Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

Objective: To investigate the status of tuberculin skin test (TST) results and the influencing factors among student close contacts with pulmonary tuberculosis, so as to provide the evidence for developing prevention and control strategies for pulmonary tuberculosis among students. Methods: The students aged 15 years and above who had close contact with pulmonary tuberculosis cases in Yuecheng District, Shaoxing City, Zhejiang Province, from October 2016 to December 2023 were recruited and investigated using questionnaires and TST to collect demographic information, contact history, and TST results. The influencing factors for TST positivity among student close contacts with pulmonary tuberculosis were analyzed using a multivariable logistic regression model. Results: A total of 5 507 student close contacts were investigated, including 2 982 males and 2 525 females, with a male-to-female ratio of 1.18∶1. The mean age was (19.10±1.71) years. Among them, 397 (7.21%) were technical secondary school students, 766 (13.91%) were senior high school students, 2 556 (46.41%) were junior college students, and 1 788 (32.47%) were college students or above. A total of 958 students tested positive for TST, with a positivity rate of 17.40%. The rates of general positivity, moderate positivity, and strong positivity were 10.53%, 4.98% and 1.89%, respectively. Multivariable logistic regression analysis showed that senior high school students (OR=1.473, 95%CI: 1.009-2.152) and junior college students (OR=1.467, 95%CI: 1.074-2.005), as well as those with an exposure-to-screening interval of ≥46 days (46-<61 days, OR=2.043, 95%CI: 1.478-2.826; ≥61 days, OR=1.291, 95%CI: 1.018-1.637) had a higher risk of TST positivity. Female student close contacts had a lower risk of TST positivity (OR=0.753, 95%CI: 0.649-0.873). Conclusion The TST positivity rate was relatively high, and gender, school type, and exposure-to-screening interval were influencing factors for TST positivity among student close contacts with pulmonary tuberculosis.

Objective:To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins(WTAP)on the cell biological properties of esophageal squamous cell carcinoma(ESCC)cells.Methods:31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected.The esophageal cancer cells KYSE30,KYSE410,KYSE150,KYSE510,TE-1,and normal human esophageal epithelial cells HET-1A were routinely cultured.Transfection reagents were used to transfect si-NC,si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells.The cells were divided into si-NC,si-WTAP#1 and si-WTAP#2 groups.The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay.CCK-8 assay,clone formation assay,and scratch healing assay,Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation,migration,invasion and apoptosis.WB assay was used to detect the expressions of WTAP,MAP3K9,EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP;immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues,immunoprecipitation of methylated RNA(MeRIP)-qPCR assay to detect the level of MAP3K9 m6A in ESCC cells,actinomycin D assay to detect the stability of mRNA of MAP3K9,and database data to analyze the expression,target genes,functional enrichment,and interacting RNA of WTAP.Results:WTAP was highly expressed in ESCC tissues and cells(P<0.05 or P<0.01 or P<0.001)and correlated with the degree of differentiation(P<0.01);the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells(P<0.01 or P<0.001);the knockdown of WTAP significantly inhibited the proliferation,migration and invasion of KYSE150 and KYSE510 cells(P<0.05 or P<0.01 or P<0.001),and promoted the apoptosis of KYSE150 and KYSE510 cells(P<0.05 or P<0.01).Knockdown of WTAP resulted in a significant decrease in the m6A level of MAP3K9(P<0.05),and its mRNA expression level and mRNA stability were both significantly reduced(P<0.05).Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway;the expression levels of MAP3K9,p-ERK,N-cadherin,and MMP9 were significantly reduced(P<0.05 or P<0.01),and the expression level of E-cadherin was significantly elevated(P<0.05 or P<0.01)in the KYSE150 and KYSE510 cells after knockdown of WTAP.Conclusions:WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation.It promotes the stability of MAP3K9 mRNA through m6A modification,activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.

Primary aldosteronism(PA) is the most common endocrine cause of secondary hypertension and is characterized by hypertension, hypokalemia, suppressed renin, and inappropriately elevated aldosterone. Increasing evidence indicates disturbances in calcium homeostasis among patients with PA. The calcium-regulatory system encompasses calcium and phosphate, parathyroid hormone(PTH), and vitamin D. Patients with PA frequently exhibit hypocalcemia, hypophosphatemia, elevated PTH, and reduced vitamin D levels. Clarifying the contribution of calcium dysregulation to PA pathogenesis is clinically relevant for mitigating target-organ damage. This review summarizes: (1) the role of aberrant calcium signaling in the development of PA; (2) characteristic features of calcium homeostasis in PA; and (3) the interactions between the renin-angiotensin-aldosterone system(RAAS) and calcium-regulatory pathways. Overall, abnormalities in calcium signaling appear integral to the pathogenesis of PA, and disrupted calcium homeostasis may aggravate target-organ injury in affected patients.

ObjectiveTo analyze the influencing factors for recurrence in successfully treated pulmonary tuberculosis patients with isoniazid-resistant and rifampicin-sensitive in Shaoxing City, Zhejiang Province. MethodsData on general demographic information, treatment information and drug susceptibility test results for pulmonary tuberculosis patients admitted to the designated tuberculosis medical institutions and registered in the tuberculosis information management system was collected in Shaoxing City from January 2011 to August 2024. A total of 428 patients with isoniazid resistance (including isoniazid single resistance and multiple resistance) but who were successfully treated were included in the study. Information for the recurrence after successful treatment of the patients was analyzed. The Cox proportional hazards models were used to analyze the influencing factors of recurrence in patients. ResultsAmong the 428 successfully treated patients included in the study, 31 cases (accounting for 7.24%) had recurrence by the end of the observation period, with a recurrence rate density of 1.31 per 100 person-years and a median recurrence time of 0.99 (0.08, 8.27) years. Among the relapsed population, 51.61% of the patients relapsed within one year after successful treatment. 77.42% of the patients relapsed within two years after successful treatment. Multivariate Cox regression analysis showed that when isoniazid resistance was discovered, the diagnosis classification of relapse (HR=4.115, 95%CI: 1.734‒9.767) and positive 0-month sequence smear (HR=4.457, 95%CI: 1.053‒18.866) were risk factors for recurrence after successful treatment in patients. ConclusionRegular follow-up should be strengthened for at least two years after the successful treatment of isoniazid-resistant pulmonary tuberculosis patients. Special attention should be paid to the treatment effect and regular re-examination and monitoring after the end of the treatment course of isoniazid-resistant pulmonary tuberculosis patients who have been re-treated and were sputum smear positive at baseline, so as to prevent recurrence and disease progression in high-risk populations.

Primary aldosteronism(PA) is the most common endocrine cause of secondary hypertension and is characterized by hypertension, hypokalemia, suppressed renin, and inappropriately elevated aldosterone. Increasing evidence indicates disturbances in calcium homeostasis among patients with PA. The calcium-regulatory system encompasses calcium and phosphate, parathyroid hormone(PTH), and vitamin D. Patients with PA frequently exhibit hypocalcemia, hypophosphatemia, elevated PTH, and reduced vitamin D levels. Clarifying the contribution of calcium dysregulation to PA pathogenesis is clinically relevant for mitigating target-organ damage. This review summarizes: (1) the role of aberrant calcium signaling in the development of PA; (2) characteristic features of calcium homeostasis in PA; and (3) the interactions between the renin-angiotensin-aldosterone system(RAAS) and calcium-regulatory pathways. Overall, abnormalities in calcium signaling appear integral to the pathogenesis of PA, and disrupted calcium homeostasis may aggravate target-organ injury in affected patients.

Objective:To investigate the clinical characteristics and risk factors for disease progression after treatment in patients with post-tuberculosis chronic pulmonary aspergillosis (post-TB CPA).Methods:A retrospective cohort study was conducted on post-TB CPA patients admitted to Hangzhou Red Cross Hospital between January 2020 and December 2023. The demographic manifestation, clinical manifestation, laboratory indicators, imaging findings, and treatment strategies were collected. Patients were divided into progression group and non-progression group based on treatment outcomes, and the clinical data of the two groups were compared. Chi-square test was used for univariate analysis, and multivariate logistic regression were used to identify independent risk factors for disease progression after treatment.Results:A total of 109 post-TB CPA patients were included, and 33.9%(37/109) were in the progression group and 66.1%(72/109) in the non-progression group. Multivariate logistic regression revealed that subacute invasive aspergillosis (SAIA) (odds ratio ( OR)=14.356, 95% confidence interval ( CI) 2.923 to 70.504, P=0.001), elevated erythrocyte sedimentation rate (ESR) ( OR=5.276, 95% CI 1.505 to 18.491, P=0.009), and pulmonary fibrosis ( OR=5.030, 95% CI 1.437 to 17.612, P=0.012) were independent risk factors for disease progression. Antifungal treatment for ≥3 months was associated with a lower risk of disease progression ( OR=0.038, 95% CI 0.003 to 0.431, P=0.008). The proportion of non-progression group receiving surgical treatment was higher than that of progression group with statistical significance (31.9%(23/72) vs 5.4% (2/37), χ2=8.30, P=0.004), but the protective effect of surgery on disease progression was not confirmed by multivariate analysis ( OR=0.735, 95% CI 0.132 to 4.080, P=0.724). Conclusions:Disease progression in patients with post-TB CPA is strongly associated with SAIA, elevated ESR, and pulmonary fibrosis. Standardized anti-fungal treatment for ≥3 months significantly improves the prognosis.