Factors influencing pathological changes in the liver tissue in hepatitis B virus carriers with low-level viremia.

OBJECTIVES: To investigate the optimal timing for initiating antiviral therapy in hepatitis B virus (HBV) carriers with low-level viremia (LLV). METHODS: We retrospectively enrolled 126 HBV carriers with LLV who underwent liver biopsy. Patients' clinical data, routine blood test results, portal vein diameter, splenic vein diameter and thickness, and measurements (LSM) within 1 week before liver biopsy were obtained. Single-factor and multifactor statistical methods were used to analyze factors that affected inflammation and fibrosis in pathological liver tissues. The receiver operating characteristic curve was used to analyze liver stiffness and HBV DNA levels to determine liver tissue inflammation and fibrosis. R -Studio software was used to draw nomograms, calibration plots, and model decision curves. RESULTS: Infection duration and HBV DNA levels affected liver tissue inflammation. Albumin(ALB), aspartate aminotransferase (AST), HBV DNA, liver stiffness, age, and splenic thickness affected liver fibrosis. The best cutoff value of the LSM for diagnosing liver inflammation and fibrosis was 7.45 (specificity, 92%). The best cutoff value of HBV DNA for diagnosing liver inflammation and fibrosis was 39.5 (specificity, 96%). HBV DNA,and splenic thickness affected the treatment decision in naive chronic hepatitis Bpatients with LLV CONCLUSIONS: HBV carriers with LLV have high incidences of liver tissue inflammation and fibrosis. The infection duration and HBV DNA levels affected liver inflammation whereas the ALB, AST AST levels, HBV DNA, LSM, age, and splenic thickness affected liver fibrosis. Eligible expansion of antiviral treatment indications is necessary, however, a universal treatment approach may be inefficient. HBV DNA can be a reference for initiating antiviral therapy.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Effects of (In)Congruency in Fertility Motivation on Fertility Desire and Intention Among Couples Living with HIV: A Dyadic Approach.

Background: Fertility decision-making plays a negligible role in completing fertility goals among couples living with HIV (CLWH). Being commonly matched concerning fertility motivation seems essential for fertility desire/intention. Few studies report on intra-couple congruences or incongruences in fertility motivation on desire/intention. This study aims to assess the effects of (in)congruency in fertility motivation on fertility desire and intention among couples living with HIV. Methods: This study uses the actor-partner interdependence model (APIM) to assess the independent direct and indirect effect of fertility motivation on intention, and dyadic response surface analysis with congruency/incongruent effect (DRSA) of fertility motivation on intention using fertility desire as mediator variable among CLWH. CLWH were selected from a clinic in Kunming, China, between October and December 2020. Cross-sectional research included 314 CLWH. Results: APIM revealed that the wife's fertility motivation had an indirect influence on fertility intention of couples mediated by her fertility desire (R2 = 0.42). There was a significant effect on fertility intention by interaction of (in)congruency in fertility motivation among couples. DRSA shows that linear congruency in fertility motivation of both husband and wife increased fertility desire and intention of couples. However, if there was an incongruent in fertility motivation among husband and wife, husband's domination in fertility motivation was common and negatively affect the wife's fertility desire to have a child. Overall, couples who were matched on fertility motivation reported a significant greater relationship with fertility intention than couples who were mismatched. Conclusion: Counseling could help both the husband and wife achieve a greater positive fertility intention by addressing comparable fertility goals.

Ethnic disparities in prevalence of chronic non-communicable diseases and its multimorbidity among older adults in rural southwest China.

BACKGROUND: As the population ages, chronic non-communicable diseases (NCDs) multimorbidity has emerged as a major public health issue globally. This study examines ethnic disparities in prevalence of NCDs and its multimorbidity among rural southwest Chinese older adults. METHODS: A cross-sectional survey was conducted in rural southwest population aged ≥ 60 years consisting of 5,642 consenting participants of Han and three ethnic minority groups (Dai, Ha Ni, and Bai). Information about participants' demographic characteristics and lifestyle behaviors was obtained using a standard questionnaire. Anthropometric measurements including height, weight, and waist circumference, fasting blood sugar and blood pressure measurement, as well as post-bronchodilator spirometry test were recorded for each participant. RESULTS: The age-standardized prevalence of five common chronic NCDs- hypertension, diabetes, coronary heart disease (CHD), stroke, chronic obstructive pulmonary disease (COPD) - and its multimorbidity was 72.8%, 15.9%, 4.0%, 10.0%, 9.8%, and 27.6%, respectively. Bai participants had both the highest overall and sex-specific prevalence rates of hypertension, diabetes, stroke, and COPD, whereas Han participants had the highest rates of CHD (P < 0.01). The results of multivariate logistic regression analysis indicated that female and older participants had a higher probability of chronic NCDs multimorbidity than their counterparts (P < 0.01). Bai ethnic minority participants were more likely to have NCDs multimorbidity while Ha Ni and Dai ethnic minority participants were less likely to have NCD multimorbidity relative to the Han participants (P < 0.05). Older adults with a higher level of education and family history of chronic NCDs, and who were also current smokers, current drinkers, obese, centrally obese, and physically inactive had a greater probability of developing chronic NCDs multimorbidity (P < 0.01). CONCLUSIONS: Ethnicity and individual demographic and lifestyle factors significantly impact prevalence of chronic NCDs multimorbidity. Future chronic NCDs prevention and control strategies must be tailored to address ethnicity, and culturally tailored lifestyle interventions may reduce the prevalence of chronic NCDs multimorbidity in rural southwest China.

Inflammation markers and the risk of hypertension in people living with HIV.

Background: The incidence of hypertension is high in people living with HIV (PLWH). High-sensitivity C-reactive protein (hsCRP), systemic inflammation response index (SIRI), and neutrophil-to-monocyte ratio (NMR) are considered economic and convenient parameters that reflect the levels of inflammation in patients. Our aim was to explore whether indirect inflammation markers are associated with hypertension in PLWH. Methods: This was a case-control study. The case group (hypertension) comprised PLWH with hypertension, and the control group (non-hypertension) comprised sex- and age-(± 3 years)-matched PLWH without hypertension. Demographic parameters, hsCRP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune- inflammation index (SII), SIRI, lymphocyte-to-monocyte ratio (LMR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), NMR, time to HIV diagnosis, antiretroviral therapy (ART) duration, recent CD4+ and CD8+ cell counts, recent CD4+/CD8+ ratio, recent HIV viral load (HIV-RNA),and recent ART regimen were obtained from the patients' electronic medical records. A t-test or Wilcoxon rank-sum test was performed to compare differences between the two groups, and conditional logistic regression was used to analyze the risk factors of hypertension. Correlations between inflammation markers and CD4+ cell counts, CD8+ cell counts, and CD4+/CD8+ ratio were analyzed using Spearman's correlation. Results: In the hypertension group, body mass index (BMI), hsCRP, NLR, SII, SIRI, NMR, time to HIV diagnosis, ART duration, CD4+ and CD8+ cell counts, and CD4+/CD8+ ratio, the ratio of HIV-RNA < 100 copies/mL were all higher than those in the non-hypertension group, while the PNR was lower than that in the non-hypertension group. ART duration, CD4+ cell counts, HIV-RNA < 100 copies/mL, hsCRP, SIRI, and NMR were positively associated with hypertensive risk in PLWH. CD8+ cell counts and CD4+/CD8+ ratio was negatively associated with hypertensive risk in PLWH. SIRI was negatively correlated with CD4+ cell counts and CD8+ cell counts, but positively correlated with CD4+/CD8+ ratio. Conclusions: We identified positive associations between inflammation markers hsCRP, SIRI, NMR and hypertensive risk in PLWH. Alleviating inflammation may help control or delay the occurrence of hypertension in PLWH.

Mediation of the association between stigma and HIV status and fertility intention by fertility desire among heterosexual couples living with HIV in Kunming, China.

OBJECTIVES: This study aimed to assess the influences of stigma and HIV status on reproductive intention among heterosexual couples living with HIV in China. METHODS: A cross-sectional study was conducted in Kunming, China among 315 HIV-positive individuals and their spouses (n = 315 couples). An interview questionnaire was used to collect data on intention, desire, HIV Stigma Scale items, and HIV status. Dyadic fertility intention was examined using the actor-partner interdependence mediation model, based on the Traits-Desires-Intentions-Behavior framework. RESULTS: The husbands' or wives' internalized stigma had significant negative effects on their own fertility desire (ß = -0.149, p<0.05 and ß = -0.238, p<0.01, respectively). HIV-positive status of the husbands was weakly linked to their own fertility intention (ß = -0.181, p<0.05). Husbands' perceived provider stigma was associated with their own and their wives' fertility intention via the mediating effect of their fertility desire (ß = -0.374, p<0.001 and ß = -0.203, p<0.01, respectively). The cumulative influence of their reproductive desire mediated the husband's perceived provider stigma and the wife's internalized stigma on their fertility intention. CONCLUSIONS: Stigma and HIV status were associated with fertility intention among couples living with HIV, mediated by fertility desire. The high intra-couple correlation suggested that counseling should be conducted when both spouses are present together with extensive discussions on concerns regarding HIV-related stigma, potential discrepancies between each partner's fertility desire and intention, and the influence of one partner on the other.

Effects of HIV-related worries on fertility motivation moderated by living children among couples living with HIV: A dyadic analysis.

Introduction: HIV-related worries are a major barrier to achieving fertility goals for couples living with HIV (CLWH). We examined the moderating role of living children in the association between HIV-related worries and fertility motivation in CLWH including happiness, well-being, identity, and continuity. Methods: The data of 322 reproductive-aged CLWH were collected for this cross-sectional study from a referral antiretroviral therapy clinic in Kunming, China between October and December 2020. Intra- and interpersonal mechanisms of association between HIV-related worries and fertility motivation moderated by the number of living children in husband-wife dyads were analyzed by the actor-partner interdependence moderation model. Results: The high-level HIV-related worries of the wives and husbands were associated with the spouses' fertility motivation. Having at least one child helped to ameliorate the negative association between one's own HIV-related worries and fertility motivation. However, there was no evidence of such moderation in the spouse. Conclusion: Whether the CLWH has at least one living child should be taken into account in counseling. Childless families should be counseled on HIV-related worries as those worries have a greater negative effect on fertility motivation than couples who have a child.

Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users.

Background: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown. Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS). Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log2(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8+ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR. Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.

Factors Affecting Fertility Intention Among People Living with HIV in Kunming, China.

Background: Survival and quality of life of people living with HIV (PLWH) have been improving. Understanding fertility intention among PLWH is critical in helping them accomplish their pregnancy goals while significantly lowering the risk of HIV transmission. The purpose of this study was to identify factors based on the theory of planned behavior (TPB) that may explain fertility intention among PLWH. Methods: A survey was conducted in face-to-face interviews based on TPB, and the latent variables were devised and tested for their potential influences on fertility intentions in 487 reproductive-aged PLWH at antiretroviral treatment clinics in Kunming, China. Analysis was mainly based on the structural equation model. Results: About 38.4% of the respondents answered that they were likely to have a/another child in the next three years. Our hypothesized factors could explain 53.7% of the total variance of fertility intention. The 20- to 35-year-old group had a higher fertility intention. Perceived partner expectations toward fertility were the strongest predictors of fertility intention followed by beliefs in the support of the two-child policy. In contrast, the three components of attitudes, subjective norm, and perceived behavioral control did not influence fertility intention. Conclusion: In this HIV endemic area of China, fertility intended by PLWH is a matter of the couple that is also influenced by the national population fertility policy.

Epidemiology of concurrent extrapulmonary tuberculosis in inpatients with extrapulmonary tuberculosis lesions in China: a large-scale observational multi-centre investigation.

AIMS: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. METHODS: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. RESULTS: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). CONCLUSIONS: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

Measuring the uptake of continuous care among people living with HIV receiving antiretroviral therapy and social determinants of the uptake of continuous care in the southwest of China: a cross-sectional study.

BACKGROUND: Continuous care is essential for people living with HIV. This study aimed to measure continuous care uptake and investigate the association between higher uptake of continuous care and behavioral and social factors, including HIV-acquisition risk and socioeconomic characteristics. METHODS: A hospital-based cross-sectional study was conducted from April to November 2019 in an HIV treatment center of a specialized hospital in Kunming city, China. Fourteen service indicators were used to calculate composite care scores, which were classified into three levels (low, middle, and high), using principal component analysis. The Behavioral Model for Vulnerable Populations was employed to examine predisposing, enabling, and need factors associated with composite care scores among people living with HIV. RESULTS: A total of 702 participants living with HIV aged ≥ 18 years (median age: 41.0 years, 69.4% male) who had been on ART for 1-5 years were recruited. Based on ordinal logistic regression modeling, predisposing factors: being employed (adjusted odds ratio (AOR): 1.54, 95% confidence interval (CI): 1.13-2.11), heterosexuals (AOR: 1.58, 95% CI: 1.11-2.25) and men who have sex with men (AOR: 2.05, 95% CI: 1.39-3.02) and enabling factors: Urban Employee Basic Medical Insurance (AOR: 1.90, 95% CI: 1.03-3.54), middle socioeconomic status (SES) (AOR: 1.42, 95% CI: 1.01-2.01), were positively associated with the higher level of continuous care uptake, compared to the unemployed, people who inject drugs, those with no medical insurance and low SES, respectively. CONCLUSION: There were large differences in continuous care uptake among people living with HIV. HIV-acquisition risk categories and socioeconomic factors were significant determinants of uptake of continuous care. Our findings could inform the development of evidence-based strategies that promote equitable healthcare for all people living with HIV.

Measuring and explaining inequality of continuous care for people living with HIV receiving antiretroviral therapy in Kunming, China.

BACKGROUND: In the context of scaling up free antiretroviral therapy (ART), healthcare equality is essential for people living with HIV. We aimed to assess socioeconomic-related inequalities in uptake of continuous care for people living with HIV receiving ART, including retention in care in the last six months, routine toxicity monitoring, adequate immunological and virological monitoring, and uptake of mental health assessment in the last 12 months. We also determined the contributions of socioeconomic factors to the degree of inequalities. METHODS: A hospital-based cross-sectional survey was conducted among consecutive clients visiting an HIV treatment center in Kunming, China in 2019. Participants were 702 people living with HIV aged ≥18 years (median age: 41.0 years, 69.4% male) who had been on ART for 1-5 years. Socioeconomic-related inequality and its contributing factors were assessed by a normalized concentration index (CIn) with a decomposition approach. RESULTS: The uptake of mental health assessment was low (15%) but significantly higher among the rich (CIn 0.1337, 95% CI: 0.0140, 0.2534). Retention in care, toxicity, and immunological monitoring were over 80% but non-significant in favor of the rich (CIn: 0.0117, 0.0315, 0.0736, respectively). The uptake of adequate virological monitoring was 15% and higher among the poor (CIn = -0.0308). Socioeconomic status positively contributed to inequalities of all care indicators, with the highest contribution for mental health assessment (124.9%) and lowest for virological monitoring (2.7%). CONCLUSIONS: These findings suggest virological monitoring and mental health assessment be given more attention in long-term HIV care. Policies allocating need-oriented resources geared toward improving equality of continuous care should be developed.

Dynamic transcriptome landscape of Paragonimus proliferus developmental stages in the rat lungs.

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.

CD8+ T cells predicted the conversion of common covid-19 to severe.

To evaluate the predictive effect of T-lymphoid subsets on the conversion of common covid-19 to severe. The laboratory data were collected retrospectively from common covid-19 patients in the First People's Hospital of Zaoyang, Hubei Province, China and the Third People's Hospital of Kunming, Yunnan Province, China, between January 20, 2020 and March 15, 2020 and divided into training set and validation set. Univariate and multivariate logistic regression was performed to investigate the risk factors for the conversion of common covid-19 to severe in the training set, the prediction model was established and verified externally in the validation set. 60 (14.71%) of 408 patients with common covid-19 became severe in 6-10 days after diagnosis. Univariate and multiple logistic regression analysis revealed that lactate (P = 0.042, OR = 1097.983, 95% CI 1.303, 924,798.262) and CD8+ T cells (P = 0.010, OR = 0.903, 95% CI 0.835, 0.975) were independent risk factors for general type patients to turn to severe type. The area under ROC curve of lactate and CD8+ T cells was 0.754 (0.581, 0.928) and 0.842 (0.713, 0.970), respectively. The actual observation value was highly consistent with the prediction model value in curve fitting. The established prediction model was verified in 78 COVID-19 patients in the verification set, the area under the ROC curve was 0.906 (0.861, 0.981), and the calibration curve was consistent. CD8+ T cells, as an independent risk factor, could predict the transition from common covid-19 to severe.

The Protective Action of Piperlongumine Against Mycobacterial Pulmonary Tuberculosis in Its Mitigation of Inflammation and Macrophage Infiltration in Male BALB/c Mice.

INTRODUCTION: Piperlongumine (PL) is a bioactive alkaloid and medicinal compound of piperamide isolated from the long pepper (Piper longum Linn). It has demonstrated bactericidal action against Mycobacterium tuberculosis (MTB), the cause of pulmonary tuberculosis; nevertheless, immunomodulatory activity had not been identified for it in MTB-triggered granulomatous inflammation. This study investigated if piperlongumine could inhibit such inflammation. MATERIAL AND METHODS: Mycobacterium tuberculosis strain H37Rv was subjected to a broth microdilution assay. Piperlongumine at 5, 15, and 25 µg/mL, 0.2% dimethyl sulphoxide as control or 4 µM of dexamethasone were tested in vitro on MH-S murine alveolar macrophages. BALB/c mice were orally administered PL at 50, 100 and 150 mg/kg b.w. after trehalose-6,6-dimycolate (TDM) stimulation. Chemokine and cytokine concentrations were determined in lung supernatants. Flow cytometry and Western blot analysis were performed to determine phosphorylated spleen tyrosine kinase (Syk), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. RESULTS: Piperlongumine inhibited inflammatory mediators and adherence of lymphocyte function-associated antigen 1 to MH-S cells following TDM activation. It also improved macrophage clearance of MTB. In TDM-stimulated MH-S cells, PL significantly influenced the macrophage inducible Ca2+-dependent lectin receptor (Mincle)-Syk-ERK signalling pathway. Oral dosing of PL effectively suppressed the development of pulmonary granulomas and inflammatory reactions in the TDM-elicited mouse granuloma model. CONCLUSION: PL as an inhibitor of MTB-triggered granulomatous inflammation may be an effective complementary treatment for mycobacterial infection.

New triterpenes from Cimicifuga yunnanensis down-regulating the mRNA expression of CD147, MMP-2, and MMP-9.

Eleven new 9,19-cycloartane triterpenes (1-9, 11-12) and one undescribed lanostane-type aglycone (10) were identified from the aerial parts of Cimicifuga yunnanensis. The new structures were elucidated by analysis of spectroscopic data. Compounds 3-5, 7-9, and 11, without obvious cytotoxicity at 50 µM, were evaluated for inhibiting the mRNA expressions of atherosclerosis-related factors of CD147 (extracellular matrix metalloproteinase inducer, EMMPRIN), matrix metalloproteinase 2 (MMP-2) and MMP-9 in phorbol-12-myristate-13-acetate (PMA) induced Human monocytic THP-1 cells by using a quantitative real-time PCR method (q-PCR). Among them, aglycones 7 and 8 showed potent activities, whereas all tested glycosides were inactive. Compounds 7 and 8 suppressed the mRNA expression of CD147 in a dose-dependent manner, with an IC50 value of 3.38 ± 0.27 µM and 8.25 ± 0.33 µM, respectively. Besides, 7 dose-related down-regulated the mRNA expression of MMP-2, and MMP-9, having an IC50 value of 6.32 ± 0.31 µM and 11.57 ± 0.23 µM, respectively. Meanwhile, 8 at 10 µM reduced the mRNA expression of MMP-2 and MMP-9 by 35% and 25%, respectively. Significantly, the migration ability of the induced THP-1 cells was potently and dose-dependently inhibited by 7, with an IC50 value of 5.87 ± 0.27 µM.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

Effects of Short-Term Low-Dose Glucocorticoids for Patients with Mild COVID-19.

OBJECTIVES: To evaluate the role of short-term low-dose glucocorticoids in mild COVID-19 patients. METHODS: We conducted a retrospective, cross-sectional, single-center study in Kunming, China. A total of 33 mild COVID-19 cases were divided into two treatment groups (with and without glucocorticoids, methylprednisolone, were used in this setting), and the absolute value of peripheral blood lymphocyte count; CD3+, CD4+, and CD8+ T cell counts; and the time to achieve negative transformation of a nucleic acid pharyngeal swab were recorded. Peripheral blood lymphocyte and T cell counts were compared between the treatment group and 25 healthy individuals. At the point of time when there was a 50% accumulation conversion rate (positive to negative nucleic acid on pharyngeal swab), and the nucleic acid turned negative in half of the patients in two groups, the peripheral blood lymphocyte and T cell counts were compared between treatment groups. RESULTS: The mean cumulative time for the 50% negative conversion rate of the nucleic acid in the pharyngeal swab was 17.7 ± 5.1 days and 13.9 ± 5.4 days in the glucocorticoid group and the nonglucocorticoid group, respectively. The absolute peripheral blood lymphocyte count and the T cell subset count in the glucocorticoid group were lower than those in the nonglucocorticoid group. When the nucleic acid turned negative in half of the patients, the absolute value of peripheral blood lymphocyte count and CD4+ T cells of the glucocorticoid group and the nonglucocorticoid group was not significantly different; the CD3+ and CD8+ T cells in the glucocorticoid group were lower than those in the nonglucocorticoid group. The absolute peripheral blood lymphocyte count, CD3+ T cells, and CD4+ T cells in the glucocorticoid group were lower than those of the healthy group during the whole disease period, and CD8+ T cells returned to normal at 19-21 days of the disease period. There was no significant difference between the nonglucocorticoid group and the healthy group for absolute peripheral blood lymphocyte and CD8+ T cells; moreover, CD3+ T cells and CD4+ T cells were lower in the nonglucocorticoid group than those in the healthy group from the day of admission to the 18th day and returned to normal at the period of 19-21 days. The absolute peripheral lymphocyte count (P = 0.048, effect size d = 0.727) and T cell subset count (CD3: P = 0.042, effect size d = 0.655; CD4: P < 0.01, effect size d = 0.599; and CD8: P = 0.034, effect size d = 0.550) in the nonglucocorticoid group were higher than those in the glucocorticoid group, and the difference between the groups was statistically significant. CONCLUSIONS: This study found that the use of short-term, low-dose glucocorticoids does not negatively influence the clinical outcome, without affecting the final clearance of viral nucleic acid in mild COVID-19 patients.

Adherence to Hepatocellular Carcinoma Surveillance and Perceived Barriers Among High-Risk Chronic Liver Disease Patients in Yunnan, China.

BACKGROUND: Data concerning adherence to hepatocellular carcinoma (HCC) surveillance among chronic liver disease (CLD) patients at high risk of developing HCC in China are limited. We aimed to examine the relationship between HCC-related knowledge dimensions and adherence to HCC surveillance procedures among chronic liver disease patients at high risk of developing HCC and to identify potential barriers. METHODS: A total of 380 patients with chronic liver disease at high risk of developing HCC were recruited between May and August 2018 to complete a survey during the first week of their first hospitalization at the Third People's Hospital of Kunming in China. We followed up each patient up to 7 months by telephone to confirm whether the patient returned to complete investigations for HCC surveillance. Patient's socio-demographic characteristics, HCC-related knowledge, and perceived barriers to HCC surveillance were measured using a structured questionnaire during their hospitalization. Factor analysis was performed on the knowledge questions to reduce the dimensions. Univariate and multivariate analyses were performed to examine the association between dimensions of HCC-related knowledge and patients' adherence to HCC surveillance. RESULTS: A total of 327 eligible patients had been successfully contacted in the follow-up phase. Only a quarter of patients completed HCC surveillance within 7 months after their first admission to hospital. High costs and perceived poor test efficacy were the two major barriers for HCC surveillance. Three common factors were derived from the factor analysis of HCC-related knowledge, namely, "Surveillance", "Lifestyle", and 'Prognosis'. Knowledge of HCC surveillance and lifestyle but not prognosis had an influence on adherence to HCC surveillance. Patients with better surveillance and lifestyle knowledge domain had better adherence to HCC surveillance. CONCLUSION: Adherence to HCC surveillance procedures is low in the study area. Closing the gap in HCC-related knowledge, particularly regarding surveillance and lifestyle, may help to increase adherence rates.

The epidemiology of extrapulmonary tuberculosis in China: A large-scale multi-center observational study.

Tuberculosis (TB) remains a serious global public health problem in the present. TB also affects other sites (extrapulmonary tuberculosis, EPTB), and accounts for a significant proportion of tuberculosis cases worldwide. In order to comprehensively understand epidemiology of EBTB in China, and improve early diagnosis and treatment, we conducted a large-scale multi-center observational study to assess the demographic data and the prevalence of common EPTB inpatients, and further evaluate the prevalence of EPTB concurrent with Pulmonary tuberculosis (PTB) and the associations between multiple EPTB types and gender-age group in China. All consecutive age≥15yr inpatients with a confirmed diagnosis of EPTB during the period from January 2011 to December 2017 were included in the study. The descriptive statistical analysis included median and quartile measurements for continuous variables, and frequencies and proportions with 95% confidence intervals (CIs) for categorical variables. Multinomial logistic regression analysis was used to compare the association of multiple EPTB types between age group and gender. The results showed that the proportion of 15-24 years and 25-34 years in EPTB inpatients were the most and the ratio of male: female was 1.51. Approximately 70% of EPTB inpatients were concurrent with PTB or other types of EPTB. The most common of EPTB was tuberculous pleurisy (50.15%), followed by bronchial tuberculosis (14.96%), tuberculous lymphadenitis of the neck (7.24%), tuberculous meningitis (7.23%), etc. It was found that many EPTB inpatients concurrent with PTB. The highest prevalence of EPTB concurrent with PTB was pharyngeal/laryngeal tuberculosis (91.31%), followed by bronchial tuberculosis (89.52%), tuberculosis of hilar lymph nodes (79.52%), tuberculosis of mediastinal lymph nodes (79.13%), intestinal tuberculosis (72.04%), tuberculous pleurisy (65.31%) and tuberculous meningitis (62.64%), etc. The results from EPTB concurrent with PTB suggested that females EPTB inpatients were less likely to be at higher risk of concurrent PTB (aOR = 0.819, 95%CI:0.803-0.835) after adjusted by age. As age increasing, the trend risk of concurrent PTB decreased (aOR = 0.994, 95%CI: 0.989-0.999) after adjusted by gender. Our study demonstrated that the common EPTB were tuberculous pleurisy, bronchial tuberculosis, tuberculous lymphadenitis of the neck, tuberculous meningitis, etc. A majority of patients with pharyngeal/laryngeal tuberculosis, bronchial tuberculosis, tuberculosis of hilar/mediastinal lymph nodes, intestinal tuberculosis, tuberculous pleurisy, tuberculous meningitis, etc. were concurrent with PTB. Female EPTB inpatients were less likely to be at higher risk of concurrent PTB, and as age increasing, the trend risk of concurrent PTB decreased. The clinicians should be alert to the presence of concurrent tuberculosis in EPTB, and all suspected cases of EPTB should be assessed for concomitant PTB to determine whether the case is infectious and to help for early diagnosis and treatment.