ObjectiveTo investigate the current status of latent tuberculosis infection (LTBI) among the elderly population in rural areas of Changxing County, Zhejiang Province, and to provide an evidence for the development of LTBI prevention and control measures. MethodsBetween January and May 2024, elderly individuals participating in urban and rural residents’ health checkups were screened for Mycobacterium tuberculosis infection using a domestically produced interferon-γ release assay (IGRA) kit. Individuals tested positive by IGRA but without active tuberculosis were classified as LTBI cases. The prevalence of LTBI among the participants was subsequently analyzed. ResultsAmong the 6 765 subjects, 637 tested positive by IGRA, including one identified active tuberculosis patient, resulting in a LTBI prevalence rate of 9.40%. There was a statistically significant difference in positivity rates across different IGRA methodologies (χ²=35.530, P<0.001). Higher LTBI rate was observed in males, individuals with a history of diabetes mellitus, and those with a history of pulmonary tuberculosis, exhibiting statistically significant differences (χ²=32.401, P<0.001; χ²=5.789, P=0.020; χ²=39.248, P<0.001, respectively.) No statistically significant difference in LTBI rate was found across different age groups (χ²=0.238, P=0.971). ConclusionThe prevalence of LTBI among the elderly rural residents in Changxing County is relatively low. Male, individuals with a history of diabetes mellitus, and those with a history of pulmonary tuberculosis have an increased risk of LTBI, warranting targeted risk monitoring and timely interventions.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective To analyze the metabolomics characteristics of chronic atrophic gastritis(CAG)patients with liver-stomach qi stagnation and spleen-stomach weakness syndromes based on non-targeted metabolomics technology,and to identify the serum differentiated metabolites related to traditional Chinese medicine(TCM)syndrome of CAG patients,so as to provide a reference for the objectification of syndrome differentiation.Methods Sixty patients with CAG were included,including 30 cases of liver-stomach qi stagnation syndrome and 30 cases of spleen-stomach weakness syndrome.Fasting blood of 5 mL was collected from the cubital vein of patients in the two groups,and the serum levels of metabolites were detected by ultra-high-performance liquid chromatography-mass spectrometry(UPLC-MS)methods.The principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and cluster analysis were used to screen the differentiated metabolites of CAG patients with liver-stomach qi stagnation syndrome and spleen-stomach weakness syndrome.Finally,metabolite pathway analysis was performed for the obtained differentiated metabolites using the KEGG database.Results The results for the screening of differentiated metabolites showed that significant differences of amino acid derivatives and small peptide metabolites were presented between CAG patients with liver-stomach qi stagnation syndrome and CAG patients with spleen-stomach weakness syndrome.The amino acid derivatives consisted of N-acetylglycine,histamine,O-phosphoserine,selenomethylselenocysteine,and methyl-tyrosine.And the small peptide metabolites consisted of tyrosine-leucine-phenylalanine,histidine-alanine-glutamate-lysine,L-asparagine-L-proline-L-serine,and L-isoleucine-L-isoleucine.Conclusion Differences in amino acid metabolism exist between CAG patients with liver-stomach qi stagnation syndrome and those with spleen-stomach weakness syndrome,and metabolites such as N-acetylglycine,intermethyltyrosine,and O-phosphoserine may be the potential biomarkers for distinguishing liver-stomach qi stagnation syndrome from spleen-stomach weakness syndrome in CAG patients.

Objective:To investigate the regulatory effect of transient receptor potential cation channel subfamily C member 3 (TRPC3) on the retina in oxygen-induced retinopathy (OIR) mice and biological behavior of human retinal vascular endothelial cells (HREC).Methods:A total of 32 healthy SPF grade 7-day-old C57BL/6 mice were selected and randomly divided into a control group and an OIR group by the random number table method, with 16 mice in each group.The control group received no special treatment, and the OIR model was established in the OIR group.On postnatal day 17 (PN17), the success of the model establishment was verified by immunofluorescence staining of the retinal patch.The in vitro cultured HREC were divided into a normal control group, a transfection reagent group, and a si-TRPC3 group.The normal control group received no special treatment, while the transfection reagent group and the si-TRPC3 group were transfected with transfection reagent or transfection reagent + si-TRPC3.The relative expression of TRPC3 mRNA was detected by real-time quantitative fluorescence PCR.The relative expressions of TRPC3, transcription factor NF-E2 related factor (Nrf2), and superoxide dismutase (SOD) proteins were determined by Western blot.HREC were further divided into a normal control group, a vascular endothelial growth factor (VEGF) group, a si-TRPC3 group, and a Pyr3 (TRPC3 channel inhibitor) group, which were cultured in complete medium, medium containing 20 ng/ml VEGF recombinant protein, medium containing 20 ng/ml VEGF recombinant protein (si-TRPC3 transfection for 72 hours), and medium containing 20 ng/ml VEGF recombinant protein+ 1 μmol/L Pyr3 for 48 hours, respectively.The proliferation ability of HREC was detected using cell counting kit 8 (CCK-8). The horizontal and vertical migration ability of cells were detected by cell scratch assay and transwell assay, respectively.This study followed the 3R principles of animal welfare and was approved by the Ethics Committee of Hebei Eye Hospital (No.2023LW04). Results:Pathological neovascular clusters with strong fluorescent staining appeared in the retina of OIR mice on PN17.The relative expressions of TRPC3 mRNA and protein in the retina of OIR mice were 2.057±0.244 and 1.517±0.290, respectively, significantly higher than 0.983±0.033 and 0.874±0.052 of control group ( t=6.165, 3.094; both at P<0.05). The relative expression levels of TRPC3 mRNA and protein were significantly lower, and the relative expression levels of Nrf2 and SOD proteins were higher in the si-TRPC3 group than in the normal control and transfection reagent groups, and the differences were statistically significant (all at P<0.05). The CCK-8 experiment results showed that the cell absorbance value was higher in the VEGF group than in the normal control group, and lower in the si-TRPC3 and Pyr3 groups than in the VEGF group, with statistically significant differences (all at P<0.05). The results of the cell scratch experiment showed that the lateral migration rate of VEGF group cells was higher than that of normal control group, while the lateral migration rate of si-TRPC3 group and Pyr3 group cells was lower than that of VEGF group, and the differences were statistically significant (all at P<0.05). The transwell experiment results showed that the number of stained cells in the VEGF group was higher than that in the normal control group, and the number of stained cells in the si-TRPC3 group and Pyr3 group was lower than that in the VEGF group, with statistically significant differences (all at P<0.05). Conclusions:Hypoxia induces increased TRPC3 expression in OIR mouse retina, and downregulation of TRPC3 inhibits HREC proliferation and migration.The mechanism is related to the activation of the Nrf2-related oxidative stress pathway.

Objective To detect the levels of serum collagen type Ⅰ alpha 1 chain(COL1A1)and collagen type Ⅰ alpha 2 chain(COL1A2)in patients with intracranial aneurysm(IA),and explore their correlations with aneurysm rupture.Methods A total of 110 IA patients admitted to our hospital were regarded as the IA group and another 100 volunteers who underwent physical examination in our hospital were regarded as the control group.The expression levels of serum COL1A1 and COL1A2 were detected by ELISA.The IA patients were divided into the ruptured group(n=66)and unruptured group(n=44)according to the presence or absence of aneurysm rupture,and the clinical data and expression levels of serum COL1A1 and COL1A2 were compared between the two groups.The expression levels of serum COL1A1 and COL1A2 in patients with different Hunt-Hess grades were compared.The risk factors of aneurysm rupture in patients with IA were analyzed by multivariate Logistic regression analysis.The predictive value of serum COL1A1 and COL1A2 for aneurysm rupture in patients with IA were evaluated by receiver operating characteristic(ROC)curve.The correlation of serum COL1A1 and COL1A2 with Hunt-Hess grade for patients in rupture group was analyzed by Spearman correlation analysis.Results The expression levels of serum COL1A1 and COL1A2 for patients in the IA group were significantly higher than those in the control group(P<0.05).The number of patients with hypertension,diabetes mellitus,hyperlipidemia,aneurysm diameter>10 mm,and the expression levels of serum COL1A1 and COL1A2 in the rupture group were significantly more/higher than those in the unruptured group(P<0.05).The expression levels of serum COL1A1 and COL1A2 in patients with Hunt-Hess grades from Ⅲ to Ⅳ were significantly higher than those in patients with grades from Ⅰ to Ⅱ(P<0.05).The expression levels of serum COL1A1 and COL1A2 for patients in the rupture group were positively correlated with Hunt-Hess grade(r=0.562,0.414,P<0.05).Multivariate Logistic regression analysis showed that hypertension,diabetes mellitus,aneurysm diameter>10 mm,and increased expression levels of COL1A1 and COL1A2 were risk factors for aneurysm rupture in IA patients(P<0.05).The area under the curve(AUC)of aneurysm rupture predicted by serum COL1A1 and COL1A2 together was significantly higher than that predicted by COL1A1 alone(Z=1.905,P=0.028)and COL1A2 alone(Z=1.754,P=0.040).Conclusion The increased expression levels of serum COL1A1 and COL1A2 are risk factors for aneurysm rupture in patients with IA,and their combined prediction of aneurysm rupture in IA patients has certain clinical value.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To develop and validate a predictive model of 28-day mortality in sepsis based on lactate dehydrogenase-to-albumin ratio (LAR).Methods:Sepsis patients diagnosed in the department of intensive care medicine of the First Affiliated Hospital of Soochow University from August 1, 2017 to September 1, 2022 were retrospective selected. Clinical data, laboratory indicators, disease severity scores [acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), sequential organ failure assessment (SOFA)] were collected. Patients were divided into death group and survival group according to whether they died at 28 days, and the difference between the two groups was compared. The dataset was randomly divided into training set and validation set according to 7∶3. Lasso regression method was used to screen the risk factors affecting the 28-day death of sepsis patients, and incorporating multivariate Logistic regression analysis (stepwise regression) were included, a prediction model was constructed based on the independent risk factors obtained, and a nomogram was drawn. The nomogram prediction model was established. Receiver operator characteristic curve (ROC curve) was drawn to analyze and evaluate the predictive efficacy of the model. Hosmer-Lemeshow test, calibration curve and decision curve analysis (DCA) were used to evaluate the accuracy and clinical practicability of the model, respectively.Results:A total of 394 patients with sepsis were included, with 248 survivors and 146 non-survivors at 28 days. Compared with the survival group, the age, proportion of chronic obstructive pneumonia, respiratory rate, lactic acid, red blood cell distribution width, prothrombin time, activated partial thromboplastin time, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, blood potassium, blood phosphorus, LAR, SOFA score, and APACHEⅡ score in the death group were significantly increased, while oxygenation index, monocyte count, platelet count, fibrinogen, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and blood calcium were significantly reduced. In the training set, LAR, age, oxygenation index, blood urea nitrogen, lactic acid, total cholesterol, fibrinogen, blood potassium and blood phosphorus were screened by Lasso regression. Multivariate Logistic regression analysis finally included LAR [odds ratio ( OR) = 1.029, 95% confidence interval (95% CI) was 1.014-1.047, P < 0.001], age ( OR = 1.023, 95% CI was 1.005-1.043, P = 0.012), lactic acid ( OR = 1.089, 95% CI was 1.003-1.186, P = 0.043), oxygenation index ( OR = 0.996, 95% CI was 0.993-0.998, P = 0.002), total cholesterol ( OR = 0.662, 95% CI was 0.496-0.865, P = 0.003) and blood potassium ( OR = 1.852, 95% CI was 1.169-2.996, P = 0.010). A total of 6 predictor variables were used to establish a prediction model. ROC curve showed that the area under the curve (AUC) of the model in the training set and validation set were 0.773 (95% CI was 0.715-0.831) and 0.793 (95% CI was 0.703-0.884), which was better than APACHEⅡ score (AUC were 0.699 and 0.745) and SOFA score (AUC were 0.644 and 0.650), and the cut-off values were 0.421 and 0.309, the sensitivity were 62.4% and 82.2%, and the specificity were 82.2% and 68.9%, respectively. The results of Hosmer-Lemeshow test and calibration curve showed that the predicted results of the model were in good agreement with the actual clinical observation results, and the DCA showed that the model had good clinical application value. Conclusion:The prediction model based on LAR has a good predictive value for 28-day mortality in patients with sepsis and can guide clinical decision-making.

Objective:To analyze the individual and cumulative effects of unhealthy lifestyle on the prevalence of hypertension, diabetes and dyslipidemia in old adults in China, and find out the critical lifestyle in the network.Methods:Based on the baseline data of Yunnan Behavior and Disease Surveillance Cohort in 2021, a total of 16 763 older adults aged ≥60 years were included in our study. The unhealthy lifestyle factors including smoking, drinking, unhealthy eating habit, lower physical activity level, abnormal BMI and abnormal waist circumference. We calculated the unhealthy lifestyle score by using the cumulative exposures of each participant. Multiple logistic regression and mixed graphical models were used to describe the association between unhealthy lifestyle and the prevalence of hypertension, diabetes and dyslipidemia.Results:The prevalence of hypertension, diabetes and dyslipidemia were 57.0%, 11.5% and 37.0%, respectively. Most of the unhealthy lifestyles included in the study were risk factors for hypertension, diabetes and dyslipidemia, and the risks of disease increased with the increase of the unhealthy lifestyle score. The participants with the highest score (score: 6) had significantly higher prevalence of hypertension ( OR=3.99, 95% CI: 1.81-8.80), diabetes ( OR=4.64, 95% CI: 1.64-13.15) and dyslipidemia ( OR=4.26, 95% CI: 2.08-8.73) compared with those with lowest score (score: 0). In the network constructed by mixed graphical model, abnormal waist circumference (bridge strength=0.81) and hypertension (bridge strength=0.55) were vital bridge nodes connecting unhealthy lifestyle and hypertension, diabetes and dyslipidemia. Conclusions:The unhealthy lifestyle score was associated with risks for hypertension, diabetes and dyslipidemia. Abnormal waist circumference was the key factor for chronic diseases in old adults.

Objective To investigate the incidence and severity of enamel demineralization during clear aligner treatment and provide reference for clinical medical nursing work.Methods A total of 151 patients(3 507 teeth)undergoing clear aligner treatment in our hospital from 2015 to 2022 were collected.The enamel demineralization before and after treatment was compared,and the enamel demi-neralization index(EDI)was calculated to evaluate the severity of demineralization.The incidence and severity of enamel demineraliza-tion were analyzed statistically,and the differences among different genders,ages and dental positions were compared.Results Enam-el demineralization occurred in 84 patients during treatment,with an incidence rate of 55.63%.Gender and treatment time had no effect on the incidence,and the incidence of adolescent patients was higher than that of adult patients.Among the investigated 3 507 teeth,601 teeth had enamel demineralization,and the incidence rate was 17.14%.The incidence of maxillary anterior teeth and mandibular posterior teeth was higher;the incidence of right teeth was significantly higher than that of left teeth,and the incidence of teeth with ad-hesive attachments was also significantly increased.88%of the enamel demineralization lesions were 1－2 degrees,and the degree of enamel demineralization was similar in male and female patients.But the degree in adolescents was significantly higher than that in adult patients.The average EDI value of maxillary anterior teeth was significantly higher than that of mandible,but that of maxillary posterior teeth was significantly lower than that of mandible.The average EDI value of right teeth was significantly higher than that of left.Conclusion The incidence of enamel demineralization is high in the process of clear aligner treatment,and teenagers are suscep-tible to it.The demineralization of teeth is significantly different among different tooth positions,and adhesive attachments will increase the risk of enamel demineralization.Therefore,medical staff should take active and effective measures in the prevention and treatment of enamel demineralization.

At present,the incidence of breast cancer has been the first in the world,and hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2-)advanced breast cancer has seriously affected the prognosis of patients.In the past,the therapeutic drugs were mainly third-generation aromatase inhibitors(AI)and fulvestrant.In recent years,the era of endocrine therapy combined with cyclin-dependent kinase4/6(CDK4/6)inhibitors has begun.Different CDK4/6 inhibitors have different related adverse events,and they need to evaluate the physical condition of patients and develop a treatment plan,but neutropenia is prevalent.Everolimus,Alpelisib,and Chidamide are second-line therapeutic drugs.