The circRNA_102911/miR-129-5p/SOX6 axis is involved with T lymphocyte immune function in elderly patients with laparoscopic left hepatectomy for hepatolithiasis.

The aim of the present study was to investigate the impact of laparoscopic left hepatectomy (LLH) for hepatolithiasis on the T lymphocyte immune changes of elderly patients and to analyze underlying mechanisms of action behind these changes. A total of 164 patients who underwent LLH due to left-sided hepatolithiasis were recruited. In terms of T lymphocyte immune changes, it was found that firstly, the basic quantity of peripheral lymphocytes in the elderly group was significantly lower than that in a younger preoperative group. Secondly, after surgical trauma, the immune function of T lymphocytes had a significant decline and lasted longer when compared with younger patients, which was reflected by the perioperative changes in the T lymphocyte proliferative ability, levels of IL-2 secreted by T lymphocytes and the percentage of CD3+/CD4+ T lymphocytes in the peripheral blood. Circular RNA (circRNA) 102911 (102911) was upregulated and microRNA (miR)-129-5p was downregulated in CD3+/CD4+ T lymphocytes from elderly patients with LLH for hepatolithiasis. Furthermore, the overexpression of 102911 inhibited the proliferation of CD3+/CD4+ T lymphocytes as well as promoting cell apoptosis, with the opposite effects being observed on knockdown of 102911. miR-129-5p is involved in the proliferation and apoptosis of CD3+/CD4+ T lymphocytes and may be a promising target of 102911. Moreover, SOX6 is a downstream molecule of miR-129-5p. Immune function and number of T lymphocytes decreased significantly after surgical trauma compared to younger patients, and this decline lasted longer in older patients treated with LLH for hepatolithiasis. The 102911/miR-129-5p/SOX6 axis was found to be involved in T lymphocytes immune function, which provided a novel insight for the treatment of elderly patients with hepatolithiasis.

Clinical Efficiency of Vasopressin or Its Analogs in Comparison With Catecholamines Alone on Patients With Septic Shock: A Systematic Review and Meta-Analysis.

BACKGROUND: Vasopressin is an efficient remedy for septic shock patients as its great capacity in promoting hemodynamic stabilization. The aim of current systematic review and meta-analysis is to compare the clinical efficiency of vasopressin or its analogs with sole catecholamines on patients with septic shock. METHODS: A systematic search of Cochrane Library, EMBASE, and PubMed online databases was performed up to 30 Oct 2019 to identify randomized controlled trials comparing use of vasopressin or its analogs (e.g., terlipressin, selepressin) with administration of catecholamines alone. RESULTS: We included 23 RCTs with 4,225 patients in the current study. Compared with solely use of catecholamines, administration of vasopressin or its analogs was not associated with reduced 28-day or 30-day mortality among patients with septic shock [RR=0.94 (95% CI, 0.87-1.01), P=0.08, I2 = 0%]. The result of primary endpoint remained unchanged after conducting sensitivity analysis. Despite a significantly higher risk of digital ischemia in patients receiving vasopressin or its analogs [RR=2.65 (95% CI, 1.26-5.56), P < 0.01, I2 = 48%], there was no statistical significance in the pooled estimate for other secondary outcomes, including total adverse events, arrhythmia, acute myocardial infarction (AMI) and cardiac arrest, acute mesenteric ischemia, ICU/hospital length of stay, and mechanical ventilation (MV) duration. CONCLUSIONS: The administration of vasopressin or its analogs was not associated with reduced 28-day or 30-day mortality among patients with septic shock, while an increased incidence of digital ischemia should be noted in patients receiving agonists for vasopressin receptors.

MiRNA-221 protects islet ß cell function in gestational diabetes mellitus by targeting PAK1.

To elucidate the potential function of miRNA-221 in gestational diabetes mellitus (GDM) and the underlying mechanism. MiRNA-221 level was analyzed in the microarray containing placental tissues of GDM rats. After constructing GDM model in rats, miRNA-221 level in placental tissues of GDM rats or controls was determined as well. The relationship between miRNA-221 level and blood glucose in GDM rats was analyzed by Spearman correlation test. Regulatory effects of miRNA-221 on proliferation, apoptosis and insulin secretion in INS-1 cells were assessed. Through dual-luciferase reporter gene assay, the direct target of miRNA-221, PAK1 was identified. At last, potential influences of miRNA-221/PAK1 axis on INS-1 cell phenotypes were determined. MiRNA-221 was downregulated in placental tissues of GDM rats, and its level was negatively correlated to that of blood glucose level in GDM rats. Overexpression of miRNA-221 stimulated insulin secretion, cell proliferation and suppressed apoptosis in INS-1 cells. Knockdown of miRNA-221 achieved the opposite results. PAK1 was proved as the direct target of miRNA-221. Notably, PAK1 was able to reverse regulatory effects of miRNA-221 on INS-1 cell phenotypes. MiRNA-221 regulates proliferation, apoptosis and insulin secretion in islet ß cells through targeting PAK1, thus protecting GDM-induced islet dysfunction.

Hypercholesterolaemia increases the risk of high­turnover osteoporosis in men.

As the incidence of osteoporosis (OP) and hypercholesterolaemia in men has increased, male OP has drawn more attention from clinicians worldwide. The present study sought to investigate the effects of cholesterol on male bone. Between July 2015 and October 2015, 216 men (aged ≥18 years) were recruited for this cross­sectional study. To test our clinical hypothesis, we designed two male animal models: Exogenous hypercholesterolaemia induced by a high­cholesterol diet (HCD) and endogenous hypercholesterolaemia induced by apolipoprotein E (ApoE) knockout. Finally, the direct effects of cholesterol on osteoblasts were observed in cell experiments. In our clinical studies, men with hypercholesterolaemia displayed a lower bone mineral density (BMD) and increased beta collagen cross­linking (beta­CTX) and type I anterior collagen amino terminal peptide (PINP) levels compared to those of the control subjects. Serum cholesterol levels were a significant independent predictor of BMD, beta­CTX and PINP and were negatively correlated with BMD and positively correlated with beta­CTX and PINP levels. Our animal experimental results validated our clinical results, as they also indicated that hypercholesterolaemia damages bone microstructure and reduces bone strength. Cholesterol directly increased osteoblast functional gene expression in vitro. Hypercholesterolaemia increases the risk of high­turnover osteoporosis in men at least in part by excessively promoting the activity of the remodelling pathway. In addition, hypercholesterolaemia damages the bone microstructure, resulting in osteopenia or OP and reduced bone strength, leading to a higher risk of fracture in men. We emphasize the importance of preventing and treating hypercholesterolaemia as well as monitoring bone metabolic markers and BMD in men with hypercholesterolemia for the effective prevention of bone loss and subsequent fracture. In addition, our findings provide a theoretical basis for the development of treatments for high cholesterol­induced osteoporosis in men.

Relationship between ancient bridges and population dynamics in the lower Yangtze River Basin, China.

It has been suggested that population growth dynamics may be revealed by the geographic distribution and the physical structure of ancient bridges. Yet, this relationship has not been empirically verified. In this study, we applied the archaeological records for ancient bridges to reveal the population growth dynamics in the lower Yangtze River Basin in late imperial China. We investigated 89 ancient bridges in Yixing that were built during the Ming and Qing dynasties (AD1368-1911). Global Position System information and structure (length, width, and span) of those bridges was measured during our field investigations. Their distribution density was calculated by ArcGIS. The historical socio-economic dynamics of Yixing was inferred from the distribution and structure of ancient bridges. Based on the above information, the population growth dynamics in Yixing was projected. Our results show that 77 bridges were built in Yixing during the Qing dynasty, which is 6.41 times more than the number built during the Ming dynasty. In the Ming dynasty, bridges were built on pivotal routes; in the Qing dynasty, bridges were scattered across various places. Over the period, the density distribution of bridges shifted northwestward, while the average length and width of bridges decreased. The increasing number of bridges corresponded to population growth, largely attributable to massive clan migration from northern China during the Little Ice Age. The shift in the density distribution of bridges corresponded to the formation of settlements of large clans and the blossoming of Yixing Teapot handicrafts. The scattering and the reduction in average length and width of bridges was due to the dispersal of population and the associated formation of small settlements in the latter period. Our approach is innovative and robust, and could be employed to recover long-term historical population growth dynamics in other parts of China.

Laparoscopic cholecystectomy in elderly patients: an evaluation of immunity.

OBJECTIVE: We sought to investigate the impact of laparoscopic cholecystectomy (LC) on the inflammatory response and immunological function of elderly patients compared with that on the younger ones. METHODS: Between June 2012 and June 2013, this prospective study investigated a total of 112 patients having the surgery of LC due to symptomatic cholelithiasis or polyps, among whom 52 were elderly patients with the age beyond 65 years old and the remaining 60 were younger than the age. Peripheral venous blood samples were taken from these patients prior to surgery and on post-operative days 1, 3 and 7, respectively. The perioperative clinical outcomes and immunological function results were analyzed and compared between the two groups divided by age. RESULTS: The demographics of the two groups did not differ except for the age. Surgical trauma seemed more serious for elderly patients as illustrated by the longer operating time, hospital stay and more quantity of patients got complication. Both groups indicated changes in inflammatory and immune aspects. Compared with the younger ones, elderly patients showed less quantity of preoperative basic immune cells, delayed immune responses after the surgical trauma of LC and hyporeactivity of inflammatory response when accepting LC. CONCLUSIONS: An examination of the inflammatory reaction and immune response after LC demonstrated that there are significant differences observed in two groups divided by age. Further studies with more samples are required to determine the exact relationship of perioperative immune change and higher adverse outcome rate of aged people.

Distribution of serum transferrin, and its associations with metabolic disorders among Chinese: A nation-wide, health and nutrition survey.

SCOPE: This study examined the associations of serum transferrin and metabolic disorders among Chinese population. METHODS AND RESULTS: This study is based on nation-wide, population-based China Health and Nutrition survey including 8564 men and women aged 18 years or older. Anthropometric and fasting blood glucose, insulin, lipids, and transferrin data were collected. Elevated transferrin concentrations associated with higher body mass index, waist circumference, lipids, insulin, glucose (all p < 0.0001). Serum transferrin concentrations increased gradually with increasing numbers of metabolic syndrome (MetS) components among men and women (p = 0.0003). Elevated concentrations of transferrin were significantly related with higher risk of MetS (p = 0.0006), obesity (p = 0.0089), overweight (p < 0.0001). No associations between transferrin concentrations and risk of diabetes and high blood pressure were observed in both men and women. CONCLUSION: Elevated transferrin concentrations were positively associated with risk of MetS and obesity, but not with risk of diabetes among Chinese.

The growing spectrum of anti-inflammatory interleukins and their potential roles in the development of sepsis.

Sepsis, recognized as a deadly immunological disorder, is one of the major causes of death in intensive care units globally. Traditionally, sepsis was characterized by an excessive systemic proinflammatory response to invasive microbial pathogens. However, failures of highly sophisticated trials directed toward the uncontrolled inflammatory reaction have led to an appeal by experts for reevaluation of the present approach toward sepsis. With accumulated evidence, a principal role for immunosuppression in severe sepsis has been evaluated. Different pathways of negative regulation in the pathophysiological process of sepsis have been investigated. Significant among these regulatory elements are the anti-inflammatory cytokines. In the past few years, several interleukins (ILs) have been identified and characterized, among which IL-35 and IL-37 represent newly identified ones in the spectrum of anti-inflammatory cytokines. In this study, we focus on regulatory cytokines of the IL family (including the old members: IL-4, IL-10, and IL-13, and newly discovered ones: IL-35 and IL-37) to address current knowledge regarding their structural and functional characteristics as well as their roles in the development of sepsis. Although the exact roles for these cytokines are pending further elucidation, the current advances in our understanding of mechanisms that regulate the immune responses during severe sepsis may lead to the identification of new diagnostic or treatment targets.

Roles of Tregs in development of hepatocellular carcinoma: a meta-analysis.

AIM: To assess systematically the association between regulatory T cells (Tregs) and hepatocellular carcinoma (HCC). METHODS: We searched Medline, Embase and Wanfang databases for literature on the populations of Tregs in HCC patients and controls, using the pooled OR and 95%CIs for assessment. There were no limitations with respect to publication date or language. The references of qualifying articles were also searched. We excluded studies with unclear data or overlapping studies. Twenty-three studies met our criteria, and the quality of these studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN). The meta-analysis of association between Tregs and HCC was undertaken using the random-effects approach, as described by DerSimonian and Laird. Subgroup analysis was performed when at least three studies were available. Potential publication bias was assessed by visual inspection of the funnel plot, and an asymmetric plot suggested possible publication bias. RESULTS: Twenty-three studies with a total of 1279 HCC patients and 547 healthy volunteers as controls were enrolled. The frequency of circulating Tregs in HCC patients was 87% higher than in healthy controls (OR = 1.87, 95%CI: 1.49-2.34). The frequency of Tregs in the HCC tumor microenvironment was significantly higher than that in tumor-surrounding tissue and biopsy specimens from healthy livers (OR = 4.04, 95%CI: 2.10-7.79, P = 0.000; OR = 2.869, 95%CI: 2.16-3.82, P = 0.000). However, subgroup analyses based on the different types of tumors or patient characteristics such as tumor size, tumor number or α fetoprotein (AFP) levels in HCC patients, showed that populations of Tregs as a whole were not significantly changed between groups (P > 0.05 for all). CONCLUSION: There is an obvious association between Tregs and pathogenesis of HCC. Further well-designed clinical studies are warranted to illustrate the potential role of Tregs in HCC.

Percutaneous radiofrequency ablation guided by contrast-enhanced ultrasound in treatment of metastatic hepatocellular carcinoma after liver transplantation.

This study evaluated the advantages and applications of contrast-enhanced ultrasound (CEUS)-supported percutaneous radiofrequency ablation (RFA) in the treatment of metastatic hepatocellular carcinoma after liver transplantation, based on clinical details. CEUS-supported percutaneous RFA was adopted to treat 12 patients with hepatic metastatic carcinomas after liver transplantation. The diameters of the metastatic carcinomas varied from 1 cm to 5 cm, and the foci were discovered after 3 months to 12 months. Each focus was diagnosed and localised by CEUS for RFA once or twice. Curative effects were evaluated by CEUS or contrast-enhanced CT after the treatment. The re-examination results at 2 weeks post-treatment showed that the foci of 11 patients were ablated completely, whereas one patient with the largest focus required retreatment by RFA because of a partial residue. No local recurrence was found one month later in the re-examination. CEUS-supported percutaneous RFA in the treatment of hepatic metastatic carcinoma after liver transplantation has the advantages of accurate localisation, good efficacy, easy operation, and minimal invasion without any complications. Therefore, it can be recommended as the preferred therapy for hepatic metastatic carcinoma after liver transplantation.