Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis.

PURPOSE: Numerous clinical studies have explored sodium-glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients. METHODS: A comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials ( http://www. CLINICALTRIALS: gov ) were also searched. RESULTS: A total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: -253.36, - 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P < 0.00001), KCCQ overall summary (KCCQ-OS) score (WMD = 1.73, 95% CI [0.94, 2.52], P < 0.00001), and KCCQ total symptom (KCCQ-TS) score (WMD = 2.88, 95% CI [1.7, 4.06], P < 0.00001). Furthermore, the occurrence of KCCQ-CS and KCCQ-OS score increases ≥ 5 points had relative risks (RR) of 1.25 (95% CI [1.11, 1.42], P < 0.00001) and 1.15 (95% CI [1.09, 1.22], P < 0.00001), respectively. Overall, SGLT2 inhibitors increased the 6-minute walk distance by 23.98 m (95% CI [8.34, 39.62]; P = 0.003) compared to control/placebo from baseline. CONCLUSIONS: The SGLT2 inhibitors treatment offers an effective strategy for improving NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance in CHF with or without T2DM. These findings indicate that SGLT2i improve cardiac function and health status in CHF with or without T2DM, and provide valuable guidance for clinicians making treatment decisions for patients with CHF.

Racial/ethnic and nativity differences in adversity profiles among middle-aged and older adults.

OBJECTIVES: Focusing on the nexus of race/ethnicity and nativity, this study examined profiles of adversity and their mental health implications in five groups of middle-aged and older adults: native-born whites, native-born blacks, native-born Hispanics, foreign-born whites, and foreign-born Hispanics. METHODS: Data were from the 2018 psychosocial assessment of the HRS (N = 5,223). Latent class analysis (LCA) was employed to identify patterns of eleven adversity indicators and to compare the latent structures and class prevalence across the race/ethnicity and nativity groups. Regressions were used to examine the associations between adversity profiles and depression and life satisfaction, respectively. RESULTS: Four adversity profiles emerged: low adversity (59.84%), low human capital (15.27%), socially marginalized (15.26%), and neighborhood adversity (9.63%). Regardless of nativity status, white older adults were most likely to have the low adversity profile (74 ∼ 75%). In contrast, all the racial/ethnic minority groups were more likely to have the other three adversity profiles. The adversity experienced by racial/ethnic minorities was further cofounded by their immigration status. Overall, having low adversity was associated with the best mental health outcomes and socially marginalized had the poorest outcomes. Even with the low adversity profile, native-born blacks had significantly more depressive symptoms than native-born whites. CONCLUSION: Findings revealed heterogeneity in adversity profiles and their mental health implications in disadvantaged aging populations. Tailored programs are needed to address unique needs of different minority populations.

Immigration-Related Factors and Depression Help-Seeking Behaviors Among Older Chinese Americans.

OBJECTIVES: Asian Americans have the lowest mental health service utilization rate among all racial/ethnic groups. This study investigates how immigration-related factors shape the depression help-seeking behaviors of older Chinese Americans. METHODS: Data were collected from participants who reported experiencing any depressive symptoms in the Population-based Study of Chinese Elderly in Chicago (n = 907). Multinomial logistic regressions were conducted to examine the associations between immigration-related factors and help-seeking behaviors, including not seeking help (23.5%), seeking help from informal source(s) only (40%), seeking help from both informal and formal sources (28.7%), and seeking help from formal source(s) only (8.8%). RESULTS: Older Chinese Americans with lower levels of acculturation (OR = 0.88, 95% CI = 0.79-0.97) and those who lived in Chinatown (OR = 2.34, 95% CI = 1.21-4.52) were more likely to seek help from formal sources only (relative to not seeking any help). CONCLUSIONS: Older Chinese Americans with depressive symptoms predominately relied on informal sources of help, either solely or in combination with formal sources, to address their depressive symptoms. CLINICAL IMPLICATIONS: Leveraging informal support networks and ethnicity-specific resources represents a promising approach for this population.

[Methods for traditional Chinese medicine syndrome-based efficacy evaluation: a review].

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

Bifunctional Ru-Cluster-Decorated Co3 B-Co(OH)2 Hybrid Catalyst Synergistically Promotes NaBH4 Hydrolysis and Water Splitting.

Developing a highly efficient bifunctional catalyst for hydrolysis of metal hydrides and spontaneous hydrogen evolution reaction (HER) is essential for substituting conventional fuels for H2 production. Herein, Ru-cluster-modified Co3 B-Co(OH)2 supported on nickel foam (Ru/Co3 B-Co(OH)2 @NF) is constructed by electroless deposition, calcination and chemical reduction. The catalyst exhibits an excellent hydrogen generation rate (HGR) of 4989 mL min-1 g c a t a l y s t - 1 ${{{\rm g}}_{catalyst}^{-1}}$ and good reusability, superior to most previously reported catalysts. Besides, Ru/Co3 B-Co(OH)2 @NF displays a prominent hydrogen evolution reaction catalytic capability with a low overpotential of 153.0 mV at 100 mA cm-2 (50.5 mV at 10 mA cm-2 ), a small Tafel slope of 40.0 mV dec-1 and long-term stability (100 h@10 mA cm-2 ) in 1.0 M KOH. The excellent catalytic H2 generation capacity benefits from the rapid charge transfer promoted by metallic Co3 B, the synergistic catalytic effect of Co3 B-Co(OH)2 and Ru clusters, and the unique composite structure favorable for solute transport and gas emission.

Highly efficient bioconversion of icariin to icaritin by whole-cell catalysis.

BACKGROUND: Icaritin is an aglycone of flavonoid glycosides from Herba Epimedii. It has good performance in the treatment of hepatocellular carcinoma in clinical trials. However, the natural icaritin content of Herba Epimedii is very low. At present, the icaritin is mainly prepared from flavonoid glycosides by α-L-rhamnosidases and ß-glucosidases in two-step catalysis process. However, one-pot icaritin production required reported enzymes to be immobilized or bifunctional enzymes to hydrolyze substrate with long reaction time, which caused complicated operations and high costs. To improve the production efficiency and reduce costs, we explored α-L-rhamnosidase SPRHA2 and ß-glucosidase PBGL to directly hydrolyze icariin to icaritin in one-pot, and developed the whole-cell catalytic method for efficient icaritin production. RESULTS: The SPRHA2 and PBGL were expressed in Escherichia coli, respectively. One-pot production of icaritin was achieved by co-catalysis of SPRHA2 and PBGL. Moreover, whole-cell catalysis was developed for icariin hydrolysis. The mixture of SPRHA2 cells and PBGL cells transformed 200 g/L icariin into 103.69 g/L icaritin (yield 95.23%) in 4 h in whole-cell catalysis under the optimized reaction conditions. In order to further increase the production efficiency and simplify operations, we also constructed recombinant E. coli strains that co-expressed SPRHA2 and PBGL. Crude icariin extracts were also efficiently hydrolyzed by the whole-cell catalytic system. CONCLUSIONS: Compared to previous reports on icaritin production, in this study, whole-cell catalysis showed higher production efficiency of icaritin. This study provides promising approach for industrial production of icaritin in the future.

Bavachin protects against diet-induced hepatic steatosis and obesity in mice.

Non-alcoholic fatty liver disease (NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with NAFLD is rapidly increasing because of the obesity epidemic. There are currently no approved drugs that prevent or treat NAFLD. Recent evidence shows that bavachin, a flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and insulin sensitivity during preadipocyte differentiation, but the effect of bavachin on glucose and lipid metabolism remains unclear. In the current study we investigated the effects of bavachin on obesity-associated NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with bavachin (20 µM) significantly suppressed PA/OA or high glucose/high insulin-induced increases in the expression of fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore, bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3ß, improving the insulin signaling activity in the cells. In HFD-induced obese mice, administration of bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in body weight, liver weight, blood glucose, and liver and serum triglyceride contents. Moreover, bavachin administration significantly alleviated hepatic inflammation and ameliorated HFD-induced glucose intolerance and insulin resistance. We demonstrated that bavachin protected against HFD-induced obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that bavachin repressed the expression of lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion, bavachin attenuates hepatic steatosis and obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that bavachin is a potential drug for NAFLD therapy.

Isolated diffuse choroidal hemangioma without systemic symptoms: a case report.

BACKGROUND: Sturge-Weber syndrome is a nonhereditary congenital neurocutaneous syndrome characterized by a distinctive facial capillary malformation,neurological abnormalities, and ocular abnormalities such as glaucoma and choroidal hemangioma.It can be divided into different subtypes according to different clinical manifestations. It is rare for a patient to present with isolated difuse choroidal hemangioma and ipsilateral abnormal conjunctival and episcleral vessels without other systemic symptoms. CASE PRESENTATION: We report a 30-year-old man with isolated diffuse choroidal hemangioma in his right eye without systemic symptoms, such as vascular malformations in the skin or leptomeningeal angiomatosis. The only additional ophthalmic finding was ipsilateral abnormal conjunctival and episcleral vessels without glaucoma. However, there was no evidence of leptomeningeal angiomatosis or port-wine stain on the right side of the face, or glaucoma, which are common clinical manifestations of the Sturge-Weber syndrome (SWS).The absence of these characteristic symptoms did not preclude the diagnosis, and the patient could be diagnosed with a particular subtype of SWS. CONCLUSIONS: This is a rare case of documented isolated difuse choroidal hemangioma with ipsilateral abnormal conjunctival and episcleral vessels without glaucoma which we think it is belonging to a particular subtype of SWS.In addition to the traditional clinical manifestations, more and more atypical clinical manifestations are also accompanied by SWS, which requires our clinicians to continuously discover and report, so as to help more clinicians understand this disease.

Trust in physicians, health insurance, and health care utilization among Chinese older immigrants.

OBJECTIVE: Trust in physicians (TIP) plays a critical role in the health care utilization (HCU) of minority older adults and older immigrants. Although previous studies suggested that TIP was positively associated with primary care visits, negatively associated with Emergency Room (ER) visits and hospitalization among African Americans in the United States (U.S.), it is unclear whether and how TIP influences various types of HCU among Chinese older immigrants, a fast-growing group of minority older immigrants in the U.S. Furthermore, despite the important role insurance plays in HCU and health disparities, few studies have tested whether TIP influences the HCU of the insured and uninsured Chinese older immigrants differently. Therefore, this study aims to examine the role of TIP in three types of HCU (physician visits, ER visits, and hospitalization) among Chinese older immigrants and whether the associations differ by insurance status. DESIGN: The data were derived from the Population Study of ChINese Elderly in Chicago (PINE), N = 3,157. The sample is representative of Chinese older immigrants (60+ years) in Chicago. Guided by Andersen's behavioral model, hierarchical regression analyses examined the role of TIP in physician visits, ER visits, and hospitalization among Chinese older immigrants. An interaction term was added to examine whether the aforementioned associations differed by insurance status. RESULTS: TIP was positively associated with the likelihood of physician visits (Odds Ratio [OR] = 1.07, p < 0.001) but not with ER (OR = 1.02, p = 0.054) or hospitalization (OR = 1.01, p = 0.13). The results of the moderation analyses further showed that TIP was more positively associated with ER visits (OR=0.94, p=0.006) and hospitalization (OR = 0.93, p = 0.004) among the uninsured population, compared to those insured. CONCLUSIONS: TIP played an important role in facilitating primary care visits among Chinese older immigrants regardless of insurance status. Additionally, TIP facilitated the ER visit and hospitalization among uninsured Chinese older immigrants.

Ethnic enclaves, social capital, and psychological well-being of immigrants: the case of Chinese older immigrants in Chicago.

Objectives: Using a large sample of Chinese older immigrants in Chicago, this study asked two questions: (1) Is living in Chinatown associated with better psychological well-being? (2) What is the role of social capital in such an association?Methods: Data were derived from the Population Study of Chinese Elderly in Chicago (N = 3,105). Depression and quality of life (QoL) were compared between those who lived in Chinatown and those who didn't. Negative binomial regressions (for depression) and logistic regressions (for QoL) were performed to examine the associations between Chinatown residence, social capital, and the two outcomes.Results: Net of social capital and the control variables, living in Chinatown was marginally associated with fewer depressive symptoms (ß= -.137, p = .057), but a significantly lower likelihood of reporting good QoL (OR = .797, CI: .661-.962). Although various forms of social capital were projective of positive psychological well-being, given the overall low social capital of the Chinatown residents, they heightened the mental health risks of this population.Conclusion: The neighborhood context may function to reproduce social disadvantage among aging immigrant populations. The findings point to the importance of intervention at the mezzo level to improve the psychological wellbeing of this population.

Mapping the heterogeneity of global methane footprint in China at the subnational level.

Achieving the ambitious Global Methane Pledge announced in the Glasgow Climate Pact requires collaborative efforts from both the signatory countries and China which serves as the world's largest emitter. Considering the heterogeneity of economic structures within China and the relocation of emissions between regions via the global economic network, it is vital to investigate how China's methane emissions at the subnational level are linked to global final consumption. In this paper, we mapped global methane footprint in China from 2007 to2015 at the subnational level, by nesting China's interprovincial input-output tables into global multiregional input-output accounts and upscaling grid-level methane emission data of the Edgar database to the provincial level. Our results suggested that global methane footprint in China shifted westward, and the United States, European Union, Japan, and Hong Kong were the main drivers of China's local methane emissions. By illustrating the international and interprovincial trade flows of methane emissions, this study demonstrated that southeast coastal provinces were the hotspots for global methane footprint while middle inland provinces were the emission hotspots for China's domestic demands. We also showed how China's methane emissions were distributed through the nested global economic network to different economic agents. Moreover, emission trends of key exporting sectors for China's eight economic zones were detailed discussed. The outcome of this study may be fully supportive for identifying the heterogeneous effects of global methane footprint in China and implicative for interprovincial and international collaborations towards methane emission mitigation.

Aberrant dynamic structure-function relationship of rich-club organization in treatment-naïve newly diagnosed juvenile myoclonic epilepsy.

Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich-club organization-a core feature of the brain networks. Moreover, it is unclear how structure-function relationships dynamically change over time in JME. Here, we quantify the anatomical rich-club organization and dynamic structural and functional connectivity (SC-FC) coupling in 47 treatment-naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC-FC coupling were also calculated to examine the supporting of structure-function relationship to brain information transfer. The results showed that the anatomical rich-club organization was disrupted in the patient group, along with decreased connectivity strength among rich-club hub nodes. Furthermore, reduced SC-FC coupling in rich-club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor-cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC-FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The aberrant dynamic SC-FC coupling of rich-club organization suggests a selective influence of densely interconnected network core in patients with JME at the early phase of the disease, offering new insights and potential biomarkers into the underlying neurodevelopmental basis of behavioral and cognitive impairments observed in JME.

Radicals Scavenging MOFs Enabling Targeting Delivery of siRNA for Rheumatoid Arthritis Therapy.

Macrophages play essential roles in the progression of rheumatoid arthritis (RA), which are polarized into the pro-inflammatory M1 phenotype with significant oxidative stress and cytokines excretion. Herein, an active targeting nanomedicine based on metal-organic frameworks (MOFs) to re-educate the diseased macrophages for RA therapy is reported. The MOFs are prepared via coordination between tannic acid (TA) and Fe3+ , and anti-TNF-α siRNA is loaded via a simple sonication process, achieving high loading capacity comparable to cationic vectors. The MOFs show excellent biocompatibility, and enable rapid endo/lysosome escape of siRNA via the proton-sponge effect for effective cytokines down-regulation. Importantly, such nanomedicine displays intrinsic radicals scavenging capability to eliminate a broad spectrum of reactive oxygen and nitrogen species (RONS), which in turn repolarizes the M1 macrophages into anti-inflammatory M2 phenotypes for enhanced RA therapy in combination with siRNA. The MOFs are further modified with bovine serum albumin (BSA) to allow cascade RA joint and diseased macrophages targeted delivery. As a result, an excellent anti-RA efficacy is achieved in a collagen-induced arthritis mice model. This work provides a robust gene vector with great translational potential, and offers a vivid example of rationally designing MOF structure with multifunctionalities to synergize with its payload for enhanced disease treatment.

G-quadruplex DNA: a novel target for drug design.

G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design. In this review, we summarize the detection method and the structure of G4, highlighting some non-canonical G4 DNA structures, such as G4 with a bulge, a vacancy, or a hairpin. Subsequently, the functions of G4 DNA in physiological processes are discussed, especially their regulation of DNA replication, transcription of disease-related genes (c-MYC, BCL-2, KRAS, c-KIT et al.), telomere maintenance, and epigenetic regulation. Typical G4 ligands that target promoters and telomeres for drug design are also reviewed, including ellipticine derivatives, quinoxaline analogs, telomestatin analogs, berberine derivatives, and CX-5461, which is currently in advanced phase I/II clinical trials for patients with hematologic cancer and BRCA1/2-deficient tumors. Furthermore, since the long-term stable existence of G4 DNA structures could result in genomic instability, we summarized the G4 unfolding mechanisms emerged recently by multiple G4-specific DNA helicases, such as Pif1, RecQ family helicases, FANCJ, and DHX36. This review aims to present a general overview of the field of G-quadruplex DNA that has progressed in recent years and provides potential strategies for drug design and disease treatment.

Angiotensin Receptor Blocker is Associated with a Lower Fracture Risk: An Updated Systematic Review and Meta-Analysis.

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in the treatment of hypertension. Hypertension is often accompanied by osteoporosis. However, the relationship between ACEI/ARB and fractures remains controversial. The purpose of this meta-analysis was to update the potential relationship between ACEI/ARB and fractures. Methods: This meta-analysis was identified through PubMed, EMBASE, Cochrane Library, and Web of Science. Related studies about ACEI/ARB with the risk of fracture were published from inception to June 2022. Results: Nine qualified prospective designed studies, involving 3,649,785 subjects, were included in this analysis. Overall, the RRs of ACEI compared with the nonusers were 0.98 (95% CI: 0.88, 1.10; P < 0.001) for composite fractures and 0.96 (95% CI: 0.87, 1.05; P=0.048) for hip fractures; the RRs of ARB compared to the nonusers were 0.82 (95% CI: 0.73, 0.91; P < 0.001) for composite fractures and 0.85 (95% CI: 0.74, 0.97; P=0.028) for hip fractures. Furthermore, in the subgroup analysis, male may benefit from ARB (RR = 0.65, 95% CI: 0.49, 0.89, P=0.028), and the European may also benefit from ARB (RR = 0.86, 95% CI: 0.80, 0.93, P=0.015). Conclusions: ACEI usage will not decrease the risk of osteoporosis fracture. On the contrary, ARB usage can decrease the risk of total fracture and hip fracture, especially for males and Europeans. Compared with ACEI, for patients at higher risk of fracture in cardiovascular diseases such as hypertension, the protective effect of ARB should be considered.

Clinicopathological and prognostic values of PD-L1 expression in oesophageal squamous cell carcinoma: a meta-analysis of 31 studies with 5368 patients.

Several immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1)/programmed death 1 have successfully improved the prognosis of oesophageal squamous cell carcinoma (ESCC) with approval in certain countries. However, whether the expression of PD-L1 is associated with the degree of benefit is unclear yet and a unified standard of antibody and cut-off value of PD-L1 detection is also lacking. The current meta-analysis then aimed to explore the association between PD-L1 expression and clinicopathological features as well as prognosis in ESCC.A systematic search on PubMed, Embase, Cochrane Library and Web of Science databases was performed up to 30 March 2021. The correlation between PD-L1 expression and clinicopathological features, as well as prognosis in ESCC, was estimated with the random-effects model.A total of 5368 patients from 31 retrospective studies were enrolled. The overexpression of PD-L1 was significantly associated with lymph node metastasis (OR 1.342, 95% CI 0.995 to 1.809, p=0.050) and distant metastasis (OR 1.516, 95% CI 1.001 to 2.294, p=0.050). The pooled HR showed that PD-L1 overexpression was significantly correlated with poor overall survival (OS) of patients with ESCC (HR 1.306, 95% CI 1.108 to 1.539, p<0.010) but not disease-free survival (DFS) (HR 1.180, 95% CI 0.937 to 1.487, p=0.160). Heterogeneity decreased significantly in subgroup analyses. The overexpression of PD-L1 was associated with poor DFS at the cut-off point of ≥1% (HR 1.642, 95% CI 1.367 to 1.973, p<0.010; I2=0%) and worse OS at the cut-off point of ≥10% (HR 1.575, 95% CI 1.175 to 2.111, p<0.010; I2=0%).The overexpression of PD-L1 was correlated with lymph node and distant metastasis as well as poor survival of ESCC.

Advantages of McKeown minimally invasive oesophagectomy for the treatment of oesophageal cancer: propensity score matching analysis of 169 cases.

BACKGROUND: Oesophagectomy, the gold standard for oesophageal cancer treatment, causes significantly high morbidity and mortality. McKeown minimally invasive oesophagectomy (MIE) is preferred for treating oesophageal malignancies; however, limited studies with large sample sizes focusing on the surgical and oncological outcomes of this procedure have been reported. We aimed to compare the clinical safety and efficacy of McKeown MIE with those of open oesophagectomy (OE). PATIENTS AND METHODS: Overall, 338 oesophageal cancer patients matched by gender, age, location, size, and T and N stages (McKeown MIE: 169 vs OE: 169) were analysed. The clinicopathologic features, operational factors, postoperative complications, and prognoses were compared between the groups. RESULTS: McKeown MIE resulted in less bleeding (200 mL vs 300 mL, p<0.01), longer operation time (335.0 h vs 240.0 h, p<0.01), and higher number of harvested lymph nodes (22 vs 9, p<0.01) than OE did. Although the rate of recurrent laryngeal nerve injury in the two groups was not significantly different, incidence of anastomotic leakage (8 vs 24, p=0.003) was significantly lower in the McKeown MIE group. In addition, patients who underwent McKeown MIE had higher 5-year overall survival than those who underwent OE (69.9% vs 40.4%, p<0.001). CONCLUSION: McKeown MIE is proved to be feasible and safe to achieve better surgical and oncological outcomes for oesophageal cancer compared with OE.

Coping repertoires and psychological well-being of Chinese older immigrants in the United States.

OBJECTIVES: This study examines (1) the overall structures of multifaceted coping resources, that is, coping repertoires, among Chinese older immigrants in the United States, (2) the optimal coping repertoire that is associated with best psychological outcomes of these older immigrants, and (3) the most effective coping repertoire in different adversities. METHOD: Using data from 2,923 Chinese older immigrants in Chicago, Latent Class Analysis (LCA) was performed to identify the overall coping repertoires of U.S. Chinese older adults. Negative binomial and logistic regressions were used to examine associations between coping repertoires and depression and Quality of Life (QoL), respectively. We further tested whether coping repertories moderate the relationships between adversities in health, economic, and social domains, and the two psychological outcomes. RESULTS: LCA revealed four types of coping repertories: low-resource (43%), spouse-oriented (32%), community-oriented (15%), and multi-source coping (10%). Overall, Chinese older immigrants who had the multi-source coping repertoire reported the best psychological outcomes. The community-oriented and multi-source coping repertories had significantly stronger buffering effects on psychological well-being among individuals with IADL difficulties or low acculturation. However, spouse-oriented coping intensified the association between ADL difficulties and depression, and community-oriented coping intensified the association between poorer subjective health and lower quality of life. CONCLUSION: This study revealed overall low coping repertories of Chinese older immigrants, suggesting the most optimal coping repertories should consist of both intrinsic and extrinsic coping sources. The findings further show that relying on limited sources might be harmful to older immigrants' mental health.

Sources of Intergenerational Conflict in Chinese Immigrant Families in the United States.

Studies of family relations have not kept pace with the acceleration of international migration. To address this gap, this study relied on a survey of 545 Chinese immigrants in Chicago who reported information of 869 older parents to examine the sources of intergenerational conflict in five domains: norms/values, relationship itself, money, health, and parenting. The results of logistic regression showed that maintaining one's traditional culture, in the form of endorsing a sense of filial obligation, was a significant protective factor against all types of conflict. Immigrants with a higher level of acculturation were more likely to report conflict regarding norms/values and relationship itself, but not more so regarding practical issues such as health, money, and parenting. Helping parents with ADLs, not IADLs, was associated with more conflict regarding monetary and health issues. Immigrants' greater sense of mastery was associated with a lower chance of reporting norm/value-related intergenerational conflict.

Depletion of miR-21 in dendritic cells aggravates renal ischemia-reperfusion injury.

Dendritic cells (DCs) play an important role in the pathophysiology of renal ischemia-reperfusion injury (IRI). The mechanisms underlying DCs phenotypic modulation and their function are not fully understood. In this study, we examined the effect of miR-21 on the phenotypic modulation of DCs in vitro and in vivo, and further investigated the impact of miR-21-overexpression DC or miR-21-deficient DC on renal IRI. We found that treatment with hypoxia/reoxygenation (H/R) suppressed miR-21 expression in bone marrow-derived dendritic cells (BMDCs), and significantly increased the percentage of mature DCs (CD11c+ /MHC-II+ /CD80+ ). Using a selection of microRNA mimics, we successfully induced the upregulation of miR-21 in BMDCs, which induced immature DC phenotype and an anti-inflammatory DC response. However, deletion of miR-21 in BMDCs promoted maturation of DCs under H/R. Adoptive transfer of miR-21-overexpression BMDCs could alleviate renal IR-induced pro-inflammatory cytokines production and acute kidney injury (AKI). Mice with miR-21 deficiency in DCs subjected to renal IR showed more severe renal dysfunction and inflammatory response compared with wild-type mice. In addition, chemokine C receptor 7 (CCR7), a surface marker of mature DC, was a target gene of miR-21, and silencing of CCR7 in BMDCs led to reduced mature DCs under H/R. In conclusion, our findings highlight miR-21 as a key regulator of DCs subset phenotype and a potential therapeutic target in renal IRI.