Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective To investigate the effect of XUE Ji's morning-evening supplementing method,a therapy by tonification according to the alteration of daily yang-qi in the human body and the nature proposed by practitioner XUE Ji in Ming Dynasty,combined with Seretide on exercise endurance in patients with stable chronic obstructive pulmonary disease(COPD)of lung and kidney deficiency type.Methods Ninety-two patients with stable COPD of lung and kidney deficiency type were randomly divided into treatment group and control group,with 46 cases in each group.The control group was given inhalation of Salmeterol/Fluticasone Inhalation Powder(Seretide),and the treatment group was treated with Buzhong Yiqi Pills in the morning and Liuwei Dihuang Pills at evening on the basis treatment for the control group.The course of treatment covered 3 months.The changes of the scale scores of traditional Chinese medicine(TCM)syndrome and St Georges respiratory questionnaire(SGRQ)for quality of life,the distance of 6-minute walking test(6MWT)for exercise endurance,and pulmonary function indicators of forced expiratory volume in one second(FEV1),forced vital capacity(FVC)and their ratio(FEV1/FVC)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and the incidence of adverse reactions were compared between the two groups.Results(1)During the trial,a total of 3 cases were lost,and a total of 89 patients were eventually included,including 45 cases in the treatment group and 44 cases in the control group.(2)After 3 months of treatment,the total effective rate of the treatment group was 82.22％(37/45),and that of the control group was 72.73％(32/44).The intergroup comparison by chi-square test showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the scores of TCM syndromes in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the decrease in the treatment group was more significant than that in the control group(P＜0.01).(4)After treatment,the lung function indicators of FEV1,FVC and FEV1/FVC in the two groups were significantly improved compared with those before treatment(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the scores of SGRQ items of respiratory symptoms,disease impact and activity limitation in the two groups were significantly lower than those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group,the differences being statistically significant(P＜0.01).(6)After treatment,the 6MWT distance of the two groups was significantly improved compared with that before treatment(P＜0.01),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.01).(7)During the treatment,no abnormal changes in the indicators of blood routine test,liver and kidney function,electrocardiogram,and urine and stool routine were found in the two groups.Conclusion XUE Ji's morning-evening supplementing method combined with Seretide exert certain effect in treating stable COPD patients with lung and kidney deficiency syndrome.The therapy can effectively alleviate the clinical symptoms ofnd improve the lung function,exercise endurance and quality of life of the patients,with high safety.

Objective To investigate the differentiation of oligodendrocyte precursor cells after neural injury utilizing Sox10 cell lineage tracing in the cortical tissue.Methods C57BL/6 mice and Sox10-CreERT2/red fluorescent protein(RFP)model mice were used in the current study.The Sox10-CreERT2/RFP model mice generated by crossing Sox10-CreERT2 and Ai9 were 8-week-old F1 mice(n=16),which were randomly divided into control group(n=4)and 7 days(n=4),14 days(n=4),and 30 days feed groups(n=4).Tamoxifen(TAM)was used to induce the expression of RFP.The control group received tamoxifen dissolved in sunflower seed oil by gavage(40 mg/kg once daily for three consecutive days)and the brain tissues were obtained after 4 days.The feed group mice were fed with tamoxifen-containing feed to induce RFP expression,and the brain tissues were obtained after 7,14,and 30 days,respectively.Immunofluorescent staining was performed to detect the expressions of neuronal nuclei(NeuN),microtubule-associated protein 2(MAP2),phosphorylated histone 2AX(γ-H2AX),cluster of differentiation 13(CD 13),γ-aminobutyric acid(GABA),glial fibrillary acidic protein(GFAP),cluster of differentiation 11b(CD11b),vesicular glutamate transporter 2(VGLUT2),and adenomatous polyposis coli(APC,CC-1)in the brains of each group mice.The number of positive cells was counted,and the proportion was calculated.Eight-week-old male C57BL/6 mice were randomly divided into wild type(WT)group(n=4)and WT+TAM group(n=4).They were fed with regular feed and tamoxifen-containing feed for 30 days,respectively,and then brain tissues were obtained.Immunofluorescent double-labeling was used to detect the expressions of γ-H2AX positive neurons in the cortex of mice in both groups.Results In the control group,feed 7 days,14 days,and 30 days groups,the proportions of RFP+pericytes among all RFP+cells in the cortical tissue were(0.8±0.1)％,(2.7±0.1)％,(3.2±0.1)％,(4.0±0.1)％,respectively,and the proportion of mature oligodendrocytes(CC-1+RFP+)in the feed 7 days group was(51.2±0.7)％.The proportions of RFP-positive neurons in the cortex after 14 and 30 days of tamoxifen feed were(0.7±0.1)％and(1.5±0.1)％,respectively,while no conversion to RFP-positive neurons was observed in the gavage group and 7 days feed group.RFP cells in the cortex of the 7 days or 30 days feed group did not express GFAP or CD11b.Extensive γ-H2AX+NeuN+staining was observed in the WT group and WT+TAM group.Conclusion Long-term administration of tamoxifen can promote the differentiation of Sox10 cells into pericytes and neurons.Further investigation into the role of OPC in the neurovascular unit repair mechanism may contribute to a better understanding of the pathogenesis underlying AD.

The clinical manifestations of cow's milk protein allergy (CMPA) in neonates are non-specific and involve multiple organ systems. CMPA may also adversely affect physical growth and central nervous system development in neonates,lead to functional disorders,and increase anxiety and stress among family members. Due to the lack of specific clinical manifestations and diagnostic methods,the diagnosis and management of CMPA in neonates continue to pose significant clinical challenges. To facilitate standardized diagnosis and treatment of CMPA in neonates,the Neonatology Group of the Pediatric Branch of the Chinese Medical Association and the Editorial Committee of the Chinese Journal of Pediatrics have jointly developed the "Expert Consensus on Diagnosis and Management of Neonatal Cow's Milk Protein Allergy (2023)". This article presents and interprets the key points of the consensus regarding dietary and nutritional management of CMPA in neonates.

The mammalian cell nucleus is highly structured and organized into various membrane-less nuclear compartments called nuclear bodies. Nuclear bodies are highly dynamic structures, with a variety of substances gathered inside to promote the more efficient conduct of certain biological reactions. It dynamically produces responses under different biological processes and stress conditions such as tumorigenesis, apoptosis, antiviral defense, and plays an important role in regulating cell homeostasis. Tumor is a major public health problem, and finding new targets is the key to tumor therapy. How the nuclear bodies are involved in the development of tumor has not been reported. This review aims to provide a new understanding of how the nuclear bodies regulates tumor progression and provide a new effective strategy for tumor prevention and treatment.

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.
Humans ; Coronary Artery Disease/complications* ; Coronary Angiography ; Drug-Eluting Stents/adverse effects* ; Treatment Outcome ; Percutaneous Coronary Intervention/methods* ; Ultrasonography, Interventional/methods* ; Risk Factors ; Myocardial Infarction/etiology*

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.