OBJECTIVE To evaluate the cost-effectiveness of iruplinalkib for ALK-positive non-small cell lung cancer （NSCLC） patients who had not previously received ALK-tyrosine kinase inhibitors （TKIs） from the perspective of the Chinese healthcare system. METHODS Based on the INSPIRE clinical trial， a three-health state partitioned survival model was developed to simulate the progression of disease， with model cycle of 3 weeks and a life-year time range of 15 years； the discount rate was 5%. For the treatment of ALK-positive advanced NSCLC， total cost， quality-adjusted life year （QALY）， and incremental cost- effectiveness ratio （ICER） were compared between iruplinalkib and crizotinib； using 1-3 times China’s per capita gross domestic product （GDP） （89 358-268 074 yuan） in 2023 as the willingness-to-pay （WTP） threshold， the cost-effectiveness of two regimens were compared. The sensitivity analysis and scenario analysis （altering the distribution of survival curves， utility values） were conducted to assess model robustness. RESULTS Compared with the crizotinib regimen， the ICER for the iruplinalkib regimen was 194 412.74 yuan/QALY， which was below the WTP threshold of three times China’s per capita GDP in 2023 yuan）. The results under the scenario of altering the survival curve distribution were consistent with the base case analysis. However， after increasing the utility value of the disease progression state， the ICER exceeded the WTP threshold， and iruplinalkib no longer had a cost-effective advantage. The results of the one-way sensitivity analysis indicated that the cost of iruplinalkib and the utility values of disease progression states had a significant impact on the ICER. The probabilistic sensitivity analysis confirmed the robustness of the base case analysis results. CONCLUSIONS From the perspective of China’s healthcare system， compared with crizotinib regimen， the therapy with iruplinalkib is cost-effective for ALK-positive NSCLC patients who have not previously received ALK-TKIs.

To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up.

To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE).

On August 24 2024, Xiaoshan District Center for Disease Control and Prevention, Hangzhou City, received a report of two cases of varicella infection among staff in the intensive care unit (ICU) of a hospital in its jurisdiction. The center immediately organized personnel to conduct an epidemiological investigation of the cases and their close contacts. The index case was a patient admitted to the ICU who had large areas of red rash and pustules on the chest, back, and right axilla. This case was diagnosed with herpes zoster by a dermatology consultation within the hospital. The other nine secondary cases were all nursing staff in the ICU, who were clinically diagnosed with varicella between August 21 and September 1, with an attack rate of 14.06%. All secondary varicella cases had a history of contact with the herpes zoster case and no history of varicella infection. Their varicella vaccination history was unknown. Based on the results of the on-site epidemiological and sanitary investigations, it was determined that this was an outbreak of varicella in the hospital caused by a herpes zoster case. After the last case was diagnosed, no new cases were reported within the longest incubation period (21 days), and the outbreak was declared over on September 21. Close contact with the herpes zoster case was likely the main cause of the outbreak. This highlights the need for early identification and isolation of suspected herpes zoster cases in hospitals in the future, as well as enhanced protective measures to prevent nosocomial infections.

Objective To analyze the causal relationship between statins and type 1 or type 2 diabetes mellitus by using Mendelian randomization(MR).Methods Based on the collected data of genome-wide association studies(GWAS),single nucleotide polymorphism(SNP),which were independent of each other and highly correlated with statins and diabetes mellitus,were selected as tool variables.MR-Egger regression,weighted median,inverse variance weighting(IVW),simple mode and weighted mode were used for two-sample MR analyses to evaluate the causal relationship between statins and type 1 or type 2 diabetes respectively,and heterogeneity tests,multiplicity analyses,and sensitivity analysis to evaluate the reliability of the study.Results A total of 78 SNPs independently associated with statins were included as tool variables in this study at the genome-wide significance level(P＜5×10-8).The results of IVW analysis showed that statins were causally associated with an increased risk of type 1 diabetes mellitus(OR=1.524,95％CI 1.077 to 2.157,P=0.017),and there was also a causal relationship between statins and the increased risk of type 2 diabetes(OR=1.261,95％CI 1.165 to 1.366,P＜0.001).The results were not affected by multiplicity and heterogeneity,and the reliability of the results was verified by sensitivity analysis.Conclusion Statins may be a risk factor for increasing the risk of type 1 or type 2 diabetes.However,further studies with larger sample sizes of GWAS data are still needed to verify the causal association.

Objective:To explore regulatory effects of short-chain fatty acids (SCFA) on hypoxia-induced oxidative stress and activation of pancreatic stellate cells (PSCs) .Methods:PSCs were cultured in normoxia or hypoxia conditions to establish normoxia or hypoxia group. PSCs were pre-treated with SCFA working solution (10 mmol/L sodium acetate, 0.5 mmol/L sodium propionate and 0.5 mmol/L sodium butyrate), and then cultured in hypoxia conditions to establish the hypoxia-SCFA group. PSCs pre-treated by normal saline was set as the hypoxia-control group. The relative growth viability of the cells was detected by the CCK-8 assay. Relative levels of reactive oxygen species (ROS) were detected by DCFH-DA fluorescence probe method. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. Protein expression of cyclin-associated marker cyclin A and cyclin D, hypoxic marker HIF1α, activation marker α-SMA, and antioxidant marker NRF2 and HO-1 was detected by western blotting.Results:The relative viability of PSCs in hypoxia group was significantly higher than that in normoxia group at 48 h (1.23±0.05 vs 0.99±0.04), but the relative viability of hypoxia-SCFA group was significantly lower than that of the hypoxic-control group at both 36 h and 48 h (0.69±0.01 vs 0.86±0.03, 0.86±0.02 vs 1.25±0.05). The relative level of ROS was significantly higher in hypoxia group than normoxia group (1.74±0.11 vs 1.00±0.10). The relative level of ROS was significantly lower in the hypoxia-SCFA group than the hypoxia-control group (1.39±0.14 vs 1.66±0.11). The fluorescence signals of JC-1 polymer in hypoxia group were significantly higher than those in normoxia group (1.36±0.05 vs 1.00±0.11), whereas the fluorescence signals of JC-1 polymer were significantly lower in hypoxia-SCFA group than in hypoxia-control group (1.11±0.03 vs 1.32±0.06). The expression of cyclin A, cyclin D, HIF1α, α-SMA, NRF2, and HO-1 was significantly higher in hypoxia group than those in normoxia group (1.19±0.01 vs 0.63±0.02, 0.93±0.02 vs 0.83±0.03, 1.18±0.07 vs 0.41±0.02, 1.19±0.14 vs 0.66±0.04, 1.22±0.11 vs 0.61±0.04, 1.28±0.12 vs 0.68±0.02), but the expression of cyclin A, cyclin D, α-SMA, NRF2, and HO-1 in Hypoxia-SCFA group was significantly lower than those in hypoxia-control group (0.79±0.04 vs 1.15±0.03, 0.88±0.01 vs 0.95±0.03, 0.87±0.01 vs 1.18±0.05, 0.84±0.01 vs 1.22±0.04, and 0.92±0.02 vs 1.27±0.06). All these differences were statistically significant (all P values <0.05) . Conclusions:SCFA significantly improves the oxidative stress state of PSCs under hypoxic conditions, maintains the stability of mitochondrial membrane potential, and inhibites hypoxia-induced activation of PSCs.

Objective:To analyze the changes and clinical significance of homocysteine (Hcy), folate, and cardiac enzyme levels in patients with alcohol dependence and depression.Methods:A total of 102 patients with alcohol dependence and depression, who received treatment at Wenzhou Seventh People's Hospital from January 2022 to June 2023, were included in the observation group. The degree of alcohol dependence in patients in the observation group was assessed using the Michigan Alcoholism Screening Test (MAST). According to the assessment results, the patients in the observation group were divided into the following subgroups: mild alcohol dependence ( n = 33), moderate alcohol dependence ( n = 37), heavy alcohol dependence ( n = 15), and severe alcohol dependence ( n = 17). The severity of depression among patients in the observation group was assessed with the Hamilton Depression Scale (HAMD). Based on the assessment results, the patients in the observation group were divided into the following subgroups: mild depression ( n = 43), moderate depression ( n = 34), and severe depression ( n = 25). The cognitive function of patients in the observation group was assessed using the Montreal Cognitive Assessment Scale (MoCA). According to the assessment results, the patients in the observation group were divided into normal cognitive function ( n = 73) and cognitive impairment ( n = 29) subgroups. Thirty healthy volunteers from our hospital during the same period were included in the control group. The levels of Hcy, folate, and cardiac enzymes were compared among all groups. The correlations between Hcy, folate, and cardiac enzyme levels with HAMD, MoCA, and MAST scores were analyzed using the Pearson method. Results:The Hcy level in the observation group was (15.21 ± 1.99) μg/L, which was significantly higher than that in the control group [(11.38 ± 1.46) μg/L, t = -9.80, P < 0.001]. The levels of folate, lactate dehydrogenase (LDH), and creatine kinase (CK) in the observation group were (4.82 ± 1.77) μg/L, (122.69 ± 33.98) IU/L, and (87.83 ± 16.52) IU/L, respectively, which were significantly lower than those in the control group [(6.27 ± 1.35) μg/L, (150.56 ± 38.78) IU/L, (98.67 ± 20.29) IU/L, t = 4.16, 3.82, 2.99, all P < 0.05]. The Hcy levels in the mild , moderate, heavy, and severe alcohol dependence subgroups [(13.16 ± 1.23) μg/L, (15.35 ± 0.82) μg/L, (16.79 ± 1.38) μg/L, (17.63 ± 1.22) μg/L] increased sequentially, while the folate levels [(6.11 ± 1.51) μg/L, (4.95 ± 1.40) μg/L, (4.04 ± 0.99) μg/L, (2.70 ± 0.99) μg/L], LDH levels [(153.35 ± 27.47) IU/L, (123.29 ± 16.59) IU/L, (109.83 ± 14.41) IU/L, (73.24 ± 16.86) IU/L], and CK levels [(104.14 ± 12.78) IU/L, (86.48 ± 9.15) IU/L, (78.11 ± 7.85) IU/L, (67.71 ± 9.00) IU/L] decreased sequentially. These differences in Hcy, folate, LDH, and CK levels among the mild, moderate, heavy, and severe alcohol dependence subgroups were statistically significant ( F = 73.24, 26.53, 59.08, 53.86, all P < 0.001). The Hcy levels in the mild, moderate, and severe depression subgroups [(13.75 ± 1.54) μg/L, (15.46 ± 1.17) μg/L, (17.39 ± 1.31) μg/L] increased progressively, while the folate levels [(5.83 ± 1.77) μg/L, (4.67 ± 1.12) μg/L, (3.28 ± 1.26) μg/L], LDH levels [(138.09 ± 33.67) IU/L, (119.73 ± 26.39) IU/L, (100.24 ± 30.88) IU/L], and CK levels [(96.35 ± 15.24) IU/L, (86.73 ± 15.62) IU/L, (74.69 ± 9.71) IU/L] decreased progressively. The differenes in Hcy, folate , LDH, and CK levels among the four depression subgroups were statistically significant ( F = 56.57, 24.36, 12.23, 18.44, all P < 0.001). The Hcy levels in the cognitive impairment group [(17.01 ± 1.63) μg/L] was significantly higher than that in the normal cognitive function group [(14.50 ± 1.64) μg/L, t = -6.97, P < 0.001), and the folate, LDH, and CK levels in the cognitive impairment group were (3.76 ± 1.78) μg/L, (102.71 ± 31.08) IU/L, and (76.00 ± 13.37) IU/L respectively, which were significantly lower than those in the normal cognitive function group [(5.24 ± 1.58) μg/L, (130.63 ± 31.92) IU/L, (92.52 ± 15.31) IU/L, t = 4.11, 4.01, 5.09, all P < 0.001]. Hcy levels were positively correlated with HAMD and MAST scores ( r = 0.854, 0.846, both P < 0.05) and negatively correlated with MoCA scores ( r = -0.648, P < 0.001). Folate, LDH, and CK levels were negatively correlated with HAMD and MAST scores ( r = -0.644, -0.701; r = -0.551, -0.696; r = -0.505, -0.673; all P < 0.001), and they were positively correlated with MoCA scores ( r = 0.514, 0.436, 0.448, all P < 0.001). Conclusion:In patients with alcohol dependence and depression, abnormal levels of Hcy, folate, and cardiac enzymes were observed. These indicators were found to be associated with the severity of alcohol dependence, the level of depression, and cognitive function.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

Objective:To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line.Methods:The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin.The levels of Pgp,p-AKT,and p-mTOR in cells were detected by Western blot.Cell viability was detected by MTT assay.IC50 was computed by SPSS.Results:The doxorubicin-resistant Burkitt lymphoma cell line,RAJI/DOX,was established successfully.The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line.NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line.NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line,and the effect was obvious when it was cooperated with doxorubicin.Conclusion:The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line.NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.