Regulatory effects of the AMPKα-SIRT1 molecular pathway on insulin resistance in PCOS mice: An in vitro and in vivo study.

In order to preliminarily explore the correlation between the AMPKα-SIRT1 pathway and insulin resistance and reproductive function in PCOS mice and find the pathogenesis molecular mechanism and potential therapeutic target of PCOS, we carried out in vitro study of human granulosa KGN cells and in vivo study of PCOS mouse model which was constructed with DHEA, and AICAR and Compound C were applied. We have found that SIRT1 and AMPKα expression in KGN cells gradually decreased as DHEA concentration increased; Mice of the PCOS model were in an obvious status of IR (P < 0.05). Granulosa cells in their ovarian were present in fewer numbers and were disorderly arranged, their numbers of immature follicles were significantly increased, and their AMPKα-SIRT1 pathways were down-regulated. The AMPKα-SIRT1 pathway could be up-regulated after AICAR treatment, resulting in improved IR status (P < 0.0001); however, the abovementioned effect was blocked by Compound C. Thus we concluded that the AMPKα-SIRT1 molecular pathway may be a molecular mechanism of IR in PCOS and may serve as a therapeutic target for the development of potential treatments for improving metabolic and reproductive function in PCOS.

Application of a specialist nurse-led multidisciplinary team model in the perioperative care of patients undergoing simultaneous pancreas and kidney transplantation: randomized controlled trial.

Background: Simultaneous pancreas and kidney transplantation (SPKT) is an effective treatment option for individuals who suffer from both diabetes mellitus and renal failure. However, experiments exploring nurse-led multidisciplinary team management during the perioperative management of patients undergoing SPKT are currently limited. This study aims to explore the clinical performance of a transplant nurse-led multidisciplinary team (MDT) in the perioperative management of SPKT patients. Methods: A total of 218 patients who underwent SPKT were randomly assigned to either a control group (n=116) receiving conventional care or an intervention group (n=102) managed through a transplant nurse-led MDT approach. The incidence of postoperative complications, hospital stay, total hospitalization cost, readmission rate, and postoperative nursing quality were compared between these 2 groups. Results: The intervention and control groups showed no significant differences in age, gender, and body mass index. Compared with the control group, the intervention group had a significantly lower incidence of postoperative pulmonary infection and gastrointestinal (GI) bleeding (27.6% vs. 14.7% and 31.0% vs. 15.7%, respectively, both P<0.05). Compared to the control group, the intervention group had significantly lower hospitalization costs, length of hospital stay, and readmission rate 30 days after discharge (32.98±9.10 vs. 36.78±15.36, 26.47±13.4 vs. 31.03±11.61 and 31.4% vs. 50.0%, respectively, all P<0.05). Additionally, the intervention group had significantly better quality of postoperative nursing care than the control group (11.61±0.69 vs. 9.64±1.42, P<0.01), the availability of infection control and prevention measures (11.74±0.61 vs. 10.53±1.11, P<0.01), the effectiveness of health education (11.73±0.61 vs. 10.41±1.06, P<0.01), the effectiveness of rehabilitation training (11.77±0.54 vs. 10.37±0.96, P<0.01), and the patient satisfaction with nursing care (11.83±0.42 vs. 10.81±1.08, P<0.01). Conclusions: The nurse-led MDT model for transplant patients can reduce complications, shorten hospital stays, and save costs. It also provides clear guidelines for nurses, improving care quality and aiding patient recovery. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900026543.

Blood unconjugated bilirubin and tacrolimus are negative predictors of specific cellular immunity in kidney transplant recipients after SAR-CoV-2 inactivated vaccination.

The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.

Nursing of acute graft-versus-host disease after simultaneous pancreas-kidney transplantation: a case series study.

Background: This paper aimed to summarize our experience in the nursing of acute graft-versus-host disease (aGVHD) after simultaneous pancreas-kidney transplantation (SPK). Methods: We retrospectively collected and analyzed the demographic characteristics, preoperative evaluation, donor evaluation, screening, and surgical methods of patients with aGVHD after SPK in our center from September 2016 to September 2019. Results: One patient developed intractable diarrhea with decline in platelet (PLT), white blood cell (WBC), and red blood cell (RBC) counts. Meanwhile, the other two patients experienced facial and trunk rashes, hepatic impairment, as well as decreased PLT, WBC, and RBC counts. We took the following nursing interventions: establishing an intensive care team and close monitoring of changes in the condition; protective isolation to minimize exogenous infections; nursing of pulmonary infections; and nutritional support. However, despite careful treatment and nursing, the conditions of the three patients subsequently worsened rapidly and became uncontrollable, and all died. Conclusions: aGVHD is extremely rare after SPK, and no literature exists concerning nursing care or management related to this condition. Clinical manifestations and histopathology are helpful for diagnosis; however, treatment outcomes might be unsatisfactory and the prognosis is poor. Early detection, diagnosis, and intervention have a positive impact on the prognosis of aGVHD, and proper nursing can benefit patients.

Effects of Long Noncoding RNA HOXA-AS2 on the Proliferation and Migration of Gallbladder Cancer Cells.

To explore the function and mechanism of lncRNA HOXA-AS2 in cancer-associated fibroblasts (CAFs)-derived exosomes in gallbladder cancer metastasis, and provide new research targets for the treatment of gallbladder cancer. At the same time, in order to clarify the early predictive value of lncRNA HOXA-AS2 for gallbladder cancer metastasis, and to provide a theoretical basis for clinical individualized treatment of gallbladder cancer. Methods. In our previous work, we used TCGA database analysis to find that lncRNA HOXA-AS2 was highly expressed in gallbladder cancer tissues compared with normal tissues. In this study, the expression levels of HOXA-AS2 in gallbladder cancer cell lines and control cells were first verified by QPCR and Western blot methods. Then, lentiviral tools were used to construct knockdown vectors (RNAi#1, RNAi#2) and negative control vectors targeting two different sites of HOXA-AS2, and the vectors were transfected into NOZ and OCUG-1 cells, respectively. Real-time PCR was used to detect knockdown efficiency. Then, the effects of silencing HOXA-AS2 on the proliferation, cell viability, cell migration, and invasion ability of gallbladder cancer cells were detected by MTT, plate cloning assay, Transwell migration chamber assay, and Transwell invasion chamber assay. Finally, the interaction between HOXA-AS2 and miR-6867 and the 3'UTR of YAP1 protein was detected by luciferase reporter gene. The results showed that the expression level of HOXA-AS2 in gallbladder cancer cell lines was higher than that in control cells. The expression of HOXA-AS2 in gallbladder carcinoma tissues was significantly higher than that in adjacent tissues (p < 0.05). After successful knockout of HOXA-AS2 by lentiviral transfection, the expression of HOXA-AS2 in gallbladder cancer cell lines was significantly decreased. Through cell proliferation and plate clone detection, it was found that silencing HOXA-AS2 inhibited cell proliferation and invasion. Through software prediction and fluorescein reporter gene detection, it was found that HOXA-AS2 has a binding site with miR-6867, and the two are negatively correlated, that is, the expression of miR-6867 is enhanced after the expression of HOXA-AS2 is downregulated. And the 3'UTR of YAP1 protein in the Hippo signaling pathway binds to miR-6867. Therefore, HOXA-AS2 may affect the expression of YAP1 protein by regulating miR-6867, thereby inhibiting the Hippo signaling pathway and promoting the proliferation and metastasis of gallbladder cancer cells. HOXA-AS2 is abnormally expressed in gallbladder cancer cells. HOXA-AS2 may promote the migration and invasion of gallbladder cancer cells by regulating the Hippo signaling pathway through miR-6867. HOXA-AS2 may serve as a potential diagnostic and therapeutic target for gallbladder cancer in clinic.

Clinical features of multidrug-resistant organism infections in early postoperative solid organ transplantation in a single center.

BACKGROUND: The increasing occurrence of multidrug-resistant organisms (MDROs) infections has posed major challenge to solid organ transplantation (SOT). For SOT recipients, high-dose immunosuppressants and broad-spectrum antibiotics can markedly increase the risk of early postoperative MDRO infections and thus have adverse effects on the outcomes of SOT. Here, we analyzed the incidence and clinical features of early MDRO infections after SOT, in an attempt to provide new evidence for the control and treatment of early MDROs. METHODS: The clinical data of 133 patients with MDRO infections after SOT in our department from 2017 to 2020 were retrospectively collected, and clinical features including incidence, etiologies, infection sites, and complications, were analyzed. RESULTS: The incidence of MDRO infections after SOT was 9.9%. Simultaneous liver and kidney transplantation patients had the highest incidence of MDRO infections, followed by the recipients of liver transplantation and simultaneous pancreas-kidney transplantation; patients undergoing renal transplantation had the lowest incidence of MDRO infections. The most common pathogen was extended spectrum beta-lactamase (ESBL)-producing organisms (n=88, 66.2%), the most common infection site was the urinary system (n=58, 43.6%), and the main postoperative complications were urinary tract infections (n=44, 33.1%) and lung infections (n=41, 30.8%). MDRO infections were cured in most cases. CONCLUSIONS: A sound knowledge of the clinical features of MDRO infection after SOT is important for the successful prevention and treatment of these infections.

Construction and reliability and validity tests of the dietary self-management ability scale for kidney transplant recipients.

BACKGROUND: To establish a dietary self-management evaluation indicators scale for kidney transplant recipients and to test the reliability and validity of the scale. METHODS: Based on the knowledge attitude practice model (KAP model) of health-related behavior changes, an evaluation indicators scale of dietary self-management ability of kidney transplant recipients was constructed through a literature review, expert consultation and group discussion. A questionnaire survey was carried out with 102 kidney transplant recipients from a large tertiary hospital to test the reliability and validity of the constructed scale. RESULTS: The dietary self-management ability scale for kidney transplant recipients had 29 items in 3 dimensions. The content validity at the scale level was 0.969, and the content validity at the item level was 0.778-1.000. Exploratory factor analysis extracted 3 common factors, and the cumulative variance contribution rate was 68.610%; the correlation coefficient between each dimension was 0.467-0.629, and the correlation coefficient between each dimension and the total score of the scale was 0.648-0.845. Cronbach's α for the scale was 0.831, and the test-retest reliability of the scale was 0.910. CONCLUSIONS: The constructed dietary self-management ability scale for kidney transplant recipients has good reliability and validity and can be used as a tool to evaluate the dietary self-management ability of kidney transplant recipients.

Effects of metformin and Exenatide on insulin resistance and AMPKα-SIRT1 molecular pathway in PCOS rats.

AIMS: This study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms. METHODS: An in vitro PCOS model was established by DHEA (6 mg/(100 g•d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg•d) daily. The EX group was subcutaneously injected EX 10µg/(kg•d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPKα and SIRT1 in the ovaries of each group. RESULTS: After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05). CONCLUSIONS: Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.

Associations of hormonal contraceptives and infertility medications on the risk of venous thromboembolism, ischemic stroke, and cardiovascular disease in women.

The purpose of this study was to examine the relations of hormonal contraceptives and infertility drugs with the risk of venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and cardiovascular disease. The Taiwan National Health Institute Research Database was searched for women who had taken hormonal contraceptives or infertility medications from 2000 to 2010. The two groups were age and index date matched with controls (1:4 ratios). Cox regression analysis was used to examine the risks of VTE, DTE, PE, ischemic stroke, and cardiovascular disease. A total of 32,067 women were included in the hormonal contraceptives group and 4710 in the infertility medications group (matched controls: 127,872 and 18,840, respectively). After adjustment for age, comorbidities, and other confounders, the contraceptives group had a higher risk of VTE (adjusted HR 1.14, 95% CI 1.004 to 1.30) and cardiovascular disease (adjusted HR 1.30, 95% CI 1.26 to 1.34), and lower risk of ischemic stroke (adjusted HR 0.90, 95% CI 0.86 to 0.95). The infertility medications group had a higher risk of VTE (adjusted HR 1.996, 95% CI 1.41 to 2.72) and DVT (adjusted HR 1.86, 95% CI 1.31 to 2.63), and lower risk of ischemic stroke (adjusted HR 0.82, 95% CI 0.68 to 0.99) and cardiovascular disease (adjusted HR 0.83, 95% CI 0.74 to 0.94). Hormonal contraceptives and infertility medications appear to lower the risk of ischemic stroke and increase the risk of VTE; however, their effect on the risk of other types of cardiovascular events varies.