Trends in the prevalence of social isolation among middle and older adults in China from 2011 to 2018: the China Health and Retirement Longitudinal Study.

BACKGROUND: Epidemiological studies have shown that social isolation, which is prevalent in older adults, is associated with a range of adverse health outcomes, but the prevalence of and trends in regard to social isolation remain ambiguous in China. The aim of this study was to elucidate the trends regarding the prevalence of social isolation among middle-aged and older adults in China from 2011 to 2018 and to further identify associated risk factors. METHODS: A repeated cross-sectional study, The data were derived from panel sample data of four waves conducted from May 2011 to August 2018 in the nationally representative China Health and Retirement Longitudinal Study (CHARLS) using multistage probability sampling. Social isolation was ascertained by the five item Steptoe Social Isolation Index. The potential covariates were demographic characteristics, lifestyle factors, and health status. Linear-by-linear association was used to assess the trends in regard to social isolation over time under the influence of the potential covariates. Linear-by-linear association and an age-period-cohort analysis were used to explore the trends, and two-level (time, individual) generalized estimating equation models (GEE) linked multivariate binary logistic regression were performed to identify risk factors. RESULTS: A high prevalence of social isolation and a moderate upward trend from 2013 to 2018 were observed among a U-shaped trend prevalence of social isolation from 2011 to 2018 across China, with rates of 38.09% (95% CI = 36.73-39.45) in 2011, 33.66% (32.32-35.00) in 2013, 39.13% (37.59-40.67) in 2015, and 39.95% (38.59-41.31) in 2018 (p < 0.001). The prevalence of social isolation increased with age and educational attainment. Females had a higher prevalence than males. The prevalence of social isolation was found to be significantly lower in pensioners than in non-pensioners between 2011 and 2018 (p < 0.001). The prevalence of social isolation was 38.9%, 34.9%, 38.5%, and 44.08% about three times higher among those who doid not use the Internet and 13.44%, 11.64%, 12.93%, and 16.73% than among those who doid in 2011, 2013, 2015 and 2018 respectively. The participants with short (0-5 h) and long sleep (9 or more hours), and poor self-rated health had a higher prevalence of social isolation than the others. Older age, lower educational attainment, living in a rural region, lack of medical insurance or pension, lack of internet use and poor health were risk factors (p < 0.05). CONCLUSIONS: We found a U-shaped prevalence of social isolation trends from 2011 to 2018 and revealed increasing trends from 2013 to 2018 among middle-aged and older adults in China. The findings of the study highlight the urgent need for interventions to reduce social isolation including improving sleep quality and internet skills. Disadvantaged groups in terms of age, economic status, and health status should be the focus of such interventions, especially in the era of COVID-19.

IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L.

Little is known about how the immune system impacts human colorectal cancer invasiveness and stemness. Here we detected interleukin-22 (IL-22) in patient colorectal cancer tissues that was produced predominantly by CD4(+) T cells. In a mouse model, migration of these cells into the colon cancer microenvironment required the chemokine receptor CCR6 and its ligand CCL20. IL-22 acted on cancer cells to promote activation of the transcription factor STAT3 and expression of the histone 3 lysine 79 (H3K79) methytransferase DOT1L. The DOT1L complex induced the core stem cell genes NANOG, SOX2, and Pou5F1, resulting in increased cancer stemness and tumorigenic potential. Furthermore, high DOT1L expression and H3K79me2 in colorectal cancer tissues was a predictor of poor patient survival. Thus, IL-22(+) cells promote colon cancer stemness via regulation of stemness genes that negatively affects patient outcome. Efforts to target this network might be a strategy in treating colorectal cancer patients.

Creatine chemical exchange saturation transfer (CEST) CMR imaging reveals myocardial early involvement in idiopathic inflammatory myopathy at 3T: feasibility and initial experience.

OBJECTIVES: To measure creatine distribution in idiopathic inflammatory myopathy (IIM) patients' myocardial segments and investigate whether cardiovascular magnetic resonance (CMR) chemical exchange saturation transfer (CEST) creatine mapping can detect subclinical myocardial changes, CEST's ability was further compared with other conventional CMR mapping sequences. METHODS: Forty IIM patients (53.5 ± 10.5 years, 26 males) and eight healthy controls (35.4 ± 6 years, 5 males) underwent CMR scans on a 3.0-T MR scanner. Patients with IIM were further classified into two subgroups according to cardiac troponin T (cTn-T) values: the elevated cTn-T subgroup (n = 14) and the normal cTn-T subgroup (n = 26). Cine imaging, T2 SPAIR, LGE imaging, T1 mapping, T2 mapping, and Cr (creatine) CEST were performed. RESULTS: Cr mapping showed significantly reduced creatine in IIM patients among global myocardium (IIM: 0.109 ± 0.063, controls: 0.121 ± 0.021, p < 0.05), and decreased creatine signals were detected in all 16 cardiac segments (p < 0.05). Patients also had significantly prolonged native T1 and decreased enhanced T1 values in each cardiac segment (p < 0.05). There was no significant difference of LVEF and T2 values between IIM patients and controls. Between the two subgroups, elevated cTn-T was linked with creatine and extracellular volume fraction (ECV) values, providing a global average creatine signal of 0.107 vs 0.112 (p < 0.05) and 24.7 vs 32.4 (p < 0.05). CONCLUSION: Creatine CEST mapping can detect early-stage heart involvement with negative LGE findings in IIM. Compared with T1 mapping, CEST provides increased sensitivity to ECV measurement, making it significantly better than T1, and a promising CMR sequence for screening subclinical myocardial damage. KEY POINTS: • IIM patients with potential or ongoing heart involvement, elevated ECV, and reduced Cr CEST values could provide valuable information. • ECV and Cr CEST values were closely related to elevated cTn-T.

Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricaemia: a randomized controlled phase II study.

OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. RESULTS: 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS: The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.

Comparing the reliability and validity of the SF-36 and SF-12 in measuring quality of life among adolescents in China: a large sample cross-sectional study.

OBJECTIVE: We compare the reliability and validity of the Short Form 36 (version 1, SF-36) and the Short Form 12 (version 1, SF-12) in adolescence, the period of life when a child develops into an adult, i.e., the period from puberty to maturity terminating legally at the age of majority (10-19 years), thus supplying evidence for the selection of instruments measuring the quality of life (QOL) and decision-making processes of adolescents in China. METHODS: Stratified cluster random sampling was adopted according to geographical location, and the SF-36 was administered to assess QOL. The Pearson correlation coefficient was used to show correlation. Cronbach's alpha and construct reliability (CR) were used to evaluate the reliability of SF-36 and SF-12, while criterion validity and average variance extracted (AVE, convergence validity) were used to evaluate validity. Confirmatory factor analysis was used to calculate the load factors for the items of the SF-36 and SF-12, then to obtain the CR and AVE. The Semejima grade response model (logistic two-parameter module) in item response theory was used to estimate item discrimination, item difficulty, and item average information for the items of the SF-36 and SF-12. RESULTS: 19,428 samples were included in the study. The mean age of respondents was 14.78 years (SD = 1.77). Reliability of each domain of the SF-36 was better than for the corresponding domain of the SF-12. The domains of PF, RP, BP, and GH in SF-36 had good construct reliability (CR > 0.6). The criterion validities of some domains of the SF-36 were a little higher in some corresponding dimensions of the SF-12, except for PCS. The convergence validities of the SF-12 were higher than the SF-36 in PF, RP, BP, and PCS. The items of BP, SF, RP, and VT in the SF-12 had acceptable discrimination of items that were higher than in the SF-36. The items' average amounts of information on BP, VT, SF, RE, and MH in the SF-36 and SF-12 were poor. CONCLUSION: Two component (PCS and MCS) measurements of the SF-12 appeared to perform at least as well as the SF-36 in cross-sectional settings in adolescence, but the reliability and validity of the 8 domains of the SF-36 were better than those of the SF-12. Some domains, for instance SF and BP, were not suitable for adolescents or need to be studied further.

Factors influencing utilization of primary health care by elderly internal migrants in China: the role of social contacts.

BACKGROUND: Utilization of primary health care is an important aspect of elderly internal migrants' access to screening and preventive services in China. It has been evident that social contacts, such as community engagement, social mobilization, and the ability to communicate were related to health service delivery, but little has been done to explore the relationship between social contacts and utilization of primary health care for this group. This study aimed to explore the factors influencing utilization of primary health care from the perspective of social contacts among elderly internal migrants in China. METHODS: This was a cross-sectional study including 1544 elderly internal migrants in eight cities. Whether these indivdiuals had chosen to participate in the free health checkup organized in the previous year was adopted as an indicator of the utilization of primary health care. The number of local friends and amount of exercise time per day were measured as a proxy for social contacts. Multivariate binary logistic regression was used to investigate the association of social contacts with the likelihood of using primary health care. RESULTS: 55.6% of the respondents were men, and the mean age was 66.34 years (SD, 5.94). 88.6% had received an education of high school or below. 12.9% had no local friends. 5.2% did not exercise. Just 33.1% had participated in a free medical check-up. Social contacts, age, and medical insurance were associated with more use of primary health care among elderly internal migrants in China. CONCLUSION: The role of the community in promoting the use of primary health care should be expanded, such as creating community-based campaigns specifically targeting elderly internal migrants or designing social or sports activities tailored to increase the opportunity for contact between local elders and their internal migrant peers.

Multiparameter diffusion-weighted imaging for characterizing pathological patterns in lupus nephritis patients: A preliminary study.

BACKGROUND: Microstructural changes of lupus nephritis (LN) kidney such as inflammatory cell infiltration or fibrosis could influence water molecular movement or diffusion, which indicates that diffusion-weighted imaging (DWI) may become a valuable tool in evaluation of this disease. PURPOSE: To explore whether multiparameter diffusion-weighted imaging (mDWI) could contribute to characterize pathological patterns in LN patients. STUDY TYPE: Retrospective. POPULATION: Twenty-two patients with LN. FIELD STRENGTH/SEQUENCE: Multi-b value DWI was performed with a 3.0 T scanner. ASSESSMENT: Apparent diffusion coefficient (ADC)m , perfusion-related diffusion coefficient (Df ), molecular diffusion coefficient (Ds ), perfusion fraction (f), ADCs , α, ADCk , and mean kurtosis (MK) were calculated by monoexponential, biexponential, stretched-exponential, and kurtosis models fits, respectively. STATISTICAL TESTS: Independent sample t-test, Pearson analysis and receiver operating characteristic (ROC). RESULTS: In the whole group, the activity index (AI) correlated significantly with alpha values in the medulla (rho = -0.54, P = 0.03). The chronicity index (CI) correlated significantly with Ds values in the medulla (rho = -0.61, P = 0.02). No significant association was found between any other diffusion parameter and histologic grade with all P > 0.05. For differentiating proliferative LN (Class III or IV) from Class V, the area under the ROC curve (AUC) of alpha in the medulla was 0.833 (P = 0.023). DATA CONCLUSION: mDWI might be used for the characterization of pathological patterns in LN patients. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1075-1084.

The Novel Transcriptional Regulator LmbU Promotes Lincomycin Biosynthesis through Regulating Expression of Its Target Genes in Streptomyces lincolnensis.

Lincomycin A is a clinically important antimicrobial agent produced by Streptomyces lincolnensis In this study, a new regulator designated LmbU (GenBank accession no. ABX00623.1) was identified and characterized to regulate lincomycin biosynthesis in S. lincolnensis wild-type strain NRRL 2936. Both inactivation and overexpression of lmbU resulted in significant influences on lincomycin production. Transcriptional analysis and in vivo neomycin resistance (Neor) reporter assays demonstrated that LmbU activates expression of the lmbA, lmbC, lmbJ, and lmbW genes and represses expression of the lmbK and lmbU genes. Electrophoretic mobility shift assays (EMSAs) demonstrated that LmbU can bind to the regions upstream of the lmbA and lmbW genes through the consensus and palindromic sequence 5'-CGCCGGCG-3'. However, LmbU cannot bind to the regions upstream of the lmbC, lmbJ, lmbK, and lmbU genes as they lack this motif. These data indicate a complex transcriptional regulatory mechanism of LmbU. LmbU homologues are present in the biosynthetic gene clusters of secondary metabolites of many other actinomycetes. Furthermore, the LmbU homologue from Saccharopolyspora erythraea (GenBank accession no. WP_009944629.1) also binds to the regions upstream of lmbA and lmbW, which suggests widespread activity for this regulator. LmbU homologues have no significant structural similarities to other known cluster-situated regulators (CSRs), which indicates that they belong to a new family of regulatory proteins. In conclusion, the present report identifies LmbU as a novel transcriptional regulator and provides new insights into regulation of lincomycin biosynthesis in S. lincolnensisIMPORTANCE Although lincomycin biosynthesis has been extensively studied, its regulatory mechanism remains elusive. Here, a novel regulator, LmbU, which regulates transcription of its target genes in the lincomycin biosynthetic gene cluster (lmb gene cluster) and therefore promotes lincomycin biosynthesis, was identified in S. lincolnensis strain NRRL 2936. Importantly, we show that this new regulatory element is relatively widespread across diverse actinomycetes species. In addition, our findings provide a new strategy for improvement of yield of lincomycin through manipulation of LmbU, and this approach could also be evaluated in other secondary metabolite gene clusters containing this regulatory protein.

The social income inequality, social integration and health status of internal migrants in China.

BACKGROUND: To examine the interaction between social income inequality, social integration, and health status among internal migrants (IMs) who migrate between regions in China. METHODS: We used the data from the 2014 Internal Migrant Dynamic Monitoring Survey in China, which sampled 15,999 IMs in eight cities in China. The Gini coefficient at the city level was calculated to measure social income inequality and was categorized into low (0.2 < Gini <= 0.3), medium (0.3 < Gini <= 0.4), high (0.4 < x < = 0.5), and very high (Gini >0.5). Health status was measured based upon self-reported health, subjective well-being, and perceptions of stress and mental health. Social integration was measured from four perspectives (acculturation and integration willingness, social insurance, economy, social communication). Linear mixed models were used to examine the interaction effects between health statuses, social integration, and the Gini coefficient. RESULTS: Factors of social integration, such as economic integration and acculturation and integration willingness, were significantly related to health. Social income inequality had a negative relationship with the health status of IMs. For example, IMs in one city, Qingdao, with a medium income inequality level (Gini = 0.329), had the best health statuses and better social integration. On the other hand, IMs in another city, Shenzhen, who had a large income inequality (Gini = 0.447) were worst in health statues and had worse social integration. CONCLUSION: Policies or programs targeting IMs should support integration willingness, promote a sense of belonging, and improve economic equality. In the meantime, social activities to facilitate employment and create social trust should also be promoted. At the societal level, structural and policy changes are necessary to promote income equity to promote IMs' general health status.

A positive feedback loop between STAT3 and cyclooxygenase-2 gene may contribute to Helicobacter pylori-associated human gastric tumorigenesis.

Persistent infection with Helicobacter pylori (H. pylori) contributes to gastric diseases including chronic gastritis and gastric cancer. However, the pathogenesis of this carcinogenic bacterium has not been completely elucidated. Here, we report that H. pylori rapidly triggers STAT3 signaling and induces STAT3-dependent COX-2 expression both in vitro and in vivo. STAT3 upregulates COX-2 by binding to and increasing the activity of COX-2 promoter. COX-2 in turn regulates IL-6/STAT3 signaling under basal conditions and during H. pylori infection. These findings suggest that a positive feedback loop between STAT3 and COX-2 exists in the basal condition and H. pylori infectious condition. Immunohistochemical staining revealed that H. pylori-positive gastritis tissues exhibited markedly higher levels of pSTAT3(Tyr705) than H. pylori-negative ones. High pSTAT3(Tyr705) levels are correlated with intestinal metaplasia and dysplasia, suggesting pSTAT3(Tyr705) may be useful in the early detection of gastric tumorigenesis. Additionally, a strong positive correlation between STAT3/pSTAT3(Tyr705) levels and COX-2 expression was identified in gastritis and gastric cancer tissues. Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer

Role of STAT3 and vitamin D receptor in EZH2-mediated invasion of human colorectal cancer.

The polycomb group protein enhancer of zeste homologue 2 (EZH2), which has histone methyltransferase (HMT) activity, is overexpressed in malignant tumours. However, the role of EZH2 in colorectal cancer (CRC) invasion is little known. Here we investigated the clinical significance, biological effects, and mechanisms of EZH2 signalling. Knockdown of EZH2 significantly reduced cell invasion and secretion of matrix metalloproteinases 2/9 (MMP2/9) in in vitro studies. Knockdown of EZH2 dramatically increased overall survival and decreased metastasis of lung in in vivo studies. Conversely, overexpression of EZH2 significantly increased lung metastasis and shortened overall survival when compared with control tumours. EZH2-induced CRC cell invasion may depend on down-regulation of vitamin D receptor (VDR), which is considered to be a marker of CRC invasion. EZH2 regulates the histone trimethylation of lysine 27 (H3K27me3) in the VDR promoter. Moreover, we found that STAT3 directly binds to the EZH2 promoter and regulates VDR down-regulation in CRC cells. Significant inverse correlations were observed between the expression of EZH2 and pSTAT3 and that of VDR in CRC tissues compared with normal tissue in patients. We show the role of EZH2 in CRC metastasis and identify VDR as a target gene of EZH2. EZH2 expression may be directly regulated by STAT3, and STAT3 may play an important role in EZH2-mediated VDR down-regulation in CRC. This pathway may provide potential targets in aggressive CRC.

Risk factors for mid- and long-term mortality in lung transplant recipients aged 70 years and older.

OBJECTIVES: With increased lung transplantation in those aged 70 and older, limited literature addresses risk factors affecting their survival. Our study aims to identify independent factors impacting mid- and long-term mortality in this elderly population. METHODS: This study analyzed lung transplant patients over 70 from May 2005 to December 2022 using United Network for Organ Sharing data. The 3- or 5-year cohort excluded multi-organ, secondary transplantation and loss to follow-up. Univariable Cox analysis was conducted to assess recipient, donor and transplant factors. Factors with a significance level of P < 0.2 were subsequently included in a multivariable Cox model to identify correlations with 3- and 5-year mortality in patients aged over 70. RESULTS: Multivariable analysis has identified key factors affecting 3- and 5-year mortality in elderly lung transplant patients over 70. Common notable factors include recipient total bilirubin, intensive care unit status at the time of transplantation, donor diabetes, Cytomegalovirus (CMV) mismatch and single lung transplantation. Additionally, Hispanic/Latino patients and ischaemia time of the transplant significantly impact the 3-year mortality, while recipient age, diabetes, nitric oxide use before transplantation and creatinine were identified as unique independent risk factors affecting the 5-year morality. CONCLUSIONS: The study identified several independent risk factors that impact the mid- and long-term survival of lung transplantation for individuals over 70 years. These findings can contribute to the optimization of lung transplant treatment strategies and perioperative management in elderly patients, thereby enhancing the survival rate of this age group.

Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition.

The progression of colorectal carcinoma (CRC) to invasive and metastatic disease may involve localized occurrences of epithelial-mesenchymal transition (EMT). However, mechanisms of the EMT process in CRC progression are not fully understood. We previously showed that knockdown of signal transducer and activator of transcription 3 (STAT3) up-regulated E-cadherin (a key component in EMT progression) in CRC. In this study, we examined the roles of STAT3 in CRC EMT and ZEB1, an EMT inducer, in STAT3-induced down-regulation of E-cadherin. Knockdown of STAT3 significantly increased E-cadherin and decreased N-cadherin and vimentin expressions in highly invasive LoVo CRC cells. Meanwhile, overexpression of STAT3 significantly reduced E-cadherin and enhanced N-cadherin and vimentin expressions in weakly invasive SW1116 CRC cells. Activation of STAT3 significantly increased CRC cell invasiveness and resistance to apoptosis. Knockdown of STAT3 dramatically enhanced chemosensitivity of CRC cells to fluorouracil. STAT3 regulated ZEB1 expression in CRC cells, and the STAT3-induced decrease in E-cadherin and cell invasion depended on activation of ZEB1 in CRC cells. Additionally, pSTAT3(Tyr-705) and ZEB1 expressions were significantly correlated with TNM (tumor, lymph node, and metastasis stages) (p < 0.01). In conclusion, STAT3 may directly mediate EMT progression and regulate ZEB1 expression in CRC. ZEB1 may participate in STAT3-induced cell invasion and E-cadherin down-regulation in CRC cells. The expressions of pSTAT3(Tyr-705) and ZEB1 may be positively associated with CRC metastasis. Our data may provide potential targets to prevent and/or treat CRC invasion and metastasis.

Identification of potential target genes of butyrate in dimethylhydrazine-induced colorectal cancer in mice.

The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The objective of this study was to identify potential target genes of butyrate in 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR. Data was further analyzed by KEGG, gene ontology (GO), and pathway studio software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and 90%, respectively (P < 0.05). There were 355 genes downregulated due to DMH treatment while upregulated by butyrate, and 475 genes upregulated by DMH while downregulated by butyrate. The results revealed that most of the tumor-related signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF pathway) were downregulated by butyrate. The GO terms related to cell differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and cell migration were significantly affected. The chemopreventive effects of butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms encompassing multiple pathways and GO terms are involved in the regulation of gene expression.

Clinical phenotypes and prognoses of microscopic polyangiitis based on kidney biopsies.

BACKGROUND: To classify the different clinical phenotypes and compare the distinct prognoses of microscopic polyangiitis (MPA). METHODS: A retrospective analysis of 436 patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) from 2015 to 2022 was conducted in our center, of which 90 patients were diagnosed with MPA and underwent renal biopsy. RESULTS: Among the 90 MPA patients, 63% were female, and the median age at onset was 63 years (25th-75th percentile: 58-68). The median follow-up time was 26 months (25th-75th percentile: 10-53). We identified four subtypes: renal impairment type (cluster 1, 39%), pure type (cluster 2, 22%), systemic inflammation type (cluster 3, 26%), and rapid progress type (cluster 4, 13%). Cluster 1, characterized by renal dysfunction at onset (80%), demonstrated poor prognoses with only 26% achieved complete remission (CR), 11% dying, and 19% developing renal failure. In contrast, patients in cluster 2, exclusively female, most had only kidney involvement showed the best prognoses with 55% achieving CR and none experiencing death or renal failure within 10 years. Cluster 3 mostly consisted of males; high fever and C-reactive protein levels were the primary characteristics. These cases exhibited moderate prognoses with 53% achieving CR, 9% dying, and 4% developing renal failure. Finally, patients in cluster 4, which was characterized by rapidly progressive glomerulonephritis, had the worst prognoses, with none achieving CR, 8% dying, and 75% developing renal failure despite aggressive treatment. CONCLUSIONS: MPA is classified into four subtypes with distinct clinical manifestations and prognoses.

Inhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathway.

Abnormalities in the JAK2/STAT3 pathway are involved in the pathogenesis of colorectal cancer (CRC), including apoptosis. However, the exact mechanism by which dysregulated JAK2/STAT3 signalling contributes to the apoptosis has not been clarified. To investigate the role of both JAK2 and STAT3 in the mechanism underlying CRC apoptosis, we inhibited JAK2 with AG490 and depleted STAT3 with a small interfering RNA. Our data showed that inhibition of JAK2/STAT3 signalling induced CRC cellular apoptosis via modulating the Bcl-2 gene family, promoting the loss of mitochondrial transmembrane potential (Δψm) and the increase of reactive oxygen species. In addition, our results demonstrated that the translocation of cytochrome c (Cyt c), caspase activation and cleavage of poly (ADP-ribose) polymerase (PARP) were present in apoptotic CRC cells after down-regulation of JAK2/STAT3 signalling. Moreover, inhibition of JAK2/STAT3 signalling suppressed CRC xenograft tumour growth. We found that JAK2/STAT3 target genes were decreased; meanwhile caspase cascade was activated in xenograft tumours. Our findings illustrated the biological significance of JAK2/STAT3 signalling in CRC apoptosis, and provided novel evidence that inhibition of JAK2/STAT3 induced apoptosis via the mitochondrial apoptotic pathway. Therefore, JAK2/STAT3 signalling may be a potential target for therapy of CRC.

STAT5 isoforms regulate colorectal cancer cell apoptosis via reduction of mitochondrial membrane potential and generation of reactive oxygen species.

Although the two isoforms of signal transducer and activator of transcription 5 (STAT5) protein, STAT5a and STAT5b, have 94% sequence identity, they are encoded by different genes. Previous studies have been unable to define clearly the roles of the STAT5 genes in colorectal cancer (CRC). To investigate the role of STAT5 isoforms in CRC oncogenesis, immunohistochemical staining was performed. Colorectal adenocarcinomas showed higher expression of STAT5a/5b than normal colonic mucosa (P < 0.05), and STAT5b expression was significantly higher than that of STAT5a in colorectal adenocarcinoma tissue (P < 0.05). Furthermore, STAT5b expression was significantly associated with TNM stage. To delineate the roles of STAT5a/5b in CRC carcinogenesis, we studied CRC cells depleted of each isoform by treating the cells with small interfering RNA. Both STAT5a and STAT5b were found to be involved in cell growth, cell cycle progression, and apoptosis of CRC cells, and exerted their effects via the regulation of downstream targets of the STAT genes. However, STAT5b influenced CRC cell apoptosis more than STAT5a (P < 0.05), reducing mitochondrial membrane potential and generating reactive oxygen species. In conclusion, both isoforms of STAT5 are involved in the growth and cell cycle progression of CRC cells, STAT5b could play a more important role than STAT5a in the clinicopathological characteristics of CRC and CRC cell apoptosis.

[Study on the changes of cardiac reserve function during normal vaginal delivery].

OBJECTIVE: To investigate the trend of cardiac reserve function during the normal labor. METHODS: Sixty-three cases were chosen randomly from hospitalized maternal women in the First Affiliated Hospital of Chongqing Medical University from 2010 June to December (six months). The digital technique of heart sound signal processing was used to analyze cardiac reserve function parameters including the heart rate (HR), the ratio of the amplitude of the first heart sound to the second heart sound (S1/S2) and the ratio of diastolic to systolic duration (D/S) of pregnant women. RESULTS: (1) Comparisons of cardiac reserve function between uterine contractions and relaxations during labor: 1) Latent phase of labor (cervix dilation < 3 cm):HR was (87.3 ± 14.0) beats/min in uterine contractions and (82.8 ± 12.5) beats/min in uterine relaxations, the ratio of D/S was 1.14 ± 0.27 in uterine contractions and 1.21 ± 0.22 in uterine relaxations, the comparisons of the above two were statistically significant, P < 0.05; But the ratio of S1/S2 was 2.19 ± 0.82 in uterine contractions and 2.28 ± 0.81 in uterine relaxations, the comparison was not statistically significant, P > 0.05. 2) During early active stage of labor (cervix dilation 3 - 6 cm):HR was (89.3 ± 15.4) beats/min in uterine contractions and (83.1 ± 13.5) beats/min in uterine relaxations, the ratio of D/S was 1.09 ± 0.30 in uterine contractions and 1.20 ± 0.27 in uterine relaxations, the comparisons of the above two were statistically significant, (P < 0.05); But the ratio of S1/S2 was 2.42 ± 1.08 in uterine contractions and 2.29 ± 0.83 in uterine relaxations, the comparison was not statistically significant (P > 0.05); 3) During late active stage of labor (cervix dilation 6 - 10 cm), HR was (95.4 ± 18.7) beats/min in uterine contractions and (86.2 ± 15.6) beats/min in uterine relaxations, the ratio of D/S was 1.01 ± 0.25 in uterine contractions and 1.18 ± 0.25 in uterine relaxations, the comparisons of the above two were statistically significant, (P < 0.05); But the ratio of S1/S2 was 2.61 ± 1.26 in uterine contractions and 2.67 ± 1.19 in uterine relaxations, the comparison was not statistically significant (P > 0.05). 4) The second stage of labor (cervical dilation ≥ 10 cm):HR was (109.4 ± 19.7) beats/min in uterine contractions and (93.5 ± 16.7) beats/min in uterine relaxations, the ratio of D/S was 0.89 ± 0.23 in uterine contractions and 1.14 ± 0.26 in uterine relaxations, the ratio of S1/S2 was 3.66 ± 1.37 in uterine contractions and (2.81 ± 1.07) in uterine relaxations, the comparisons of all were statistically significant (P < 0.05). (2) Comparison of cardiac reserve function in uterine relaxations of each stage of labor: 1) Maternal heart rate gradually increased from latent stage of labor to the second stage of labor, and decreased postpartum, the comparison was statistically significant (P < 0.05); 2) The ratio of S1/S2 of maternal gradually increased from latent stage of labor to the second stage of labor, and decreased postpartum, the comparison was statistically significant (P < 0.05); 3) The ratio of D/S gradually decreased from latency to the second stage of labor, and increased postpartum, the comparison was statistically significant (P < 0.05). (3) Comparison of cardiac reserve function in uterine contractions of each stage of labor: 1) Maternal heart rate gradually decreased from latent stage of labor to the second stage of labor, the comparison was statistically significant (P < 0.05); 2) The ratio of S1/S2 of maternal gradually increased from latent stage of labor to the second stage of labor, the comparison was statistically significant (P < 0.05); 3) The ratio of D/S gradually decreased from latency to the second stage of labor, the comparison was statistically significant (P < 0.05). CONCLUSIONS: The maternal cardiac reserve function decreased in uterine contractions than relaxation during labor; With the progress of labor, the maternal cardiac reserve function declined, especially in the second stage of labor, and recovered in postpartum stage.

Effect of living arrangements on cognitive function in Chinese elders: a longitudinal observational study.

OBJECTIVE: To examine how living arrangement as a social contextual factor can affect Chinese elders' cognitive function. SETTING AND PARTICIPANTS: Our sample consists of 2486 Chinese elders from two waves (2014 and 2018) of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) that was administered in 22 of China's 31 provinces using a multi-stage, disproportionate, purposive random sampling method. The CLHLS aims to better understand the determinants of healthy longevity in China and collects extensive data on a large population of fragile elders aged 80-112 in China. OUTCOME MEASURES: Cognitive function was measured by the Mini-Mental State Examination (MMSE). Living arrangement was divided into living in an institution, living alone and living with household members. Generalised linear regressions were carried out to examine the associations between baseline characteristics and cognitive function, while controlling age, gender and residential area. RESULTS: A total of 2486 participants were included in the study at baseline in 2014. Of these, 1162 (46.7%) were men and 1324 (53.3%) were women. The mean age at baseline was 75.07 (±8.31) years. The mean years of schooling were 2.86 (±3.68). The number (proportion) of the three living arrangements (lived in institutions, lived alone and lived with household members) were 93 (3.8%), 463 (18.6%) and 1930 (77.6%), respectively. Among all participants, cognitive function declined over time. Those who lived alone presented with the highest MMSE scores at baseline and showed the lowest decline after 4 years. Living arrangements had significant effects on decreasing cognitive function. CONCLUSION: Chinese elders living in institutions were most vulnerable to cognitive decline. Living alone was not a risk condition in itself for the elderly in terms of cognitive decline. In addition, the benefits of living with household members to support cognitive function were not found in our study.