Glutathione peroxidase （GSH-Px） is a key selenoenzyme that protects the body from oxidative damage. A series of small molecular organic selenium compounds have been designed and synthesized as functional mimics of GPx, among which isoselenazolones are the most widely studied. Taking ebselen as a representative, the catalytic mechanism of isoselenazolones in mimicing GSH-Px activity in vivo, the therapeutic effects of isoselenazolones in stroke, sensorineurium deafness and tinnitus, treatmentresistant depression （TRD） and coronavirus disease 2019 （COVID-19）, and research on their chemical synthesis methods were summarized and discussed in this paper.

Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective:To analyze the epidemic characteristics and trends of visceral leishmaniasis (VL) in Shaanxi Province, and provide a basis for formulating control strategies.Methods:The information on VL cases in Shaanxi Province from January 2012 to December 2024 were obtained from the Shaanxi Provincial Infectious Disease Reporting Management System, and demographic data were collected from the Shaanxi Statistical Yearbook. Descriptive epidemiological method was used to analyze the prevalence and the distribution by the three dimensions (time, region, and population). Joinpoint 4.9.1.0 software and Geoda 1.6 software were used for regression analysis and spatial clustering analysis, respectively. SuperMap 8C software was used for visualization.Results:From January 2012 to December 2024, a total of 304 cases of VL were reported in Shaanxi Province, with an annual incidence rate of 0.06/100 000. VL cases occurred in all months of the year in Shaanxi Province with no significant seasonality, yet the onset was predominantly concentrated from April to August(52.30%, 159/304). The majority of cases were male (61.51%, 187/304), aged 5 months to 4 years (17.11%, 52/304), and farmers (67.11%, 204/304). A total of 54 districts (counties, cities) of 10 cities in the province had reported cases, mainly concentrated in Weinan City (49.34%, 150/304). Joinpoint regression analysis revealed a significant overall upward trend in the VL incidence rate in Shaanxi Province from 2012 to 2024 [average annual percent change (AAPC) = 12.60%, 95% confidence interval ( CI): 6.01% - 19.62%, t = 3.95, P < 0.001]. The year 2020 was identified as a turning point in the trend. The incidence rate showed a rapid upward trend from 2012 to 2020 [annual percent change (APC) = 23.75%, 95% CI: 13.33% - 35.12%, t = 5.62, P < 0.001]. Global spatial autocorrelation analysis indicated significant positive spatial autocorrelation in VL incidence in 2012, 2014, 2015, 2018, and 2022 (Moran's I > 0, Z > 1.96, P < 0.05). Local spatial autocorrelation analysis identified 12 "high-high" clustering areas from 2012 to 2024, mainly located in Shangluo City in southern Shaanxi Province, and Weinan City and Yan'an City in northern Shaanxi Province. Conclusions:From 2012 to 2024, VL cases in Shaanxi Province are predominantly male farmers. The incidence of VL shows an overall upward trend, with significant spatial clustering. The prevention and control situation is severe. It is imperative to strengthen control measures, including vector disinfection and health education, to effectively control the spread and transmission of VL.

Objective:To analyze the epidemic characteristics and trends of visceral leishmaniasis (VL) in Shaanxi Province, and provide a basis for formulating control strategies.Methods:The information on VL cases in Shaanxi Province from January 2012 to December 2024 were obtained from the Shaanxi Provincial Infectious Disease Reporting Management System, and demographic data were collected from the Shaanxi Statistical Yearbook. Descriptive epidemiological method was used to analyze the prevalence and the distribution by the three dimensions (time, region, and population). Joinpoint 4.9.1.0 software and Geoda 1.6 software were used for regression analysis and spatial clustering analysis, respectively. SuperMap 8C software was used for visualization.Results:From January 2012 to December 2024, a total of 304 cases of VL were reported in Shaanxi Province, with an annual incidence rate of 0.06/100 000. VL cases occurred in all months of the year in Shaanxi Province with no significant seasonality, yet the onset was predominantly concentrated from April to August(52.30%, 159/304). The majority of cases were male (61.51%, 187/304), aged 5 months to 4 years (17.11%, 52/304), and farmers (67.11%, 204/304). A total of 54 districts (counties, cities) of 10 cities in the province had reported cases, mainly concentrated in Weinan City (49.34%, 150/304). Joinpoint regression analysis revealed a significant overall upward trend in the VL incidence rate in Shaanxi Province from 2012 to 2024 [average annual percent change (AAPC) = 12.60%, 95% confidence interval ( CI): 6.01% - 19.62%, t = 3.95, P < 0.001]. The year 2020 was identified as a turning point in the trend. The incidence rate showed a rapid upward trend from 2012 to 2020 [annual percent change (APC) = 23.75%, 95% CI: 13.33% - 35.12%, t = 5.62, P < 0.001]. Global spatial autocorrelation analysis indicated significant positive spatial autocorrelation in VL incidence in 2012, 2014, 2015, 2018, and 2022 (Moran's I > 0, Z > 1.96, P < 0.05). Local spatial autocorrelation analysis identified 12 "high-high" clustering areas from 2012 to 2024, mainly located in Shangluo City in southern Shaanxi Province, and Weinan City and Yan'an City in northern Shaanxi Province. Conclusions:From 2012 to 2024, VL cases in Shaanxi Province are predominantly male farmers. The incidence of VL shows an overall upward trend, with significant spatial clustering. The prevention and control situation is severe. It is imperative to strengthen control measures, including vector disinfection and health education, to effectively control the spread and transmission of VL.

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.

Background Tuberculosis is the most common complication of pneumoconiosis, which accelerates the progression of pneumoconiosis. Pneumoconiosis combined with tuberculosis is a major health risk. Objective To understand the outpatient health service utilization for patients of pneumoconiosis combined with tuberculosis and its main influencing factors. Methods A stratified random sampling combined with non-random sampling was used to select 11181 pneumoconiosis patients in 27 provincial administrative regions (excluding Shanghai, Tianjin, Hainan, Tibet Autonomous Region, Taiwan, Hongkong and Macao Special Administrative Regions) from December 2017 to June 2021. A self-constructed questionnaire, i.e. Health Seeking Behaviors of Pneumoconiosis Patients and Their Influencing Factors, was used, which included basic information, outpatient and inpatient service utilization, and influencing factors of medical treatment behaviors of pneumoconiosis patients. The effective recovery rate of the questionnaire was 90.7%. All patients of pneumoconiosis combined with tuberculosis (n=762) were included as the study subjects. The difference of outpatient utilization in the past two weeks, choosing medical institutions, and the reasons of not seeking medical treatment between urban and rural areas, and the influencing factors of outpatient service utilization were analyzed. Results The study subjects were mainly silicosis combined with tuberculosis (502 cases, 65.9%) and coal workers' pneumoconiosis combined with tuberculosis (232 cases, 30.5%), aged (58.6±12.5) years old. The main region was Western China (45.1%), followed by Eastern China (22.1%), Centeral China (20.2%), and Northeastern China (12.6%). The outpatient utilization rate in the past two weeks was 38.5% (293/762), and the main medical institutions consulted were municipal or provincial hospitals (32.0%), district or county hospitals (28.6%), and township hospitals or health service centers (17.5%). Short distance (20.7%), the availability of specialist outpatient services (16.7%), high level of medical care (14.8%), and low medical cost (12.3%) were the main reasons in choosing medical institutions. Higher proportion of patients seeking medical services due to acute exacerbation in rural areas was reported than in urban areas in the past two weeks (P<0.01). In addition to being hospitalized (113 cases, 41.4%) and self-purchasing medicine (46 cases, 16.8%), the reasons for not seeking medical treatment were self-perceived mild symptoms (15.0%) and high medical cost without reimbursement (9.5%). The multiple regression results showed that outpatient rate for patients of pneumoconiosis combined with tuberculosis in the western region was higher than that in the eastern region (OR=1.66, 95%CI: 1.03, 2.68); patients with an annual personal income of 10000-35500 yuan had a higher outpatient rate than the > 35500 yuan income group (OR=2.54, 95%CI: 1.49, 4.36); the outpatient rate of silicosis patients was higher than that of coal workers' pneumoconiosis (OR=1.83, 95%CI: 1.23, 2.72); the outpatient rate of patients with clinically diagnosed cases (no classified stage of pneumoconiosis) was higher than that of patients with stage I pneumoconiosis (OR=2.32, 95%CI: 1.24, 4.31). Exacerbation of pneumoconiosis-related symptoms in past two weeks (OR=4.26, 95%CI: 2.89, 6.28), occupational injury insurance (OR=0.49, 95%CI: 0.30, 0.80), and hospitalization in past one year (OR=2.37, 95%CI: 1.41, 3.97) were the main factors influencing the outpatient health service utilization among patients of pneumoconiosis combined with tuberculosis. Conclusion The outpatient rate of patients of pneumoconiosis combined with tuberculosis is higher than that of patients of pneumoconiosis without tuberculosis. The utilization of outpatient services is related with disease factors and socio-economic security factors.