival (PFS), the objective effective rate (ORR), disease control rate (DCR) of the two groups were evaluated, the changes of serum HE4, CA125 and CTCs levels of the two groups after treatment were compared, and the adverse drug reactions of patients during treatment were observed. Results:The median PFS of the study group was 8.3 months, which was longer than 5.5 months of the control group, with a statistically significant difference ( χ2=5.134, P=0.025). The ORR and DCR of the study group were 52.08% (25/48) and 81.25% (39/48), which were significantly higher than 31.25% (15/48) and 62.50% (30/48) of the control group, with statistically significant differences ( χ2=4.286, P=0.038; χ2=4.174, P=0.041). After 6 cycles treatment, serum HE4 [(123.60±31.52) pmol/L vs. (178.01±46.22) pmol/L], CA125 [(33.52±10.61)U/L vs. (50.32±11.09) U/L] and CTCs [(2.19±0.24) pcs/5 ml vs. (3.25±0.31) pcs/5 ml] of the study group were significantly lower than those of the control group, with statistically significant differences ( t=8.489, P=0.025; t=7.562, P=0.032; t=9.341, P=0.017). The incidences of gastrointestinal reactions [35.42% (17/48) vs. 64.58% (31/48)], bone marrow suppression [18.75% (9/48) vs. 41.67% (20/48)], liver and kidney function damage [2.08% (1/48) vs. 14.58% (7/48)], cardiotoxicity [4.17% (2/48) vs. 18.75% (9/48)], allergy reaction [0 (0) vs. 8.33% (4/48)], neurotoxicity [2.08% (1/48) vs. 16.67% (8/48)] and other adverse reactions of the study group were significantly lower than those of the control group, with statistically significant differences ( χ2=8.167, P=0.004; χ2=7.584, P=0.006; χ2=4.909, P=0.027; χ2=5.031, P=0.025; χ2=4.174, P=0.041; χ2=6.008, P=0.014). Conclusion:For patients with recurrent platinum-sensitive ovarian cancer, olalapril combined with bevacizumab has better curative effect than doxorubicin liposome combined with carboplatin chemotherapy, and can prolong the survival period of patients, down-regulate serum HE4, CA125 and CTCs levels, with low incidence of adverse reactions.

Objective To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China.Methods A total of 3502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected,and based on the age and sex specific waist circumference (WC) standards in the BCAMS study,1196 central obese cases and 2306 controls were identified.Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method.A total of 6 single nucleotide polymorphisms (FTO rs9939609,MC4R rs17782313,BDNF rs6265,PCSK1 rs6235,SH2B1 rs4788102,and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems,Foster City,CA,USA).Logistic regression model was used to investigate the association between 6 SNPs and central obesity.Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method,and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR.Results After adjusting gender,age,Tanner stage,physical activity and family history of obesity,the FTO rs9939609-A,MC4Rrs 17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model (OR=1.24,95％CI:1.06-1.45,P=0.008;OR=1.26,95％CI:1.11-1.43,P=2.98 × 10-4;OR=1.18,95％ CI:1.06-1.32,P=0.003).GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 (P=0.001).The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539.This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated.Moreover,the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender,age,Tanner stage,physical activity and family history of obesity.Conclusions Our study showed that FTO rs9939609-A,MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity,and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

Objective: The present study aimed to prospectively validate whether the single nucleotide polymorphisms (SNPs) in obesity-related genes were associated with change in body mass index (BMI) and obesity status during childhood. Methods: Based on the Beijing Child and Adolescent Metabolic Syndrome study (BCAMS), which was initiated between April and October in 2004, we conducted a follow-up study among 1 624 children aged 6 to 11 years old with genetic data in December 2010. A total of 777 children (246 obese and 531 non-obese) were reassessed for BMI. Z-score of BMI was used to standardize for age and sex. The changes in BMI Z-score during follow up were calcnlated SNPs were genotyped by quantitative Real-time PCR (rs9939609, rs6499640, rs7138803, rs1805081, rs17782313, rs6265, rs10938397, rs6235, rs29941, rs2844479, rs10913469 and rs4788102). Overweight and obesity were diagnosed by the age-and sex-specific BMI cutoffs recommended by the International Obesity Task Force. A multilocus genetic risk score for BMI was calculated as the simple sum of alleles of all the SNPs associated with BMI. Linear regression models and logistic regression models were performed to assess the associations of change in BMI Z-score and obese status with genotypes (assuming an additive model), respectively. Results: During 6 years of follow-up, 158 previously obese children remained obese as they aged into adolescence, and 88 transiently obese children were not obese during the second survey, 58 children were newly identified obese, and the other 473 children remained their non-obese state. BMI Z-score increased from 1.41±0.05 at baseline to 1.57±0.06 at follow up.The genotypes of the SNPs except rs6499640(P=0.033) and rs6265(P=0.041) were in Hardy-Weinberg equilibrium in each group (P>0.05). Each additional copy of the rs9939609 A allele was significantly associated with an increase in BMI Z-score (β=0.205, P=0.014) during follow up. Per C allele of rs17782313 was associated with an increase in BMI Z-score at baseline (β=0.268, P=0.003). As the non-obese reference, a significantly relative risk of obesity at follow up was observed for children carrying rs9939609 A-allele versus the T-allele carriers (OR=2.37, 95%CI: 1.45-3.88, P=0.001). Rs17782313 C-allele was significantly increase the risk of obesity only at baseline (OR=1.79, 95%CI: 1.24-2.60, P=0.002). Rs1805081 A-allele was significantly associated with durative of obesity (OR=1.45, 95%CI: 1.04-2.03, P=0.028). Each unit higher genetic risk score was associated with increases risk of 0.18 times (OR=1.18, 95%CI: 1.05-1.33) in childhood transient obesity, and 0.22 times (OR=1.22, 95% CI: 1.06-1.42) in incident obesity at follow-up. But it was not significantly associated with persisted obesity during 6 years of follow-up (OR=1.09, 95% CI: 0.99-1.20). Conclusion We confirmed that the change of BMI and obesity status in children was affected by different genetic factors. Individual who carries more risk alleles in obesity-related genes may increase the susceptibility to obesity.

Objective To systematically evaluate the associations between SEC16B polymorphisms and body mass index (BMI) or risk of obesity in different ethnic populations.Methods A literature retrieval was carried out by using Wanfangdata,Chinese National Knowledge Infrastructure (CNKI),China Science and Technology Journal Database (VIP databases),PubMed,Embase,Web of Science,NIH GWAS catalog databases to collect the research papers published between 2009 and 2015 on the associations between SEC16B polymorphisms and BMI or risk of obesity.Summary beta estimates (βs),odds ratios (ORs) and 95％ confidence intervals (CIs) were calculated to assess the strength for the BMI analyses and obesity status.Meta-analysis was performed with Stata 12.0 software.Results Totally 15 papers for rs10913469 and 13 papers for rs543874 were included in this Meta-analysis.Under additive genetic model,rs10913469 and rs543874 in SEC16B gene were positively associated with BMI,and the combined β was 0.04 (95％CI:0.03-0.05) and 0.03 (95％CI:0.02-0.04),respectively,and rs10913469 and rs543874 were also associated with the risk of obesity,and the combined OR was 1.11 (95％CI:1.08-1.15) and 1.28 (95％CI:1.20-1.36),respectively.There were no significant differences among subgroups of ethnicity,different age groups and literatures with different quality.Conclusion rs10913469 and rs543874 in SEC16B gene are significantly associated with BMI and the risk of obesity,and C allele ofrs10913469 and G allele ofrs543874 increase the risk for obesity in different ethnic populations.