Objective To investigate the association of single nucleotide polymorphisms (SNPs) in COX-2 with aspirin resistance in Chinese cerebral infarction patients. Methods A total of 150 Chinese cerebral infarction patients were recruited. Platelet aggregation response was measured by light transmission aggregometry method and four SNPs located in COX2 gene were genotyped by sequencing method. Results Sixty patients of the total were classified as aspirin non-responders. For clinical variables , concentrations of high homocysteine and the frequency of recurrence cerebral infarction were significantly higher in aspirin non-responders when compared with aspirin responders. Univariate analysis of SNPs showed that rs20417 , rs689465 and rs689466 were significantly associated with aspirin resistance. Multivariate analysis indicated that after adjusting other SNPs and clinical risk factors, rs20417 and rs689466 were still significantly associated with aspirin resistance. Conclusions Rs689466 is significantly associated with aspirin resistance in Chinese cerebral infarction patients even after the adjustment of rs20417. By combining rs689466 , rs20417 and other clinical risk factors , we may better classify the aspirin non-responders from aspirin responders.

OBJECTIVE:To provide reference for promoting the rational use of essential drugs in primary medical institutions. METHODS:Twenty-three rural primary medical institutions(8 township health centers,15 village clinics)were randomly selected from 2 poverty-stricken counties in Chongzuo city of Guangxi Zhuang Autonomous Region. The utilization of essential drugs was investigated and analyzed statistically through exporting hospital information system data and on-site interviews. RESULTS:The utilization rate of essential drugs in sample township health centers was 72.4％,and the amount of essential drugs accounted for 78.3％. The utilization rate of variety from National List of Essential Drug was 36.9％,which in the Autonomous Regions Essential Drug List Supplement was 47.2％(utilization rate of chemical drugs was 53.9％,and that of Chinese patent drugs was 39.7％). The utilization rate of essential drugs in sample village clinics was 64.4％;utilization rate of variety from National List of Essential Drug was 18.3％, which in the Autonomous Regions Essential Drug List Supplement was 10.5％. The amount of 5 major categories accounted for 47.9％ of total amount of chemical agents,among which that of antimicrobial agents took up the highest proportion,being 35.9％. Among top 10 drugs in the list of amount,there were 8 national essential drugs and 4 antimicrobial agents. There were 2.90 kinds of drugs in each outpatient prescription averagely in sample township health centers;the average proportion of antibiotic prescription was 43.0％;the cost of each prescription was 33.12 yuan in average. CONCLUSIONS:The utilization rate of essential drugs in primary medical institutions is lower than the requirements of policy. There are great difference in utilization rate between chemical agents and Chinese patent drugs of township hospital in Autonomous Regions Essential Drug List Supplement. The cost proportion of antimicrobial agents is high. The rationality of prescription drug use still needs to be improved. It is suggested to guarantee essential drugs supply,adjust Autonomous Regions Essential Drug List Supplement in time,control the price of main categories and strengthen antimicrobial agent use monitoring so as to further promote rational drug use.

Objective: To study the effects of triptolide-medicated serum on secretory function of adrenocortical cells isolated from rats. Methods: Thirty SD rats were randomly divided into control group, prednisone group, and low-, medium- and high-dose triptolide groups. Rats were administered with normal saline, prednisone and low-, medium- and high-dose triptolide respectively by gastrogavage to prepare sera containing drugs. Primary adrenocortical cells were isolated from normal male rats and cultured with sera containing drug for 48 hours. Expression of proliferating cell nuclear antigen (PCNA) was observed by immunohistochemical method and number of PCNA-positive cells was counted. Ultrastructure of adrenocortical cells was observed under a transmission electron microscope. Content of corticosterone in supernatant of adrenocortical cell culture was detected by enzyme-linked immunosorbent assay, and real-time fluorescence quantitative polymerase chain reaction (PCR) was employed to investigate the expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNA. Results: As compared with the control group, content of corticosterone in supernatant of adrenocortical cell culture and expression of 3beta-HSD mRNA were significantly increased in the triptolide-treated groups, and the numbers of PCNA-positive cells were increased in the medium- and high-dose triptolide groups, however, they were decreased in the prednisone group. Conclusion: Triptolide-medicated serum can increase the secretion of corticosterone in rat adrenocortical cells in vitro.

Tertiary lymphoid structure (TLS) is the ectopic lymphoid tissue around the chronic inflammatory site of tumor, infection diseases, autoimmunity diseases, organ transplantation and so on. TLS is regarded as the vital niche of antitumor immune response in tumor microenvironment for abundant immune cells, and is correlated with better clinical outcomes and immunotherapy response in most solid tumors. As a typical inflammation-driven cancer, hepatocellular carcinoma (HCC) is controversial with the influence of TLS on patients prognosis. In this paper, the composition, formation mechanism, recognition and clinical value of TLS in HCC were briefly reviewed.

OBJECTIVE:To provide reference for promoting the rational use of essential medicines in primary medical institutions.METHODS:Twenty six rural primary medical institutions (13 township health centers,13 village clinics) were randomly selected from 2 poverty-stricken county (city) in Huanggang city of Hubei province.The utilization of essential medicine was investigated and analyzed statistically through exporting hospital information system data and on-site interviews.RESULTS:The utilization rate of essential medicine in sample township health centers was 76.9％,and the amount of essential medicine accounted for 93.0％;the utilization rate of essential medicine in sample village clinics was 89.7％.The utilization rate of variety from essential medicine list was 53.6％ in sample township health centers and 25.0％ in sample village clinics;the utilization rate of variety from National Essential Medicine List was higher than that of Provincial Essential Medicine List Supplement.The amount of 5 major categories as antimicrobial agents,cardiovascular agent in sample primary medical institutions accounted for 64.7％ of chemical agents.The top ten medicines in the list of amount were all essential medicine,9 of which were national essential medicines.There were 2.8 kinds of medicines in each outpatient prescription averagely in sample township health centers.The proportion of antibiotic prescription was 44.2％.CONCLUSIONS:The utilization rate of essential medicines in township health centers of this area is lower than WHO recommended value,and the ratio of amount meets the policy requirements.The utilization rate of variety from Provincial Essential Medicine List Supplement is in low level in primary medical institutions;the amount of anti-microbial drugs is in high level;the rationality of medicine use in prescriptions needs to be improved.It is suggested to adjust the type of provincial supplement list dynamically according to actual situation and control the price and amount of main categories strictly,the rationality of prescription.

Objective: To demonstrate the effects of symbiotic bacteria from lettuce on inactivation of norovirus（NV）. Methods: Symbiotic bacteria were isolated from the lettuces sampled from farmlands and supermarkets. NV mixed with symbiotic bacteria was set as the experimental group,without symbiotic bacteria as the control group. After the inactivation by high temperature,ultraviolet light（UV）and chlorine dioxide,the ratio of NV amount in the experimental group and the control group was calculated to evaluate the effects of symbiotic bacteria. The mechanism of symbiotic bacteria was revealed by detecting their effects on the protection of viral capsid protein from UV and on the adsorption of NV. Results: Eleven symbiotic bacteria were identified from lettuces,all of which were bacilli,mainly Pseudomonas. Ten symbiotic bacteria could improve the heat-resistant ability of NV,with Microbacterium oryzae,Cupriavidus taiwanensis（SC061204）,Pseudomonas furukawaii,Enterobacter tabaci and Pseudomonas resinovorans（SC061211）more significant. Eleven symbiotic bacteria could improve anti-UV ability of NV,with Pseudomonas putida,Microbacterium oryzae and Enterobacter tabaci more significant. Only one strain of Pseudomonas putida could improve anti-chlorine dioxide ability of NV（Class I hazard）. Pseudomonas putida,Microbacterium oryzae and Enterobacter tabaci could significantly reduce the damage of NV capsid protein. Nine symbiotic bacteria could promote NV adsorption into lettuces,with the promotion rates ranged from 1.04% to 46.73%;while Pseudomonas putida and Pseudomonas resinovorans（SC061211） could restrain NV absorption,with the promotion rates of -6.50% and -19.85%. Conclusion Symbiotic bacteria from lettuce may enhance the anti-inactivation of NV by protecting capsid protein and promoting adsorption of NV. It is recommended to control the presence of symbiotic bacteria in the process of inactivating NV.

Single cell RNA sequencing technique provides a strong technical support for the analysis of cell heterogeneity in biological tissues, and has been widely used in biomedical research. In recent years, considerable scRNA-seq data have been accumulated in the research of ocular fundus diseases. The ocular fundus is abundant for the network of vessel and neuron, which leads to the complicated pathogenesis of fundus diseases. Through single cell RNA sequencing technique, the expression of thousands of genes of certain cell types or even subtypes can be obtained in the disease environment. Single cell RNA sequencing technique accurately reveals the pathogenic cell types and pathogenic mechanisms of ocular fundus diseases such as neovascular retinopathy, which provides a theoretical basis for the birth of new diagnosis and treatment targets. The construction of multi-omics single-cell database of ocular fundus diseases will enable high-quality data to be further explored and provide an analysis platform for ophthalmic researchers.

Objective To investigate the effects of probiotics combined with sacubitril valsartan and amiodarone on short-term and long-term efficacy of patients with atrial fibrillation after radiofrequency ablation. Methods A total of 90 patients with atrial fibrillation after radiofrequency ablation in the First Hospital of Zhangjiakou City from June 2021 to June 2022 were selected and randomly divided into three groups, with 30 cases in each group. Control group was treated with amiodarone, sacubitril valsartan group was treated with amiodarone and sacubitril valsartan, and probiotics group was treated with probiotics, amiodarone and sacubitril valsartan. The recurrence situation, atrial structure indexes[left atrial diameter (LAD), left ventricular ejection fraction (LVEF), left ventricular end systolic volume index (LVESVI), left atrial volume (LAV), left ventricular end diastolic volume index (LVEDVI)], myocardial fibrosis indexes[galactin-3 (Gal-3), soluble growth stimulation expression gene 2 protein (sST2)], inflammatory response indexes[intercellular adhesion molecule-1 (ICAM-1), C reactive protein (CRP), interleukin-6 (IL-6)], neuroendocrine hormone indexes[aldosterone, norepinephrine (NE), angiotensin Ⅱ (AngⅡ)], metabolites of gut microbiota[total bile acids, trimethylamine oxide (TMAO)] and incidence of adverse events were compared among the three groups. Results At 12 months after treatment, the recurrence rate of the probiotics group was significantly lower than that of the sacubitril valsartan group and the control group (P < 0.05); after 3, 6 and 12 months of treatment, the LAD, LAV, LVESVI, LVEDVI, sST2 and Gal-3 in the probiotics group were significantly lower than those in the sacubitril valsartan group and the control group (P < 0.05), and these indexes in the sacubitril valsartan group were also significantly lower than those in the control group (P < 0.05); after 3, 6 and 12 months of treatment, the LVEF of the probiotics group was significantly higher than that of the sacubitril valsartan group and the control group (P < 0.05), and the LVEF of the sacubitril valsartan group was also significantly higher than that of the control group (P < 0.05); after 3, 6 and 12 months of treatment, the CRP, IL-6, ICAM-1, NE, aldosterone and AngⅡ in the probiotics group were significantly lower than those in the sacubitril valsartan group and the control group, and these indexes in the sacubitril valsartan group were also significantly lower than those in the control group (P < 0.05); after 3, 6 and 12 months of treatment, the TMAO and total bile acids in the probiotics group were significantly lower than those in the control group and the sacubitril valsartan group (P < 0.05); there was no significant difference in the incidence of adverse events among the three groups (P>0.05). Conclusion Probiotics combined with sacubitril valsartan and amiodarone can improve atrial structure after radiofrequency ablation of atrial fibrillation, inhibit myocardial fibrosis, reduce inflammatory response, regulate neuroendocrine hormones and metabolites of gut microbiota, prevent long-term recurrence of atrial fibrillation, and have a high safety.

OBJECTIVETo investigate Lanzhou area cases of hepatitis C virus (H-CV) infection with a 5'-non coding region (NCR) 2i genotype and core (C), envelope protein (E) and non-structural protein (NS5) 2a genotype and the relationship with therapeutic response to interferon-alpha (IFNa).

METHODSNine patients who received IFNa-based treatment for HCV between 2007 and 2009 at the Second People's Hospital of Gansu Province were selected for analysis.Restriction enzyme analysis was carried out for the 5'-NCR and sequencing was carried out for the other gene areas.The relationship between genetic variants and IFNaresponse was examined.

RESULTSOf the total nine HCV cases treated with IFNa-based therapies, five of the patients achieved sustained virological response (SVR), which included two cases with type 2 genotype and three cases with no MboI restriction enzyme point of tangency (i.e.type 1b). The remaining four patients that did not achieve SVR included one case of type 2a, with a 1b and 2a mixed state, and one case with 5'-NCR 2i genotype and C area, NS5 area 2a genotype; the other two cases had 5'-NCR and C area type 1b. Of the five cases with 5'-NCR 2i genotype, all had C 2a genotype and two had C/E 2a and NS5 2a genotypes.The seven patients that showed no response to ordinary IFNa were converted to long-term IFNa plus ribavirin combination antiviral treatment; five (71.4%) of the cases showed response in HCV RNA level and the patients treated with the pegylated form showed greater response.

CONCLUSIONHCV genotyping can only provide information on the particular region of gene sequence examined, and it is important to sequence all gene regions where mutations related to antiviral drug response are located. Peg-IFNa-2a combined with ribavirin may achieve better therapeutic effect in patients infected with 2i/2a recombinant forms of HCV.

Angiogenesis Inhibitors ; Antiviral Agents ; Drug Therapy, Combination ; Genetic Variation ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; Open Reading Frames ; Polyethylene Glycols ; Recombinant Proteins ; Recombination, Genetic ; Ribavirin ; Treatment Outcome

Objective:To explore the mechanism of gypenoside ⅩⅦ against cerebral ischemia/reperfusion (I/R) through nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrf2/ARE) signaling pathway.Methods:Forty SPF Sprague Dawley (SD) rats were randomly divided into sham operated group, I/R model group, 25, 50 and 100 mg/kg gypenoside ⅩⅦ groups ( n = 8). Gypenoside ⅩⅦ groups were administered 25, 50 or 100 mg/kg (0.01 mL/g) gypenoside ⅩⅦ by intragastric administration for 14 days; the other two groups received the same dose of saline. Rat cerebral I/R model was established by modified line bolt method; rats in the sham operated group underwent the same procedure without producing substantial embolization. After 24 hours of reperfusion, the neurological deficit scores of the rats in each group were assessed. Rat abdominal aortic whole blood was collected and the serum reactive oxygen species (ROS), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), superoxide dismutase (SOD), quinone NADH oxidoreductase 1 (NQO1), and malondialdehyde (MDA) were detected. Then whole brain tissue was harvested and penumbra tissue was isolated from cerebral cortex, the general condition of rat brain tissue and the volume of cerebral infarction were evaluated, the histopathological changes in the brain were observed under light microscopy, the mRNA expressions of Nrf2 and Keap1 were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR), the protein expressions of Nrf2 and Keap1 were determined by Western blotting. Results:After 24 hours of reperfusion, compared with the sham operated group, the score of neurological deficit and infarct volume were significantly increased, the NQO1, SOD and γ-GCS levels in serum were significantly decreased, MDA, HO-1 and ROS levels in serum were significantly increased, the Nrf2 and Keap1 mRNA and protein expressions in the ischemic penumbra were significantly increased in rats from I/R model group. Compared with the I/R model group, the neurological deficit scores (1.50±0.53, 1.37±0.52 vs. 2.75±0.46) and brain infarct volume [(19.8±5.1)%, (21.4±6.4)% vs. (42.3±5.8)%] were significantly reduced, serum NQO1, SOD, HO-1 and γ-GCS were significantly increased [NQO1 (ng/L): 186.05±10.38, 220.75±16.22 vs. 131.36±5.95, SOD (kU/L): 63.23±5.30, 72.70±8.62 vs. 36.75±6.55, HO-1 (ng/L): 60.57±7.93, 60.35±4.72 vs. 42.72±4.95, γ-GCS (kU/L): 8.81±0.53, 8.72±0.69 vs. 6.80±0.56], serum MDA and ROS levels were significantly reduced [MDA (μmol/L): 5.94±0.66, 5.61±0.53 vs. 10.88±1.34, ROS (kU/L): 69.11±4.23, 67.12±4.52 vs. 104.43±7.54], the mRNA and protein expressions of Nrf2 and Keap1 in the ischemic penumbra were significantly increased in rats from 50 mg/kg and 100 mg/kg gypenoside ⅩⅦ groups [Nrf2 mRNA (2 -△△Ct): 1.90±0.13, 2.13±0.18 vs. 1.48±0.11, Keap1 mRNA (2 -△△Ct): 1.78±0.11, 1.85±0.10 vs. 1.43±0.10, Nrf2/β-actin: 0.73±0.04, 0.79±0.03 vs. 0.60±0.03, Keap1/β-actin: 0.71±0.01, 0.76±0.03 vs. 0.61±0.01], all the comparative differences were statistically significant (all P < 0.01); 25 mg/kg gypenoside ⅩⅦ had no significant effect. Conclusion:Gypenoside ⅩⅦ (50 mg/kg and 100 mg/kg) may play a role in anti-cerebral I/R injury by regulating NQO1, SOD, HO-1, γ-GCS, ROS and MDA through Nrf2/ARE signaling pathway.