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.

ObjectiveTo 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）. MethodsThe 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. ResultsIn 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］. ConclusionsPatients 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 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.

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.

BACKGROUND:Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents.The radiation destroys the repair mechanism,resulting in delayed or prolonged wound healing.It still lacks an effective therapeutic strategy currently. OBJECTIVE:To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury,which are designed to be antibacteria,promoted healing and analgesics. METHODS:Using levofloxacin,fibroin and lidocaine hydrochloride as raw materials,3D bioprinting technology was applied to prepare the multifunctional wound dressing.(1)The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa,and incubated at 37 ℃ overnight to detect the diameter of the antibacterial zone.(2)40 Kunming mice were randomly divided into trauma group,radiation and trauma model group,treatment group and positive drug group,with 10 mice in each group.Mice in the radiation and trauma model group,treatment group and positive drug group were irradiated by 60Co gamma rays.After 1 hour of radiation,a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups.Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group.Trethanolamine cream was applied to the wounds of the positive drug group.Multifunctional dressing was applied to the wounds of the treatment group.The dressing was changed every 2 days,and the treatment was continued for 14 days.Wound healing rate and serum interleukin-6 level were measured at 3,7 and 14 days after wound modeling.14 days after the wound modeling,the skin tissue of the wound was obtained and received hematoxylin-eosin staining,Masson staining and cytokeratin-14 immunohistochemical staining. RESULTS AND CONCLUSION:(1)3D-printed multifunctional wound dressing had good antibacterial activity.The antibacterial zone diameters against Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa were(4.15±0.09),(4.18±0.23)and(4.35±0.13)cm,respectively.(2)With the extension of modeling time,the wound healed gradually.The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3,7 and 14 days after modeling(P<0.01,P<0.001).The wound healing rate of the treatment group was higher than that of the positive drug group.With the extension of modeling time,the serum interleukin level of mice increased first and then decreased.The serum interleukin level in the treatment group at 3,7 and 14 days after modeling was lower than that in the radiation and trauma model group.Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group,and the dermal collagen fibers were densely arranged.The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group.In the treatment group,normal skin mucosal tissue was observed,the epidermis was arranged closely,and the sweat glands,hair follicles and dermal collagen fibers were arranged regularly.In the positive drug group,the arrangement of epidermal layer was tight,and the arrangement of sweat glands,hair follicles and dermal collagen fibers was regular.Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups(P<0.01,P<0.001).(3)The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia,anti-infection and promoting healing.

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.

With the rapid development of social economy， the number of patients with nervous system diseases has increased， and the incidence of the population has a trend of younger， which has a serious impact on life health and social economy. Artemisinin is an active antimalarial component extracted and isolated from Artemisia annua， a Chinese medicinal material. Artemisinin and its derivatives， in addition to the antimalarial effect， also have anti-parasitic， anti-fungal， anti-viral， hypoglycemic， hypolipidemic， anti-tumor， and anti-inflammatory effects， showing a wide range of pharmacological activities. In the past five years， research on the new pharmacological effects of artemisinin and its derivatives has been deepening， and the efficacy of artemisinin and its derivatives in nervous system diseases has attracted much attention， including anti-neuroinflammation， anti-oxidative stress， maintaining the stability of the blood-brain barrier， regulating the release of neurotransmitters， repairing neuronal damage， and promoting neuronal regeneration. These pharmacological effects indicate that artemisinin and its derivatives are potentially capable of neuroprotection. By sorting out literature on the pharmacological activity of artemisinin and its derivatives in nervous system during 2019－2024， this paper systematically summarized the protective effects of artemisinin and its derivatives against nervous system diseases such as stroke， neurodegenerative diseases， neuroimmunological diseases， neuralgia， and nervous system tumors. This review is expected to provide clues and evidence for new indication expansion of artemisinin drugs， innovative drug development， and clinical treatment of nervous system diseases.

The impact of air pollution on human health has always been a research hotspot in the global health field. Outdoor air pollutants composed of multiple components can enter the human body through various pathways. Cardiovascular diseases are a group of diseases caused by outdoor air pollutants. Studies have shown that the incidence of cardiovascular diseases， including hypertension， arrhythmia， and heart failure， is significantly increased among people exposed to air pollution environments. Air pollutants such as fine particulate matter， nitrogen dioxide， ozone， carbon monoxide， and sulfur dioxide are closely related to the occurrence of cardiovascular diseases， and short-term and long-term exposure causes different cardiovascular risks. By reviewing the relevant research reports from 2019 to 2024， this article summarizes the epidemiological evidence of cardiovascular diseases caused by different air pollutants. It generalizes the pathways through which air pollutants accelerate the progression of cardiovascular diseases. These pathways include oxidative stress， inflammatory response， thrombosis， extracellular vesicle release， endoplasmic reticulum stress， apoptosis， endothelial dysfunction， autonomic nervous system imbalance， and their interactions. Based on the different mechanisms of air pollution on cardiovascular diseases， the article analyzes the main progress in drug intervention and summarizes the roles of various active ingredients and compound prescriptions of traditional Chinese medicine in treating air pollution-related cardiovascular diseases， providing reference for the research on the mechanisms and drug interventions of air pollution-related cardiovascular diseases.

The complex pathophysiological mechanisms between diabetes mellitus and cardiovascular diseases have not yet been fully elucidated， becoming one of the challenges in clinical care. Glucagon-like peptide-1 receptor agonist （GLP1-RA） and sodium glucose cotransporter-2 inhibitors （SGLT2） are clinically used to reduce the cardiovascular risk of patients with diabetes mellitus. Traditional Chinese medicine has diverse biological activities and unique advantages in the treatment of chronic complex diseases due to its multi-component and multi-target effects. Based on recent reports， this paper reviewed the common risk factors of diabetes mellitus and cardiovascular diseases （e.g.， hyperglycemia， insulin resistance， and inflammation）， related targets such as apolipoprotein C-Ⅲ （APOC3）， S100 calcium-binding protein A8/A9 （S100A8/A9）， growth/differentiation factor-15 （GDF-15）， and NACHT， LRR， and PYD domains-containing protein 3 （NLRP3）， advanced glycation end products， insulin resistance， endothelial dysfunction， endoplasmic reticulum stress， mitochondrial dysfunction， and intestinal flora disorder. In addition， this paper summarized the research progress in the treatment of cardiovascular diseases in diabetes mellitus with the active ingredients （e.g.， baicalein， puerarin， curcumin， notoginsenoside， and tanshinone Ⅱ_A）， single herbal medicines （e.g.， Astragali Radix， Ginseng Radix et Rhizoma， Sophorae Flavescentis Radix， Cinnamomi Cortex， and Corni Fructus）， and compound formulas （e.g.， Buzang Tongluo Fang， Yiqi Yangyin Huoxue Fang， Shenqi Fang， Huangqisan， Danggui Buxue Tang， and Liuwei Dihuang Wan） of traditional Chinese medicine. Traditional Chinese medicine mainly treats cardiovascular diseases in diabetes mellitus by reducing inflammation and oxidative stress， ameliorating dyslipidemia and insulin resistance， protecting islet β cell function， repairing endothelial damage， inhibiting smooth muscle cell proliferation， foam cell formation， macrophage polarization， and cardiac hypertrophy and fibrosis， and regulating intestinal flora disorder. These processes involve insulin receptor substrate/ phosphatidylinositol 3-kinase/protein kinase B （IRS/PI3K/Akt）， peroxisome proliferator-activated receptor α/γ （PPAR α/γ）， nuclear factor-kappa B （NF-κB）， adenosine 5′-monophosphate （AMP）-activated protein kinase （AMPK）， hypoxia-inducible factor-1-BCH domain-containing protein （HIF-1-BNIP）， vascular endothelial growth factor/hypoxia-inducible factor-1α （VEGF/HIF-1α） and other signaling pathways. This review is expected to provide a theoretical basis and reference for the treatment of cardiovascular diseases in diabetes mellitus with traditional Chinese medicine.

[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.