Body weight, weight change and the risk of cardiovascular disease in patients with hypertension: a primary-care cohort study.

BACKGROUND/OBJECTIVES: Obesity and cardiovascular disease (CVD) often co-occur. However, the effects of excessive body weight and weight change on CVD in patients with hypertension are not clearly established. We examined the associations of BMI, weight change and the risk of CVD in patients with hypertension. SUBJECTS/METHODS: Our Data were drawn from the medical records of primary-care institutions in China. A total of 24,750 patients with valid weight measurements attending primary healthcare centers were included. Body weight were grouped in BMI categories of underweight ( < 18.5 kg/m2), healthy weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2) and obesity ( ≥ 25.0 kg/m2). Weight change over 12 months was divided into: gain >4%, gain 1-4%, stable (-1 to 1%), loss 1-4%, and loss ≥4%. Cox regression analyses were used to estimate hazard ratio (HR) and 95% confidence interval (95% CI) between BMI, weight change and the risk of CVD. RESULTS: After multivariable adjustment, patients with obesity were related to higher risks of CVD (HR = 1.48, 95% CI: 1.19-1.85). Higher risks were seen in participants with loss ≥4% and gain >4% of body weight compared to stable weight (loss ≥4%: HR = 1.33, 95% CI: 1.04-1.70; gain >4%: HR = 1.36, 95% CI: 1.04-1.77). CONCLUSION: Obesity and weight change of loss ≥4% and gain >4% were related to higher risks of CVD. Close monitoring and appropriate interventions aimed at achieving an optimal weight are needed to prevent adverse cardiovascular outcomes for patients with hypertension.

Association between obesity indicators and cardiometabolic disease in Chinese adults.

BACKGROUND: Obesity is an established risk factor for cardiometabolic disease. Different measurements of obesity with cardiometabolic disease have been compared in recent studies in Western countries. However, obesity-related criteria for the Chinese population differ from the standard World Health Organization guidelines, and similar research in Chinese adults is limited. MEASURES: Data were obtained from a comprehensive intervention project involving a community population with cardiovascular and cerebrovascular risk factors in Shenzhen in 2015. A total of 4,000 participants (1,605 men and 2,395 women) with a mean age of 56.01±9.78 years were included in this study. Categorical data are reported as percentages, and continuous data are reported as mean ± standard deviation. Logistic regression analyses were conducted to examine the associations of body mass index (BMI), waist circumference (WC), and neck circumference (NC) with hypertension, diabetes, and dyslipidemia among Chinese adults. RESULTS: The participants had a mean BMI of 24.25±3.33 kg/m2, mean NC of 33.59±4.16 cm, and mean WC of 82.44±9.84 cm (men: 85.46±9.10 cm, women: 80.40±9.81 cm). Blood pressure, plasma glucose, and lipid levels in the BMI, WC, and NC groups were statistically significant (p < 0.05). BMI, WC, and NC were positively correlated with systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglyceride and negatively correlated with low-density lipoprotein cholesterol (p < 0.05), while the risk of hypertension, diabetes, and dyslipidemia increased with an increase in BMI, WC, and NC (p < 0.05). One SD of BMI, WC, and NC resulted in an increase of 41%, 22%, and 31% risk of hypertension; 45%, 34%, and 47% risk of diabetes; and 37%, 32%, and 23% risk of dyslipidemia, respectively. CONCLUSIONS: Compared to BMI and NC, WC was more strongly associated with cardiometabolic diseases in Chinese adults.

Visit-to-visit variability of blood pressure and risk of macrovascular and microvascular complications in patients with type 2 diabetes: A Chinese primary-care cohort study.

BACKGROUND: We evaluated the effects of visit-to-visit variability of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on macrovascular and microvascular complications among patients with type 2 diabetes. METHODS: A total of 11 043 patients with type 2 diabetes from primary healthcare institutions between January 2010 and June 2020 were included. The visit-to-visit blood pressure variability was calculated using three metrics: SD, coefficient of variation (CV), and average real variability (ARV), obtained over a 12-month measurement period. The associations of visit-to-visit blood pressure variability with macrovascular and microvascular complications were evaluated using multivariate-adjusted Cox proportional hazards models, and hazard ratio (HR) with 95% confidence interval (CI) were reported. RESULTS: There were 330 macrovascular events and 542 microvascular events. Compared to those for participants with the lowest quartile of SD of SBP and DBP, increased risks were observed in patients with the highest quartile of SD of SBP and DBP for macrovascular complications (SD-SBP: HR = 1.78, 95% CI: 1.24-2.57; SD-DBP: HR = 2.20, 95% CI: 1.50-3.25) and microvascular complications (SD-SBP: HR = 1.85, 95% CI: 1.39-2.46; SD-DBP: HR = 1.82, 95% CI: 1.36-2.44). CV and ARV of SBP and DBP also had statistically significant associations with macrovascular and microvascular complications. The optimal variability of blood pressure target was SD of SBP <6.45 mm Hg and SD of DBP <4.81 mm Hg. CONCLUSIONS: Visit-to-visit blood pressure variability may be a potential predictor for macrovascular and microvascular complications in patients with type 2 diabetes.

The Risks of Cardiovascular Disease Following Weight Change in Adults with Diabetes: A Cohort Study and Meta-analysis.

CONTEXT: Weight management is recognized as critical in reducing cardio-metabolic risk factors for adults with diabetes, but the effects of weight change on cardiovascular disease in patients with diabetes are unknown. OBJECTIVE: To evaluate 18-month weight change and subsequent risk of macrovascular and microvascular complications in established individuals with type 2 diabetes. DESIGN AND SETTING: This study consisted of a cohort study and a meta-analysis. In the cohort study, weight change over 18 months was divided into: gain ≥5%, gain 1%-5%, stable (-1%-1%), loss 1%-5%, and loss ≥5%. Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). We then used random-effect models to pool the results combing our study with other relevant studies. RESULTS: In the cohort study, 8920 participants with valid weight measurements were included. Compared with patients with stable weight, higher risks were seen in those with weight change for total vascular complications (gain ≥5%: HR=1.43, 95% CI: 1.10-1.85; gain 1-5%: HR=1.44, 95% CI: 1.02-2.03; loss ≥5%: HR=1.58, 95% CI: 1.20-2.08), macrovascular complications (gain ≥5%: HR=1.84, 95% CI: 1.16-2.91; loss 1-5%: HR=1.91, 95% CI: 1.06-3.43; loss ≥5%: HR=2.18, 95% CI: 1.36-3.49) and microvascular complications (loss ≥5%: HR=1.48, 95% CI: 1.06-2.06). Meta-analysis also showed similar results. CONCLUSIONS: Weight gain and loss over 18 months among patients with type 2 diabetes, especially weight change ≥5%, may be a warning sign of adverse cardiovascular outcomes.

The Risks of Cardiovascular Disease Following Weight Change in Adults with Diabetes: A Cohort Study and Meta-analysis (jc.2022-01089).

CONTEXT: Weight management is recognized as critical in reducing cardio-metabolic risk factors for adults with diabetes, but the effects of weight change on cardiovascular disease in patients with diabetes are unknown. OBJECTIVE: To evaluate 18-month weight change and subsequent risk of macrovascular and microvascular complications in established individuals with type 2 diabetes. DESIGN AND SETTING: This study consisted of a cohort study and a meta-analysis. In the cohort study, weight change over 18 months was divided into: gain ≥5%, gain 1%-5%, stable (-1%-1%), loss 1%-5%, and loss ≥5%. Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). We then used random-effect models to pool the results combing our study with other relevant studies. RESULTS: In the cohort study, 8920 participants with valid weight measurements were included. Compared with patients with stable weight, higher risks were seen in those with weight change for total vascular complications (gain ≥5%: HR=1.43, 95% CI: 1.10-1.85; gain 1-5%: HR=1.44, 95% CI: 1.02-2.03; loss ≥5%: HR=1.58, 95% CI: 1.20-2.08), macrovascular complications (gain ≥5%: HR=1.84, 95% CI: 1.16-2.91; loss 1-5%: HR=1.91, 95% CI: 1.06-3.43; loss ≥5%: HR=2.18, 95% CI: 1.36-3.49) and microvascular complications (loss ≥5%: HR=1.48, 95% CI: 1.06-2.06). Meta-analysis also showed similar results. CONCLUSIONS: Weight gain and loss over 18 months among patients with type 2 diabetes, especially weight change ≥5%, may be a warning sign of adverse cardiovascular outcomes.

Differences in the Distribution of Species, Carbapenemases, Sequence Types, Antimicrobial Heteroresistance and Mortality Rates Between Pediatric and Adult Carbapenemase-Producing Enterobacterales in Bloodstream Infections.

The dissemination of carbapenemase-producing Enterobacterales (CPE) is worrisome given their scarce treatment options. CPE bloodstream infections (BSIs) had a high mortality rate in adults, and there was little data on pediatric CPE-BSIs around the world. We comprehensively explored the differences in the clinical and microbiological characteristics between pediatric and adult CPE-BSIs. Forty-eight pediatric and 78 adult CPE-BSIs cases were collected. All-cause 30 day-mortality in children with CPE-BSIs (14.6%, 7/48) was significantly lower than that in adult patients (42.3%, 33/78, p = 0.001). The subgroup in adults empirically treated with tigecycline as an active drug displayed a significantly higher 30-days crude mortality (63.3%, 19/30) than the subgroup treated without tigecycline (29.2%, 14/48, p = 0.003). K. pneumoniae was the most prevalent species in both the pediatric (45.8%, 22/48) and adult populations (64.1%, 50/78), with discrepant carbapenemase genes in each population: 95.4% (21/22) of the pediatric K. pneumoniae isolates carried bla NDM, while 82.0% (41/50) of the adult strains harbored bla KPC. The ratio of E. coli in children (37.5%) was significantly higher than that in adults (12.8%, p = 0.002). In both populations, the majority of E. coli expressed bla NDM, particularly bla NDM-5. With statistical significance, bla NDM was much more common in children (95.8%, 46/48) than in adults (34.6%, 27/78). The rate of multiple-heteroresistance phenotypes in children was as high as 87.5%, which was much lower in adults (57.1%). Agar dilution checkboard experiment against one pediatric carbapenemase-producing E. coli isolates showed that the combination of amikacin and fosfomycin yielded an additive effect. Overall, K. pneumoniae was the most common CPE-BSIs pathogen in both populations, with NDM-producing K. pneumoniae and KPC-producing ST11 K. pneumoniae being the most prevalent species in children and adults, respectively. E. coli was more prevalent in children than in adults, yet bla NDM-5 was the most common carbapenem-resistant mechanism in E. coli in both populations. The wide range of multiple-heteroresistance combination traits found in different pathogen species from different host populations should provide a good foundation for future combination therapy design. Further investigations from more CPE isolates of various species are needed to evaluate the possible in vitro partial synergy of the amikacin and fosfomycin combination.

HHLA2 Activates the JAK/STAT Signaling Pathway by Binding to TMIGD2 in Hepatocellular Carcinoma Cells.

HHLA2, a member of the B7 family of immune checkpoint players, has been implicated in various cancers. The study set to determine the expression and biological function of HHLA2 in hepatocellular carcinoma (HCC), and its connection to TMIGD2. First, after HHLA2 knockdown or overexpression in Huh-7 or HepG2 cells, we co-cultured T cells with HCC cells after transfection for 48 h. T cell proliferation and cytokine release were detected using flow cytometry and the FlowCytomix assay kit. Subsequently, we screened differentially expressed genes in cells overexpressing or under-expressing HHLA2 using GSEA database and analyzed the pathways enriched by them. We further detected the nuclear translocation of STAT3 and STAT2 using immunofluorescence. After that, we observed the subcellular localization of HHLA2 and TMIGD2 in HCC cells by laser confocal microscopy, followed by RIP and rescue experiments. We found that the proliferation of T cells and the release of cytokines were significantly reduced after co-culture with HCC cells overexpressing HHLA2, while co-culture with cells low in HHLA2 expression had the opposite results. HHLA2 bound to TMIGD2, thus inhibiting T cell proliferation and activation. Overexpression of HHLA2 significantly promoted the nuclear translocation of STAT2 and STAT3, thereby activating the JAK/STAT pathway. Subsequently, we showed that the immune tolerance of HCC cells was significantly attenuated after using a JAK/STAT signaling pathway antagonist. Aberrant overexpression of HHLA2 activates the JAK/STAT signaling pathway by binding to TMIGD2, thereby promoting immune tolerance in HCC cells.

Interferon Gamma-Induced Interferon Regulatory Factor 1 Activates Transcription of HHLA2 and Induces Immune Escape of Hepatocellular Carcinoma Cells.

Immunosuppression developed by cancer cells remains a leading cause of treating failure of immunotherapies. This study aimed to explore the function of human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), an immune checkpoint molecule from the B7 family, in the immune escape in hepatocellular carcinoma (HCC). Mouse models with primary HCC or with xenograft tumors were established. The portion of tumor-associated macrophages (TAMs) and the level of PD-L1 in the tumor tissues were examined. THP-1 cells were treated with PMA to obtain a macrophage-like phenotype. The PMA-treated THP-1 cells were co-cultured with the HCC cells in Transwell chambers to examine the function of HHLA2 in chemotactic migration and polarization of macrophages. HHLA2 expression was correlated with infiltration of immune cells, especially macrophages, and was linked to poor prognosis of patients with HCC. HHLA2 knockdown reduced incidence rate of primary HCC in mice. It also reduced tumor metastasis, the portion of M2 macrophages, and the expression of PD-L1 in primary and xenograft tumors. In vitro, HHLA2 upregulation increased expression of PD-L1 in HCC cells indirectly by inducing M2 polarization and chemotactic migration of macrophages. Interferon gamma (IFNG) enhanced expression of interferon regulatory factor 1 (IFR1) in HCC cells, and IFR1 bound to the promoter region of HHLA2 to activate HHLA2 expression. This study suggested that the IFNG/IFR1/HHLA2 axis in HCC induces M2 polarization and chemotactic migration of macrophages, which leads to immune escape and development of HCC.

Prognosis Value of microRNA-3677-3p in Lung Adenocarcinoma and Its Regulatory Effect on Tumor Progression.

PURPOSE: Lung adenocarcinomas (LUAD) was the most common subtype of lung cancer, and may result in a poor prognosis. This study was designed to explore the role of miR-3677-3p in LUAD and discuss in what way it functions in LUAD. MATERIALS AND METHODS: We used RT-qPCR method to detect the expression levels of miR-3677-3p in 105 pairs of LUAD tissues and noncancerous tissues, as also as in LUAD cells. We used χ 2 test to analyze the correlation between miR-3677-3p level and the clinical data. The prognosis significance of miR-3677-3p was inferred with Kaplan-Meier and multivariate Cox regression assays. Biological functions of LUAD cells were accessed by cell counting kit-8, transwell migration and invasion assay. The target gene of miR-3677-3p was investigated by luciferase activity assay. RESULTS: miR-3677-3p represented an ascendant expression in LUAD tissue specimens and cells. miR-3677-3p expression was associated with the TNM stage and with solitary metastasis. Over-expression of miR-3677-3p can shorten the overall survival period of LUAD patients when compared with low expression. Knockdown of miR-3677-3p suppressed the biology function of NSCLC cells including proliferation, migration, and invasion. KLF12 was a target gene of miR-3677-3p. CONCLUSION: miR-3677-3p represents as a potential prognostic biomarker for LUAD. miR-3677-3p can promote LUAD progression by targeting KLF12.

Clinical and Microbiological Characterization of Carbapenem-Resistant Enterobacteriales: A Prospective Cohort Study.

Aim: We aim to depict the clinicoepidemiological and molecular information of carbapenem-resistant Enterobacteriales (CRE) in Chongqing, China. Methods: We performed a prospective, observational cohort study, recruiting inpatients diagnosed with CRE infections from June 1, 2018, to December 31, 2019. We carried out strain identification and molecular characterization of CRE. eBURST analysis was conducted to assess the relationships among the different isolates on the basis of their sequence types (STs) and associated epidemiological data using PHYLOViZ. Clinical parameters were compared between the carbapenemase-producing Enterobacteriales (CPE) and non-CPE group. Findings: 128 unique CRE isolates from 128 patients were collected during the study period: 69 (53.9%) CPE and 59 (46.1%) non-CPE. The majority of CPE isolates were bla KPC-2 (56.5%), followed by bla NDM (39.1%) and bla IMP (5.8%). Klebsiella pneumoniae carbapenemase (KPC)-producing clonal group 11 Klebsiella pneumoniae (K. pneumoniae) was the most common CPE. Antibiotic resistance was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE infection were ICU admission and hepatobiliary system diseases. Although, there was no significant difference in desirability of outcome ranking (DOOR) outcomes between the two groups. At 30 days after index culture, 35 (27.3% ) of these patients had died. Conclusion: CRE infections were related to high mortality and poor outcomes, regardless of CRE subgroups. CPE were associated with prolonged ICU stays and had different clinical and microbiological characteristics than non-CPE. The identification of CPE/non-CPE and CRE resistance mechanisms is essential for better guidance of the clinical administration of patients with CRE infections.

Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro.

BACKGROUND: Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011-2018. METHODS: We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011-2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from "Resistant" or "Intermediate" with CAZ or ATM alone to "Susceptible" with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone. RESULTS: For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03-64, 1-1024, 0.016-64, and 0.06-64 µg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P < 0.001), and MIC50 (2 µg/mL vs. 8 µg/mL, P < 0.05) when compared to CAZ. According to our definition, CAZ-AVI was more active in vitro than CAZ alone for 81.58% (62/76) of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79% vs.10.53%, P < 0.001) and MIC50 (2 µg/mL vs. 64 µg/mL, P < 0.001) when compared to ATM. According to our definition, ATM-AVI was also more active in vitro than ATM alone for 94.74% (72/76) of the isolates. CONCLUSIONS: AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

Treatment of Bronchopleural Fistula with Carbolic Acid instilled through Bronchofiberscope in post-pulmonectomy patients.

OBJECTIVE: To investigate the efficacy of carbolic acid treatment of bronchopleural fistula (BPF) using bronchofiberscope (BFS) in post-pulmonectomy patients. METHOD: Twelve patients with post-pulmonectomy BPF were enrolled in this study at the Liaoning Tumor Hospital between February 2009 and March 2012. Three patients had BPF after the right pneumonectomy, six patients after left pneumonectomy, one patient after the right middle and low lobectomy and two patients after left upper lobectomy. BPF patients were instilled with 100 % carbolic acid (0.5-1 ml one time every week) through BFS on the mucosal surface around the fistula, and the bubble disappearance was monitored. Treatment was repeated if the bubble remained. RESULTS: No haemorrhage, severe dyspnea or SpO2 declines occurred in all the 12 patients during the bronchoscopic therapy. BPF orifices were closed in five patients after receiving 5 treatments with carbolic acid, 1 patient received 2 treatments, 1 patient was given 3 treatments, 2 patients received 4 treatments and 3 patients were given 7 treatments. Follow-up was conducted for six months following bronchoscopy. The average treatment and fistula closure time were calculated from the data collected as 20 min and 30 days, respectively, and the cure rate was 100 %. Hematoxylin-eosin (HE) staining results revealed that the white flat hyperplasia tissue after carbolic acid treatment was inflammatory granulation tissue. CONCLUSION: Our results revealed that instillation of 100 % carbolic acid with BFS to treat BPF was 100 % effective, which can be a support for post-pulmonectomy BPF.

Antitumor effect of recombinant human endostatin combined with cisplatin on rats with transplanted Lewis lung cancer.

OBJECTIVE: To observe the antitumor effect and mechanism of recombinant human endostatin (Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. METHODS: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm(3). Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg kg(-1) d(-1) for 10 d. Group C was given the injection of Endostar 5 mg kg(-1) d(-1) combined with intraperitoneal injection of cisplatin 5 mg kg(-1) d(-1) for 10 d. All the rats in three groups were executed the day after the 10 d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor (VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density (MVD) in each group. RESULTS: The volume and mass of tumor in Groups B and C were significantly lower than Group A (P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B (P < 0.05). The antitumor rate in Group C was significantly higher than Group B (P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B (P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A (P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. CONCLUSIONS: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.