G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Objective To investigate the effect of endoscopic posterior rhinoplasty in the treatment of post-radiotherapy atretorrhinia in the patients with nasopharyngeal carcinoma,and to analyze the postopera-tive recurrence influencing factors.Methods The clinical data in 60 patients with post-radiotherapy nasal atre-torrhinia due to nasopharyngeal carcinoma diagnosed and treated in this hospital from January 2019 to January 2023 were analyzed retrospectively.They were treated by endoscopic posterior rhinoplasty.The operation situ-ation and postoperative related complications occurrence were recorded.The visual arialogue scale (VAS) was used to evaluate the severity degrees of subjective symptoms before operation and on postoperative 1,3 months.The recurrence situation conducted the statistics.The univariate and multivariate logistic regression was used to analyze the influencing factors of postoperative recurrence.Results The surgical time in 60 cases was (65.12±5.23)min,and intraoperative blood loss volume was (25.02±1.46)mL.Eight cases developed recurrence after surgery.The VAS scores of subjective symptoms such as nasal congestion,rhinorrhea,mouth dryness and olfactory dysfunction on postoperative 1,3 months were decreased compared with before opera-tion (P<0.05).The multivariate logistic regression analysis revealed that postoperative nostril size,exposure of normal mucosa,use of mucoperiosteal flap and regular postoperative regular nasal endoscopic re-examina-tions were the independent influencing factors of postoperative recurrence in the patients with post-radiothera-py atretorrhinia after endoscopic posterior rhinoplasty treating nasopharyngeal carcinoma (P<0.05).Conclu-sion Using endoscopic posterior rhinoplasty for treating atretorrhinia after nasopharyngeal carcinoma radio-therapy has good effect,which could improve the subjective symptoms of the patients.The nostril size,normal mucosa exposure and regular re-examinations may affect the postoperative recurrence.

Objective To analyze the distribution and antimicrobial resistance of pathogens from wounds of burned patients,providing reference for the rational use of antimicrobial agents and healthcare-associated infection(HAI)prevention and control.Methods Clinical data of burned patients admitted to a tertiary first-class hospital from Ja-nuary 2020 to December 2022 were analyzed retrospectively,pathogens in the wound was cultured,identified,and performed antimicrobial susceptibility analysis.Results From 2020 to 2022,a total of 588 burned patients were ad-mitted,734 strains of pathogens were detected,including 415 strains(56.54％)of Gram-negative bacteria,306 strains(41.69％)of Gram-positive bacteria,and 13(1.77％)strains of fungi.The top 5 pathogens were Staphy-lococcus aureus,Escherichia coli,Pseudomonas aeruginosa,Klebsiella pneumoniae,and Enterobacter cloacae.Staphylococcus aureus had higher resistance rates(93.02％-97.37％)to penicillin G,resistance rate to oxacillin increased from 11.63％to 21.92％.Pseudomonas aeruginosa mainly exhibited resistance to ticarcillin/clavulanic acid,aztreonam,and levofloxacin,resistance rates to imipenem and meropenem were 15.00％-38.10％and 10.00％-33.33％,respectively.Susceptibility of Enterobacterales bacteria to cephalosporins enhanced with the increased of cephalosporin generations,and exhibited higher resistance to commonly used antimicrobial agents.Conclusion Over the past three years,there has been no significant change in the detection of major pathogens and antimicrobial resistance in wounds of burned patients in this hospital.Antimicrobial resistance of Staphylococcus aureus and En-terobacterales is relatively severe,and it is necessary to carry out surveillance on pathogens from burn wounds in corresponding areas.

Objective: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). Materials and Methods: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. Results: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87–13.40]), IVHG (3.64 [2.15–6.24]), and RHE (7.90 [4.93–12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52–0.66]), IVHG (0.72 [0.64–0.81]), and RHE (0.61 [0.54– 0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36–15.30] and 10.10 [7.10–14.60], respectively, for the blend sign and 2.75 [1.64–4.67] and 2.62 [1.60–4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. Conclusion Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.

Objective:To analyze the non-enterovirus A71 (non-EVA71) and non-coxsackievirus A16 (non-CVA16) enteroviruses causing hand, foot and mouth disease (HFMD) in Kunming and Qujing of Yunnan Province in 2021 by sequencing the VP4/VP2 and VP1 genes and to analyze the phylogenetic characteristics of the VP1 gene of CVA2, aiming to provide reference for the prevention and control of CVA2.Methods:The samples were made and extracted strictly according to the Laboratory Manual for Hand, Foot and Mouth Disease (China Center for Disease Control and Prevention, 2018 Edition). VP4/VP2 junction regions were firstly amplified and sequenced by MD91/OL68-1 primers. These sequences were firstly edited and then "blasted" on the GenBank to determine the virus serotype. To analyze the phylogenetic characteristics of CVA2, the entire VP1 gene sequences were amplified in two segments using enterovirus species A primers. Virus serotype was again confirmed online by "Enterovirus Genotyping Tool Version 0.1". The sequences of the reference virus genotypes/sub-genotypes were downloaded according to the reference. The phylogenetic trees were constructed by Mega5.2 software and the genetic characteristics were analyzed.Results:A total of 749 non-EVA71 and non-CVA16 enteroviruses were detected in the two areas in 2021. Group A enteroviruses were the main pathogens, with CVA16 as the predominant virus, and a small number of group B enteroviruses were reported. Only five strains of CVA2 were detected with a detection rate of 0.67% (5/749), indicating that CVA2 was a rare pathogen for HFMD in the two areas. The sequencing and serotyping results were consistent using the two genomic regions of VP4/VP2 junction region and VP1 region. Phylogenetic analysis showed that three Kunming strains belonged to genotype A, while two Qujing strains belonged to genotype D.Conclusions:The detection rate of CVA2 in Kunming and Qujing was 0.67% in 2021. CVA2 was a rare pathogen for HFMD in the two regions. Phylogenetic analysis showed genotypes A and D spread in Kunming and Qujing, respectively, but had not caused epidemics. To our knowledge, this was the first report of genotype A of CVA2 in China. Strengthening the laboratory surveillance especially molecular epidemiological surveillance is valuable for the monitor and analysis of transmission source for CVA2.

Objective:To study the genetic characteristics and genetic evolution of echovirus 30 (ECHO30) isolates in Yunnan Province, China.Methods:Virus isolation was performed on nucleic acid-positive samples for hand, foot, and mouth disease pathogen surveillance in Yunnan Province, and VP1 gene sequencing was performed. The sequences of eight ECHO30 isolates from Yunnan Province and the gene sequences of the VP1 region of the ECHO30 reference strain downloaded from GenBank were compared and analyzed using MEGA 5.0 software, and then a phylogenetic tree was constructed to measure the homology of nucleotides and amino acids between the isolates.Results:The ECHO30 virus was distributed in Wenshan, Qujing, Chuxiong, and Kunming in Yunnan Province. The ECHO30 virus was relatively common in Wenshan. ECHO30 isolates belonged to the H2 subtype of the H genotype, which was close to the local reference strain LC120939 in Yunnan Province. On the VP1 gene at site 5, the amino acid change ratio was more active, the amino acids were diverse, and mutations also occurred at sites 54, 156, 258, and so on. Nucleotide and amino acid homology were 84.0% - 100.0% and 98.4% - 100.0%, respectively.Conclusions:ECHO30 isolates from Yunnan Province have certain geographical characteristics and belong to H2 of the H genotype. The nucleotide differences in virus sequences among subtypes are small and have a close genetic relationship.

Abstract: Objective　To analyze the results of the surveillance of hand, foot and mouth disease (HFMD) pathogens in Baoshan City, Yunnan Province in 2022, and to analyze the genetic characteristics of the main epidemic strain coxsackievirus A16 (CVA16), in order to provide scientific basis for the prevention and control of HFMD. Methods　Samples of hand, foot and mouth disease cases in Baoshan City submitted to Yunnan Province in 2022 were selected, the samples were processed, and the viral nucleic acid was extracted, and the Enterovirus (EV) VP4/VP2 binding region gene was amplified with primers (MD91/OL68-1) and sequenced. The sequence was BLAST searched in GenBank to determine the virus type, and then the full sequence of VP1 region was amplified with relevant primers of each type of virus and sequenced. Viruses were identified by using Enterovirus Genotyping Tool Version 1.0. according to the reference documents, the reference sequences were downloaded for making the phylogenetic tree, and the test results were statistically analyzed. Results　A total of 307 clinical samples of hand-foot-mouth disease in Baoshan City in 2022 were detected by real-time RT-PCR. There were 280 laboratory-confirmed cases (91.21%), among which the detection rate of CVA16 was 55.05% (169/307), EV-A71 was 3.58% (11/307), and other enteroviruses were 32.57% (100/307). Of the 206 HFMD test specimens, the VP4/VP2 junction and VP1 gene sequences of enterovirus were amplified and identified, and 29 enterovirus strains were obtained, with a positive virus rate of 14.08% (29/206). All viruses belonged to group A and were divided into 3 serotypes, which included 27 strains of CVA16 (93.10%, 27/29), 1 strain of EV-A71 (3.45%, 1/29), and 1 strain of CVA10 (3.45%, 1/29). Group B, C, and D viruses were not detected. The positive rate of VP4/VP2 binding region and VP1 region of coxsackievirus A16 gene in Baoshan City in 2022 was 13.11% (27/206). The genetic evolution analysis showed that the 27 strains of CVA16 belong to B1a subtype and can be divided into two evolutionary branches. Conclusions　In 2022, the main epidemic strain of HFMD in Baoshan City, Yunnan Province is CVA16 gene, belonging to B1a subtype, which can be divided into two branches, indicating 2 transmission chains prevalent in Baoshan City. Future efforts should focus on strengthening surveillance, improving the quality of monitoring, and understanding the characteristics of viral prevalence..

Objective:To analyze the etiological characteristics of hand, foot and mouth disease (HFMD) cases and to investigate the genetic characteristics of VP1 region of coxsackievirus A6 (CVA6) and CVA16 strains in Wenshan prefecture of Yunnan Province in 2020.Methods:Virus RNA was extracted directly from stool samples of children with HFMD in Wenshan prefecture of Yunnan Province in 2020. Enterovirus (EV) VP4/VP2 junction region was amplified using MD91/OL68-1 primers and sequenced, and then the serotypes of EV isolates were preliminarily identified. Amplification and sequencing of the complete VP1 gene were performed. A phylogenetic tree was constructed by MEGA 5.2 software with the reference strains from GenBank. Genetic and molecular epidemiological characteristics of CVA6 and CVA16 were analyzed.Results:Thirty-two strains of EV and one strain of astrovirus MLB1 were detected in 317 specimens with an overall virus detection rate of 10.41% (33/317). Among the 32 EV strains, 31 (96.88%) were enterovirus species A (EVA) and one (3.12%) was EVB. EVC and EVD were not detected. CVA6 was the predominant EV, accounting for 62.50% (20/32), followed by CVA16 (18.75%, 6/32), CVA4 (9.37%, 3/32) and CVA10 (3.12%, 1/32). EVA71 was not detected. The phylogenetic analysis showed 20 CVA6 strains belonged to D3a sub-genotype and could be further divided into three clusters. Six CVA16 strains belonged to B1a sub-genotype, which was one of the predominant genotypes circulating in China, and could be divided into two clusters.Conclusions:The detection rate of pathogens causing HFMD in Wenshan prefecture in 2020 was 10.41% and the most common etiologic agents were CVA6 and CVA16. Based on the genetic analysis of the VP1 gene, the predominant genotype circulating in Wenshan prefecture in 2020 was CVA6 D3a sub-genotype, followed by CVA16 B1a sub-genotype. EVA71 was not detected.