Objective Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. Methods In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. Results The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found. Conclusion The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.
Objective
To identify the cause and its pathogenic mechanism in one case with permanent neonatal diabetes mellitus(PNDM).
Methods
One case of PNDM diagnosed in Peking Union Medical College Hospital was analyzed for clinical features. Genomic DNA was extracted, followed by amplification with polymerase chain reaction and direct sequencing of glucokinase (GCK) gene. Wild and mutant plasmids were constructed and then expressed in E.coli. The recombinant proteins were purified, then tested to clarify their enzyme kinetics and thermal stability. Data between two groups were analyzed by t test.
Results
Compound heterozygous mutation c.571 C>T(R191W) and c.1136 C>A(A379E) in GCK gene were detected in this child. Compared with the wild type, mutants R191W and A379E had lower protein yield ((86±9) vs (48±8) mg/L;(86±9) vs (54±5) mg/L; t=5.56, 5.36, both P<0.01), lower appetency for glucose(the half-saturating substrate concentration (S0.5) for glucose:(7.63±0.21) vs (35.27±2.20)mmol/L; (7.63±0.21) vs (13.30±0.44)mmol/L, t=-21.70, -20.32, both P<0.01), lower appetency for ATP(Km: (0.30±0.01) vs (0.42± 0.01) mmol/L; (0.30±0.01) vs (0.54±0.04) mmol/L, t=-17.02,-10.68, both P<0.01) and lower catalytic ability ((20.9±2.1)/s vs (6.5 ± 1.0)/s; (20.9±2.1)/s vs (10.5 ± 1.1)/s; t=10.61, 7.58, both P<0.01). The both mutants also showed increased thermal instability.
Conclusion
Compound heterozygous mutations R191W and A379E in GCK gene promote the development of PNDM by affecting enzyme kinetics of glucokinase as well as lowering protein stability.
Key words:
Permanent neonatal diabetes mellitus; Glucokinase; Gene mutation; Enzyme kinetics
An increased risk of cardiovascular and metabolic diseases (CVMDs) among patients with cancer suggests a potential link between CVMD and cancer. The impact of CVMD on the survival time of patients with esophageal and gastric cancer remains unknown. We aimed to determine the incidence of CVMD and its impact on the longterm outcomes in esophageal and gastric cancer patients.A total of 2074 cancer patients were enrolled from January 1, 2007 to December 31, 2017 in two hospitals, including 1205 cases of esophageal cancer and 869 cases of gastric cancer, who were followed up for a median of 79.8 and 79.3 months, respectively. Survival time was analyzed using the Kaplan-Meier method before and after propensity score matching.The incidence of CVMD in patients with esophageal and gastric cancer was 34.1% (411/1205) and 34.3% (298/869), respectively. The effects of hypertension, diabetes, and stroke on the long-term survival of esophageal and gastric cancer patients were not significant (all P > 0.05). The survival time was significantly longer in esophageal cancer patients without ischemic heart disease than in patients with ischemic heart disease, both before matching (36.5 vs. 29.1 months, P = 0.027) and after matching (37.4 vs. 27.9 months, P = 0.011). The survival time in gastric cancer patients without ischemic heart disease was significantly longer than in patients with ischemic heart disease, both before (28.4 vs.17.5 months, P = 0.032) and after matching (29.5 vs.17.5 months, P = 0.02).The survival time of esophageal and gastric cancer patients with ischemic heart disease was significantly reduced compared to that of esophageal and gastric cancer patients without ischemic heart disease.
Objective
To summarize the nursing care of one case of Sheehan syndrome with huge four stages of stress injury.
Methods
For 1 case Sheehan syndrome with huge four stages pressure ulcers, on local wound, dynamically adjust the treatment plan according to the wound assessment situation, and by applying the theory of PDCA and wet healing throughout. At the same time, observation patient's condition carefully and supervision of drug effect, the implementation of specialized subject catheter nursing, nutritional support, overall nursing measures, such as vacuum treatment and psychological intervention and after discharge to special care and guidance were performed.
Results
The patient was discharged from the hospital 115 d and healed 336 d.
Conclusions
The nursing and treatment for the patient with Sheehan syndrome with huge four stages of stress injury can consolidate the basic knowledge of nursing staff, improve nursing skills, increase nursing dressing technology, provide a theoretical basis and practical experience for clinical nursing work.
Key words:
Sheehan syndrome; Pressure injury
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract Cyclophosphamide (CP) is a clinical anticancer drug that can cause male reproductive abnormalities, but the underlying mechanisms for this remain unknown. The present study aimed to explore the potential toxicity induced by CP in spermatogenesis events of germ cell proliferation, meiosis, and blood‐testis barrier integrity at the molecular level. CP‐treated mice showed significantly reduced serum testosterone levels, sperm motility and concentration. The results of immunohistochemistry and Western blot showed that CP reduced the proliferation of germ cells (PCNA, PLZF) and increased germ cell apoptosis (Bax and TUNEL‐positive cells) in CP‐treated mice testes. The expression of meiotic related proteins (SYCP3, REC8, MLH1) decreased significantly in the fourth week after administration, and the expression of blood‐testis barrier related proteins (β‐catenin, ZO‐1) and sperm quality‐associated proteins (PGK2, HSPA4) decreased significantly in the first week after administration. CP leads to the apoptosis of male germ cells, inhibits the proliferation of germ cells, and affects meiosis and the blood‐testis barrier, resulting in the decline of sperm quality. This study provides information to further the study of molecular mechanism and protective strategy of CP influence.
Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet) or a low chromium diet (LC, 0.14 mg chromium/kg diet) during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON), while others remained on the same diet (CON-CON, or LC-LC) for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA methylation which is associated with the insulin signaling pathway in the mice livers.
Introduction: Non-statin cholesterol-lowering therapies (proprotein convertase subtilisin/kexin type 9 monoclonal antibodies [PCSK9mAb] and ezetimibe) have been shown to reduce atherosclerotic cardiovascular disease (ASCVD) events in randomized clinical trials of patients treated with statin therapy. Effectiveness in the real world, however, is contingent on treatment persistence and adherence. Aim: To estimate the proportion of patients who were on therapy, persistent and had high adherence at 365 days following the initiation of a PCSK9mAb versus ezetimibe in real-world clinical practice. Methods: We included adults initiating a PCSK9mAb (n= 16,588, 44% ≥ 65 years, 56% male, 78% with ASCVD) or ezetimibe (n=83,086, 35% ≥ 65 years, 51% male, 46% with ASCVD) from Medicare and MarketScan commercial health insurance databases between 7/2015 and 12/2019. We assessed 3 outcomes using pharmacy claims within 365 days following initiation (assessment period): 1) percentage of patients on therapy: percentage of patients with medication supply in the last 60 of 365 days following initiation; 2) persistence: not having a gap of ≥ 60 days between the last day of supply from one pharmacy claim and the next claim; 3) high adherence: having a day of supply for ≥ 80% of the 365 days. Results: Percentage on therapy, persistence, and high adherence were higher among patients on PCSK9mAb versus ezetimibe at 365 days (Table 1). When, restricted to participants who were persistent at 365 days, adherence to both PCSK9mAb and ezetimibe was high. The adjusted multivariable-adjusted risk ratio [95% CI] for percentage on therapy, persistent and having high adherence to PCSK9mAb versus ezetimibe was: 1.20 [1.18, 1.21], 1.22 [1.20, 1.24], and 1.16 [1.14, 1.18]. Conclusions: Patients initiating PCSK9mAb were more likely to be on therapy, persistent and with high adherence at 365 days compared to their counterparts who initiated ezetimibe. Funding: Amgen Inc.
Berberine is known to improve glucose and lipid metabolism disorders, but it poorly absorbed into the blood stream from the gut. Therefore, the exact underlying mechanism for berberine is still unknown. In this study, we investigated the effect of berberine on glucose metabolism in diabetic rats and tested the hypothesis that berberine acts directly in the terminal ileums.Rats were divided into a control group, diabetic group (DM), low dose of berberine group (BerL) and high dose of berberine group (BerH). Ileum samples were analyzed using a Roche NimbleGen mRNA array, qPCR and immunohistochemistry.We found that 8 weeks of treatment with berberine significantly decreased fasting blood glucose levels. An oral glucose tolerance test (OGTT) showed that blood glucose was significantly reduced in the BerL and BerH groups before and at 30 min, 60 min and 120 min after oral glucose administration. Plasma postprandial glucagon-like peptide-1 (GLP-1) levels were increased in the berberine-treated groups. The ileum from the BerH group had 2112 genes with significantly changed expression (780 increased, 1332 decreased). KEGG pathway analyses indicated that all differentially expressed genes included 9 KEGG pathways. The top two pathways were the MAPK signaling pathway and the GnRH signaling pathway. Q-RT-PCR and immunohistochemistry verified that glucagon-like peptide 1 receptor (Glp1r) and mitogen activated protein kinase 10 (Mapk10) were significantly up-regulated, in contrast, gonadotropin releasing hormone receptor (Gnrhr) and gonadotropin-releasing hormone 1 (Gnrh1) were down-regulated in the BerH group.Our data suggest that berberine can improve blood glucose levels in diabetic rats. The mechanisms involved may be in the MAPK and GnRh-Glp-1 pathways in the ileum.
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