Objective: To analyze the expression of sigma factor in drug resistance gene mutations of Mycobacterium tuberculosis (MTB), so as to provide a reference for the drug resistance mechanism of tuberculosis. Methods: Clinical sputum specimens of outpatients at Tianjin Center for Tuberculosis from 2018 to 2022 were collected. A total of 899 MTB-positive strains were obtained by culture, and 492 phenotypically sensitive strains and 407 phenotypically resistant strains were identified by an in vitro phenotypic drug susceptibility test. Thirty drug-sensitive strains of MTB were randomly selected, and 98 drug-resistant strains with specific resistance phenotypes were chosen; all were subjected to melting curve analysis for detection of drug-resistance gene mutations. The strains were divided into sensitive strains without gene mutation, isoniazid-resistant strains with inhA mutation or katG mutation, rifampicin-resistant strains with rpoB mutation, and multigene mutation-resistant strains with inhA+rpoB mutation or katG+rpoB mutation. The mRNA relative expression of sigma factor was detected by fluorescence quantitative PCR, and the ratio of sigma factor mRNA relative expression between the experimental strain and the standard strain >2 was used to screen for highly expressed sigma factor. The differences in sigma factor mRNA relative expression and high expression rate between drug-resistant gene mutant strains and sensitive strains were analyzed. Results: Thirty sensitive strains and 90 drug-resistant strains were included. Among them, there were 16 strains with inhA mutation, 22 strains with katG mutation, 13 strains with rpoB mutation, 15 strains with inhA+rpoB mutation, and 24 strains with katG+rpoB mutation. Compared to the sigma factors of the sensitive strains, the mRNA expression levels of sigG and sigI in inhA-mutated strains, sigF, sigG, sigH, sigI, sigJ, and sigL in katG-mutated strains, and sigF, sigG, sigH, sigJ, and sigL in rpoB-mutated, inhA+rpoB-mutated, and katG+rpoB-mutated strains were significantly higher (all P<0.05). Additionally, the high-expression rates of sigI in inhA-mutated strains, sigF, sigG, sigI, sigJ, and sigL in katG-mutated and inhA+rpoB-mutated strains, and sigF, sigG, sigH, sigJ, and sigL in rpoB-mutated and katG+rpoB-mutated strains were also higher (all P<0.05). Conclusion Compared to sensitive MTB strains, sigI showed higher relative expression of mRNA and high-expression rate in inhA-mutated strains, and sigF, sigG, sigJ, and sigL had higher mRNA relative expression and high-expression rates in katG-mutated, rpoB-mutated, and multi-drug-resistant strains.

Objective: To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis (VVC) caused by Candida albicans. Methods: Temperature-sensitive in situ gels (ISG) were prepared using poloxamers 407 and 188 as matrices. The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29°C and gelation time of 2.5 min. Results: Electroporation increased the transmucosal permeability of the model drug, doxorubicin and improved the antifungal effects of curcumin. In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG. In vivo pharmacodynamic experiments showed that, compared to the model group, curcumin ISG with electroporation inhibited the growth of C. albicans, alleviated vaginal mucosal edema, and reduced the inflammatory response. Conclusion Curcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.

Aim To analyze the incidence of major adverse cardiovascular and cerebrovascular events(MACCE)in patients with different types of acute coronary syndrome(ACS)undergoing coronary artery rotational atherec-tomy(RA)within two years.Methods 268 patients with ACS who underwent RA in the Department of Cardiology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School of Nanjing University,between November 2011 and December 2022 were retrospectively included.According to whether ST-segment elevation myocardial infarction(STEMI)occurred,they were divided into 25 cases in the ST-segment elevation myocardial infarction(STEMI)group and 243 cases in the non-ST-segment elevation acute coronary syndrome(NSTE-ACS)group.The NSTE-ACS group included unstable angina pectoris(UAP)and non-STEMI(NSTEMI).The basic information and intraoperative data related to percutaneous coronary intervention(PCI)in the two groups were collected,and the occurrence of MACCE(including car-diovascular death,non fatal myocardial infarction,worsening heart failure,ischemic stroke and target vessel revasculariza-tion)within two years after RA was followed up and analyzed.Results Compared with the NSTE-ACS group,the STEMI group had a higher incidence of MACCE and cardiovascular mortality during the two-year follow-up period(10.3％and 0.4％vs.28.0％and 8.0％;P＜0.05).There was no statistical difference between the incidence of target vessel revascularization,nonfatal infarction,ischemic stroke and worsening heart failure between the two groups(P＞0.05).According to subgroup analysis based on enrollment periods,the results showed that over time(2011-2017 compared to 2018-2022),the incidence of MACCE in all patients within two years after RA showed a decreasing trend(18.97％vs.6.58％).Combined with previous studies,gender,hypertension,diabetes,renal insufficiency,smoking and left ven-tricular ejection fraction(LVEF)were included in the Cox regression model.It was found that the use of intravascular ul-trasound(IVUS)was an independent factor to reduce the incidence of MACCE in ACS patients within two years after RA(HR=0.333,95％CI:0.153～0.723,P＜0.01).Kaplan-Meier analysis showed that among ACS patients undergoing RA,the cumulative incidence of MACCE events was higher in the STEMI group than that in the NSTE-ACS group(P＜0.05).Conclusion STEMI patients have a higher incidence of MACCE and cardiovascular mortality within two years after RA compared to NSTE-ACS patients,and the use of IVUS during RA surgery can reduce the incidence of MACCE in ACS patients after RA.

Aim To analyze the incidence of major adverse cardiovascular and cerebrovascular events(MACCE)in patients with different types of acute coronary syndrome(ACS)undergoing coronary artery rotational atherec-tomy(RA)within two years.Methods 268 patients with ACS who underwent RA in the Department of Cardiology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School of Nanjing University,between November 2011 and December 2022 were retrospectively included.According to whether ST-segment elevation myocardial infarction(STEMI)occurred,they were divided into 25 cases in the ST-segment elevation myocardial infarction(STEMI)group and 243 cases in the non-ST-segment elevation acute coronary syndrome(NSTE-ACS)group.The NSTE-ACS group included unstable angina pectoris(UAP)and non-STEMI(NSTEMI).The basic information and intraoperative data related to percutaneous coronary intervention(PCI)in the two groups were collected,and the occurrence of MACCE(including car-diovascular death,non fatal myocardial infarction,worsening heart failure,ischemic stroke and target vessel revasculariza-tion)within two years after RA was followed up and analyzed.Results Compared with the NSTE-ACS group,the STEMI group had a higher incidence of MACCE and cardiovascular mortality during the two-year follow-up period(10.3％and 0.4％vs.28.0％and 8.0％;P＜0.05).There was no statistical difference between the incidence of target vessel revascularization,nonfatal infarction,ischemic stroke and worsening heart failure between the two groups(P＞0.05).According to subgroup analysis based on enrollment periods,the results showed that over time(2011-2017 compared to 2018-2022),the incidence of MACCE in all patients within two years after RA showed a decreasing trend(18.97％vs.6.58％).Combined with previous studies,gender,hypertension,diabetes,renal insufficiency,smoking and left ven-tricular ejection fraction(LVEF)were included in the Cox regression model.It was found that the use of intravascular ul-trasound(IVUS)was an independent factor to reduce the incidence of MACCE in ACS patients within two years after RA(HR=0.333,95％CI:0.153～0.723,P＜0.01).Kaplan-Meier analysis showed that among ACS patients undergoing RA,the cumulative incidence of MACCE events was higher in the STEMI group than that in the NSTE-ACS group(P＜0.05).Conclusion STEMI patients have a higher incidence of MACCE and cardiovascular mortality within two years after RA compared to NSTE-ACS patients,and the use of IVUS during RA surgery can reduce the incidence of MACCE in ACS patients after RA.

[Objective]To investigate and explore the characteristics and influencing factors of glucose metabolism in children with β-thalassemia major(β-TM)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).[Methods]The follow-up data of 41 patients with β-TM who underwent HSCT at Hematopoietic Stem Cell Transplantation Department of Children's Medical Center of Sun Yat-sen Memorial Hospital,Sun Yat-sen University were retrospectively analyzed.Their glucose metabolism characteristics were evaluated through laboratory tests and the related influencing factors were analyzed.[Results]In the study,41.46％(17/41)of patients developed abnormal glucose homeostasis after HSCT.Among them,82.35％(14/17)characterized by insulin resistance,but no cases of diabetes mellitus were found.The results of insulin releasing test and oral glucose tolerance test(OGTT)showed that 45.00％(9/20)of patients had abnormal insulin releasing curve and 40.0％(8/20)had delayed serum glucose peak.The average age of HSCT in abnormal glucose homeostasis group was significantly older than that in the normal glucose homeostasis group[(8.8±3.9)years old vs(6.0±3.1)years old,P=0.015].[Conclusions]Patients with β-TM after HSCT may develop abnormal glucose homeostasis,consists largely of insulin resistance.The elder age of HSCT(≥7 years old)is a risk factor for abnormal glucose homeostasis in β-TM patients after HSCT.It is recommended to regularly monitor glucose metabolism indicators in β-TM children after HSCT,especially in elderly transplant recipients.

Objective To explore the changes in the expression of interferon regulatory factor 8(IRF8),a factor regulating macrophage polarization,in stroke rehabilitation and its relationship with cognitive function recovery.Methods This cross-sectional retrospective study included a cohort of patients with acute ischemic stroke treated in our hospital from January 2021 to January 2023.According to the Mini-Mental State Examination score two weeks after stroke,they were divided into post-stroke cognitive impairment(PSCI)group(n=76)and non-PSCI group(n=42).The expres-sion of the IRF8 gene in peripheral blood mononuclear cell(PBMC)was determined using RT-qPCR.The relationship be-tween IRF8 gene expression and cognitive function was studied by a binary logistic regression analysis.Results The ex-pression of IRF8 mRNA in PBMCs in the PSCI group was significantly higher than that in the non-PSCI group(P<0.001).There were significant differences in the proportions of PSCI and non-PSCI patients in the three groups by IRF8 mRNA ter-tiles[T1:53.8%(21/39),T2:64.1%(25/39),T3:75.0%(30/40),χ2=8.082,P=0.018].The logistic regression analy-sis showed that the IRF8 mRNA level>0.024(OR=1.956,P<0.001),age(OR=1.062,P<0.001),National Institutes of Health Stroke Scale(NIHSS)score(OR=1.145,P=0.014),and hemoglobin(OR=1.194,P=0.024)were significantly associated with a higher risk of PSCI.When the cut-off value was 0.01,the area under the curve(AUC)for IRF8 mRNA predicting PSCI was 0.682,with an accuracy of 71.49%,a specificity of 50.24%,and a sensitivity of 71.42%.Including IRF8 mRNA,age,NIHSS score,and hemoglobin into the nomogram,the AUC for PSCI prediction was 0.862.Conclusion The expression of IRF8 mRNA in PBMCs at admission is associated with the development of PSCI in the acute phase of stroke.

Objective To study the influence of long term simulated weightlessness on occurrence of laryngopharyngeal reflux(LPR)in healthy volunteers by detection of pepsin in saliva.Methods During a 90-day head-down tilt bed rest(HDTBR)experiment,11 volunteers(4 from the control group and 7 from the countermeasure group)were recruited in the study in the following seven sessions:before bed rest session(Pre),during bed rest sessions for 3 days(BR3),31 days(BR31),61 days(BR61),85 days(BR85)and post bed rest sessions for 7 days(R7)and 25 days(R25).During each testing session,saliva samples were collected for two consecutive days both in the morning and at night before sleeping.Then pepsin in the saliva was measured by enzyme-linked immunosorbent assay.Scale of otorhinolaryngological symptoms for the duration of"Pre-,During-and Post-"were retrospectively performed.Results Among 288 saliva samples of 11 volunteers,17 saliva samples of 8 volunteers were positive for pepsin.The incidence of LPR was 9.1%(1/11)in the Pre session,and it increased to 36.4%in the BR31 session which was higher than the following consequential sessions(0%in BR31,27.3%in BR61 and 27.3%in BR85).Intriguingly,it rose again to 45.5%in R7 session and decreased to 9.1%until in R25 session.There was no significant difference between the control group and the countermeasure group.Total scores for the scale of otorhinolaryngological symptoms showed that a slight elevation tendency emerged during HDTBR session,compared with the pre-HDTBR session.It recovered during the post bed rest sessions.Conclusion The laryngopharyngeal reflux was found in the Pre,During and Post HDTBR experiment.The incidence was significantly increased both in the BR3 and R7 sessions,which indicates that the change of the posture with the stimulation of gastrointestinal dynamic conditions,despite the changes from vertical to horizontal or from horizontal to vertical,might be the major impact factor contributing to the elevation tendency of the incidence of laryngopharyngeal reflux.

Objective:To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence tomography(OCT). We also investigated the potential association between cholesterol crystals with plaque rupture and healed plaque at non-culprit segment.Methods:This study was a retrospective cohort study. Between January 2017 and December 2017, patients with AMI who underwent 3-vessel OCT imaging were included in this study. Patients were divided into two groups according to the presence or absence of cholesterol crystals at the non-culprit lesions. All patients underwent coronary angiography and OCT examination, and non-culprit plaque characteristics were compared between the two groups. The generalized estimating equation log-binomial multirariate regression model was used to assess the relationship between non-culprit lesions with cholesterol crystals and plaque rupture and plaque healing. The follow-up data collection ended in October 2023. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the cumulative incidence of major adverse cardiovascular events between the two groups.Results:A total of 173 AMI patients were included (aged (56.8±11.6) years; 124 men (71.7%)). Among 710 non-culprit lesions identified by OCT, there were 102 (14.4%) in cholesterol crystals group and 608 (85.6%) in non-cholesterol crystals group. Compared with non-culprit lesions without cholesterol crystals, those with cholesterol crystals had smaller minimum lumen diameter, severer diameter stenosis, and longer lesion length (all P<0.01). The prevalence of plaque rupture (17.6% (18/102) vs. 4.9% (30/608), P=0.001) and thin-cap fibroatheroma (31.4% (32/102) vs. 11.5% (70/608), P<0.01) was higher in the cholesterol crystals groups than in the non-cholesterol crystals group. In addition, vulnerable plaque characteristics such as (44.1% (45/102) vs. 25.8% (157/608), P<0.01), macrophages were more frequently observed in non-culprit lesions with cholesterol crystals. The generalized estimating equation log-binomial multivariate regression analyses showed that non-culprit cholesterol crystals were positively correlated with healed plaque ( OR=1.583, 95% CI: 1.004-2.495, P=0.048). Conversely, cholesterol crystals were not associated with plaque rupture ( OR=1.632, 95% CI: 0.745-3.576, P=0.221). The follow-up time was 2 142 (1 880, 2 198) days. Non-culprit cholesterol crystals were not related to the major adverse cardiovascular events in patients with AMI (log-rank P=0.558). Conclusions:Among AMI patients, non-culprit lesions with cholesterol crystals presented with severer luminal stenosis and increased plaque vulnerability. The presence of non-culprit cholesterol crystals was associated with rather than plaque rupture.

[Objective]Depression is a common mental illness with a profound impact on physical health.Depression has been associated with a higher risk of bacterial infection;however,whether this relationship is causal and how depression affects infection remains unclear.Therefore,we aimed to investigate the effects of depressive phenotype in infected mice by constructing a chronic unpredictable mild stress(CUMS)model.[Methods]Mice were induced with CUMS for 4 weeks.The depressive phenotype was evaluated using behavioral tests.Subsequently,the mice were intraperitoneally injected with Klebsiella pneumoniae to establish bacterial infection.Serum and abdominal tissues were collected 48 h after infection.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the tissues,and enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of inflammatory factors.In addition,the fecal samples collected before infection were analyzed for 16S rDNA gene of gut microbiota,and the expression levels of NF-κB/NLRP3 signaling pathway in colon tissues of uninfected mice were detected.[Results]Behavioral tests showed that compared with the control mice,CUMS mice had significantly lower body weight(P<0.0001,t=5.426),lower sucrose preference rate(P<0.001,t=4.937),increased swimming stationary time(P<0.001,t=16.37),and decreased time spent in the central area of the open field(P<0.01,t=3.575).Survival analysis showed that compared with the control mice,the survival rate of CUMS mice significantly decreased after infection(P<0.05).Additionally,histochemical staining showed that tissue damage in the liver(P<0.05,t=4.025),kidney(P<0.05,t=2.828),and mesentery(P<0.01,t=5.367)significantly increased.Furthermore,ELISA results showed that the levels of the inflammatory cytokines IL-6(P<0.01,t=3.365),IL-1β(P<0.01,t=4.061),TNF-α(P<0.01,t=4.460)and LPS(P<0.0001,t=27.24)were elevated.The difference was statistically significant.According to 16S rDNA sequencing,CUMS-induced changes in the intestinal bacterial community structure of mice,making them significantly different from the control mice.Compared with the control mice,the expression levels of NF-κB(P<0.01,t=6.825)and NLRP3(P<0.001,t=9.561)were upregulated in CUMS mice.[Conclusion]The CUMS model was successfully constructed and CUMS mice developed more severe bacterial infection.Gut microbiota was dysregulated and the expression of NF-κB/NLRP3 signaling pathway was up-regulated in CUMS mice,which was related to the susceptibility to bacterial infection.

Objective: To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder (PTSD), and to improve efficacy and patient compliance. Methods: In this study, we used ginger oil, a phytochemical with potential therapeutic properties, to prepare ginger oil patches. High-performance liquid chromatography (HPLC) was used to quantify the main active component of ginger oil, 6-gingerol. Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers, including their type and concentration. Subsequently, the ginger oil patches were optimized and subjected to content determination and property evaluations. A PTSD mouse model was established using the foot-shock method. The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections, behavioral tests, and the evaluation of biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and melatonin (MT). Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels. Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day, addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy. Conclusions Ginger oil can be prepared as a transdermal drug patch that meets these requirements, and the bioavailability of the prepared patch is better than that of oral administration. It can improve PTSD with good patient compliance and ease of administration. Therefore, it is a promising therapeutic formulation for the treatment of PTSD.