Application of improved glomerular filtration rate estimation by a neural network model in patients with neurogenic lower urinary tract dysfunction.

BACKGROUND: Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. OBJECTIVE: To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. DESIGN: Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. PATIENTS: A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. METHODS: The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. RESULTS: The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). CONCLUSION: The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Creatinine-based equations to estimate glomerular filtration rate should be used with caution in patients with neurogenic bladder.

BACKGROUND: Patients with neurogenic bladder (NGB) are at an increased risk of developing chronic kidney disease (CKD). However, data related to the real performance of the serum creatinine (Cr)-based estimated glomerular filtration rate (eGFR) equation in patients with NGB are limited. This study is to evaluate the performance of new Cr-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without race and the GFR estimation equation for Chinese CKD patients for the estimation of GFR in Chinese patients with NGB. MATERIALS AND METHODS: GFR was determined simultaneously by three methods: a) GFR measured by renal dynamic imaging with 99mTc-DTPA (G-GFR), which was used as the reference GFR; b) GFR estimated by the new Cr-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without race (EPI-GFR); and c) GFR estimated by the equation for Chinese CKD patients (C-GFR). Pearson correlation and linear regression were used to compare eGFR and G-GFR. Differences, absolute differences, precision, and accuracy were compared to identify which equation showed better performance in evaluating GFR in patients with NGB. RESULTS: A total of 171 patients with NGB, including 121 men and 50 women from 20 provinces, 4 autonomous regions, and 3 municipalities in China, were enrolled in the final analysis, and the average age was 31.3 ± 11.9 years. Both C-GFR and EPI-GFR were moderately correlated with G-GFR and overestimated G-GFR. The difference between EPI-GFR and G-GFR was similar to that between C-GFR and G-GFR (median of 9.97 vs. 9.95 mL/min/1.73m2 for difference, Wilcoxon signed ranks test, Z = -1.704, p = 0.088), but the absolute difference between EPI-GFR and G-GFR was significantly lower than that between C-GFR and G-GFR (median of 22.3 vs. 25.1 mL/min/1.73m2 for absolute difference, Wilcoxon signed ranks test, Z = -4.806, p < 0.001). Both EPI-GFR and C-GFR displayed similar results of 15, 30, and 50% accuracies (χ2-test, p > 0.05), and there were no significant differences between EPI-GFR and C-GFR in misclassification percentages at different G-GFR levels (χ2-test, p > 0.05). CONCLUSION: Our study indicated that for patients with NGB in China, Cr-based eGFR equations, which include the new CKD-EPI equation without race and the Chinese GFR estimation equation, showed suboptimal performance, and limited their application in GFR estimation. Further studies are needed to investigate whether incorporating additional biomarkers, such as cystatin C, could improve their performance of GFR estimating equations in patients with NGB.

Clinical characteristics and management of hemodialysis patients with pre-dialysis hypertension: a multicenter observational study.

BACKGROUND: Hypertension is a leading preventable risk factor for cardiovascular disease in hemodialysis patients. Pre-dialysis systolic blood pressure (SBP) more than 160 mmHg was thought to be associated with increased risk of cardiovascular events and all-cause mortality. The present study was performed to explore the clinical characteristics and management of hemodialysis patients with pre-dialysis SBP ≥ 160 mmHg. METHODS: A total of 1233 patients undergoing hemodialysis from nine hemodialysis centers were enrolled. Pre-dialysis and home BP were measured and clinical data were collected. The characteristics of patients with pre-dialysis SBP ≥ 160 mmHg were explored. Clinical parameters between hypertensive and non-hypertensive patients were compared. The partial correlation analyses performed to identify the associations between BP and clinical parameters. RESULTS: There were 24.6% of the hemodialysis patients had pre-dialysis SBP ≥ 160 mmHg and the average SBP was 173.8 ± 10.9 mmHg. Only 21.4% of the patients achieved dry weight after dialysis and up to 30.2% of patients were not given combination therapies of antihypertensive drugs. Compared to patients with pre-hemodialysis SBP < 160 mmHg, patients with pre-dialysis SBP ≥ 160 mmHg had lower target-reaching rate of Kt/v and higher incidences of intradialytic hypotension and muscle spasm. Most patients (96%) with pre-dialysis SBP ≥ 160 mmHg had home SBP≥ 135 mmHg. Patients with home SBP ≥ 160 mmHg had higher left ventricular weight index and lower hemoglobin levels when compared to their counterparts with home SBP <160 mmHg. CONCLUSIONS: Pre-dialysis SBP ≥ 160 mmHg is common in clinical practice and most of the patients could diagnosed to be hypertensive according to their home SBP. Patients with pre-dialysis SBP ≥ 160 mmHg are more likely to be subjected to dialysis insufficiency and intradialytic complications. Achieving dry weight and sufficient pharmacologic interventions should be strengthened to improve BP control in the hemodialysis population.

Laparoscopic Single-site "In-bag" Ovarian Dermoid Cystectomy in a 16-week- pregnant Patient.

STUDY OBJECTIVE: To demonstrate a novel "in-bag" ovarian cystectomy technique for a large adnexal mass in pregnancy. DESIGN: Stepwise demonstration with narrated video. SETTING: An academic tertiary care hospital. The patient was a 26-year-old woman, gravida 1, para 0, at gestational age of 7 weeks and 3 days who presented to the emergency department with persistent left pelvic pain and was diagnosed with a 16 cm × 10 cm × 12 cm dermoid cyst. She re-presented at gestational age of 16 weeks and 3 days with worsening pelvic pain, and the decision was made to proceed with surgical intervention. INTERVENTIONS: Laparoscopic transumbilical single-site surgery for the surgical management of adnexal masses in pregnancy has been demonstrated to be feasible and safe [1-3]. However, single-site laparoscopic ovarian cystectomy can be very challenging in pregnancy, especially when the need for suturing arises. Exteriorizing the ovary and cyst after intraperitoneal drainage may allow for extracorporeal suturing that is faster and easier; however, it may increase the probability of spillage of cystic contents if it is not performed in a bag, which can then cause peritonitis in cases of dermoid cysts. A combination of in-bag and extracorporeal ovarian cystectomy is a novel alternative minimally invasive approach that is cosmetic, safe, and effective. Several helpful techniques in this novel combination technique include the following: • Creating an umbilical incision of at least 2 cm or one that is large enough for better manipulation of both the surgical bag and adnexal mass. • Tightening the bag appropriately around the infundibulopelvic ligament so that it is not too tight leading to compromised blood supply and tissue necrosis, yet not too loose resulting in leakage of cystic contents. • Ensuring that the infundibulopelvic ligament is stabilized within the surgical bag. • Inserting small-sized wound retractor into the bag for better exposure during cystectomy. • Having a double-suction irrigation setup for large adnexal masses, as demonstrated in this patient, to reduce the spillage of cystic contents. The procedure was successfully performed in approximately 110 minutes, and the fetal heart rate postprocedure was 128 bpm through bedside transabdominal ultrasound. Estimated blood loss was 5 mL, and the patient was discharged the same day with an uneventful 4-week postoperative follow-up. CONCLUSION: Laparoscopic single-site "in-bag" ovarian dermoid cystectomy is feasible, effective, and safe in pregnant patients with a large adnexal mass. This technique results in better stabilization of the ovarian cyst and reduction of cystic content spillage.

Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal disease among female genital malignant tumors. Peptidylarginine deiminase type II(PADI II) has been shown to enhance a variety of cancers carcinogenesis, including ovarian cancer. The purpose of this study was to investigate the biological role of PADI2 in ovarian cancer (OC) and the relative mechanism. METHODS: Gene Expression Profiling Interactive Analysis (GEPIA) ( https://gepia.pku.cn/ ) and ONCOMINE ( https://www.oncomine.org/ ) were used to analyze PADI2 Gene Expression data. The survival curve for the PADI2 gene was generated by using the online Kaplan-Meier mapping site ( https://www.kmplot.com/ ). We conducted MTT assay, cloning formation assay and EdU cell proliferation assay to detect the cell activity of PADI2 knockdown A2780 and SKOV3 ovarian cancer cells treated with Olaparib. Cell migration and invasion were observed by would healing and transwell assay. The pathway changes after the treatment of PADI2 were detected by transcriptome sequencing and western blot. The role of PADI2 combined with Olaparib treatment in vivo was studied in nude mouse model bearing ovarian cancer tumor. RESULTS: We investigated the role of PADI2 on EOC in vitro and in vivo. PADI2 was upregulated in ovarian cancer samples and high PADI2 expression was correlated with poor outcome. Downregulating PADI2 suppressed colony formation, proliferation, migration and invasion of A2780 and SKOV3 cells. Furthermore, downregulating PADI2 and Olaparib combination treatment attenuated the viability, migration and invasion of A2780 and SKOV3 cells. We identified differentially expressed genes in A2780-shPADI2 and SKOV3-shPADI2 cell by transcriptome sequencing analysis and verified that downregulating PADI2 and Olaparib combination treatment suppresses EMT and JAK2/STAT3 signaling pathway in A2780 and SKOV3 cells in vitro and in vivo. CONCLUSIONS: Downregulation of PADI2 and Olaparib combination treatment attenuated the proliferation, migration and invasion of A2780 and SKOV3 cells by inhibiting the EMT through JAK2/STAT3 signaling pathway.

Effect of Intradialytic Exercise on Physical Performance and Cardiovascular Risk Factors in Patients Receiving Maintenance Hemodialysis: A Pilot and Feasibility Study.

INTRODUCTION: Although intradialytic exercise is considered a form of "nonpharmacological medicine" for patients receiving maintenance hemodialysis (MHD), this practice has not been widely implemented in most dialysis centers because of clinical limitations. We, therefore, aimed to design an intradialytic exercise training program to improve the implementation of this practice and determine its impact on physical performance and cardiovascular risk factors in patients receiving MHD. METHODS: A total of 132 MHD patients at 4 outpatient dialysis units were enrolled and assigned randomly into exercise (n = 67) and control groups (n = 65). During a 2-year period, patients in the exercise group participated in 20-min exercise training sessions within dialysis sessions on 3 days per week. All patients underwent assessments of physical function (6-min walk test) and cardiovascular risk factors (blood pressure [BP], total cholesterol [TC], low-density lipoprotein [LDL], high-sensitivity C-reactive protein [hsCRP], albumin [Alb], hemoglobin [Hb], and erythropoietin [EPO] dose) at the baseline and annually thereafter. RESULTS: Of the participants, 50.8% had completed the study after 2 years. No statistically significant intragroup or intergroup differences were observed in the measures of 6MD, BP, TC, hsCRP, Alb, Hb, and EPO dose. CONCLUSION: The results suggest that although this low-intensity, nonprogressive intradialytic exercise program may be practical, it was not sufficient to improve physiological function and reduce cardiovascular disease risk factors in patients receiving MHD.

The effect of BCM guided dry weight assessment on short-term survival in Chinese hemodialysis patients : Primary results of a randomized trial - BOdy COmposition MOnitor (BOCOMO) study.

BACKGROUND: Lack of accurate and effective assessment tools of fluid status is one of the major challenges to reach proper dry weight (DW) in chronic hemodialysis (HD) population. The aim of this randomized study was to evaluate the effect of bioimpedance guided DW assessment on long-term outcomes in Chinese HD patients. Eligible patients were randomly assigned (1:1) to two groups in each center, the control group and body composition monitor (BCM) group. In the BCM group, DW has been evaluated by bioimpedance technic every 2 months during follow-up. The primary composite endpoint consisted of death, acute myocardial infarction, cerebral infarction, cerebral hemorrhage, and peripheral vascular disease. METHODS: A total of 445 patients were recruited from 11 hemodialysis centers from Beijing, Tianjin and Shijiazhuang cities from Jan 1, 2013 to Dec 31, 2014. They were randomized into either BCM group or control group. All patients have been followed up for 1 year or until Dec 31, 2014 or censoring. RESULTS: At baseline, there were no significant differences between two groups in terms of demographic parameters, dialysis vintage, percentage of vascular access, and comorbid conditions. At the end of the study, 18 (4.04%) patients had died (11 in control group and 7 in BCM group). Kaplan-Meier survival analysis showed no significant difference in survival rates between two groups (log-rank test P = 0.07). However, there was an increasing trend of survival rates in BCM group compared to the control group. In the multivariable Cox analysis, there was a nonsignificant trend toward less primary composite end points in the BCM group in the adjusted analysis, the hazard ratio was impressive (0.487, 95% CI 0.217-1.091, P = 0.08). CONCLUSION: Bioimpedance technic has been applied to assess fluid status for decades and has been proved to be a promising tool for clinical practice. Although short-term outcomes were not improved in the randomized, controlled trial, the ascending trend in survival has been observed. Further studies are needed to investigate the survival benefit of bioimpedance method in DW assessment in a larger sample with longer follow-up period. TRIAL REGISTRATION: ClinicalTrials.org, NCT01509937. Registered 13 January 2012.

MiR-26a promotes apoptosis of porcine granulosa cells by targeting the 3ß-hydroxysteroid-Δ24-reductase gene.

OBJECTIVE: Apoptosis of ovarian granulosa cells (GCs) affects mammalian follicular development and fecundity. This study aimed to explore the regulatory relationship between microRNA-26a (miR-26a) and the 3ß-hydroxysteroid-Δ24-reductase gene (DHCR24) gene in porcine follicular granular cells (pGCs), and to provide empirical data for the development of methods to improve the reproductive capacity of pigs. METHODS: The pGCs were transfected with miR-26a mimic, miR-26a inhibitor and DHCR24-siRNA in vitro. The cell apoptosis rate of pGCs was detected by the flow cytometry. The secretion levels of estradiol (E2) and progesterone (P) in pGCs were detected by enzymelinked immunosorbent assay. Double luciferase validation system was used to detect the binding sites between miR-26a and DHCR24 3'-UTR region. Qualitative real-time polymerase chain reaction and Western blotting were used to verify the DHCR24 mRNA and protein expression in pGCs, respectively, after transfecting with miR-26a mimic and miR-26a inhibitor. RESULTS: Results showed that enhancement of miR-26a promoted apoptosis, and inhibited E2 and P secretion in pGCs. Meanwhile, inhibition of DHCR24 also upregulated the Caspase-3 expression, reduced the BCL-2 expression, promoted pGCs apoptosis, and inhibited E2 and P secretion in pGCs. There were the binding sites of miR-26a located within DHCR24 3'-UTR. Up-regulation of miR-26a inhibited DHCR24 mRNA and protein expression in pGCs. CONCLUSION: This study demonstrates that miR-26a can promote cell apoptosis and inhibit E2 and P secretion by inhibiting the expression of DHCR24 in pGCs.

Combined microRNAome and transcriptome analysis of follicular phase and luteal phase in porcine ovaries.

The aim of this study was to explore the expression difference of miRNAs and mRNAs between the follicular phase (FP) and luteal phase (LP) in porcine ovaries and provide a theoretical basis for the research on mammalian reproductive regulation. RNA-Seq and miRNA-Seq were used to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between the FP and LP in ovaries of six sows (3-year-old Yorkshire pigs with similar weights and same parities). Bioinformatic analysis was used to screen potential genes and miRNAs related to porcine ovarian function. Real-time qualitative PCR was used to validate the sequencing results. RNA-Seq results showed that 3,078 genes were up-regulated, and 1,444 genes were down-regulated in the LP compared with the FP, and DEGs were significantly enriched in 242 Gene Ontology (GO) terms and 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. miRNA-Seq identified 112 DEMs, of which 25 were up-regulated and 87 were down-regulated in the LP compared with the FP. We obtained 186 intersection genes (IGs) between the 4,522 DEGs and 2,444 target genes predicted from the 112 DEMs. After constructing a miRNA-gene-pathway network, we identified key miRNAs and genes including miR-17-3p, miR-214, miR-221-5p, miR-125b, FGF1, YWHAG, YWHAZ, FDFT1 and DHCR24, which are enriched in Hippo and PI3K-Akt signalling pathways, and various metabolic pathways. These results indicate that these key genes and miRNAs may play important roles in the developmental transition from FP to LP in porcine ovaries and represent candidate targets for further study.

Leptin/OB-R signaling is elevated in mice with Sjögren's syndrome and is implicated in disease pathogenesis.

Sjögren's syndrome (SjS) is a systemic autoimmune disease resulting in a severe dry mouth and dry eyes. Currently, care for patients with SjS is palliative, as no established therapeutics target the disease directly, and its pathogenetic mechanisms are uncertain. Leptin activates B cells to induce the secretion of proinflammatory and anti-inflammatory cytokines and is elevated in several autoimmune diseases. In this study, we found the expression of leptin and its receptor OB-R in mouse models of SjS are elevated both locally and systemically during SjS progression. Recombinant serotype 2 adeno-associated viral (rAAV2) vectors expressing either OB-R shRNA (rAAV2-shOB-R) or none (rAAV2-null) were injected into 4 or 16 week-old BALB/c NOD/LtJ (NOD) mice and resulted in a modest reduction in glandular inflammation in the SjS model. In conclusion, Leptin/OB-R signaling may be pathogenically involved in SjS and may serve as a new marker and a potential therapeutic target.

Robotic Single-Site Sacrocolpopexy Using Barbed Suture Anchoring and Peritoneal Tunneling Technique: Tips and Tricks.

STUDY OBJECTIVE: To demonstrate the tips and tricks of a simpler technique for single-site sacrocolpopexy using barbed suture anchoring and retroperitoneal tunneling to make the procedure more efficient and reproducible. DESIGN: Step-by-step description of surgical tutorial using a narrated video (Canadian Task Force classification III). SETTING: Academic tertiary care hospital. PATIENTS: Patient with Stage III uterine prolapse. INTERVENTIONS: Sacrocolpopexy is increasing utilized since the FDA warning about complications of vaginal mesh surgery. It is the gold standard for repair of apical prolapse. However, there is great variation in the sacrocolpopexy procedure techniques and they have not been standardized. Traditional single-site laparoscopic sacrocolpopexy is very challenging as the procedure time is long and suturing is difficult. The advantages of suturing with wristed needle drivers in robotic single-site surgery simplify this complex procedure. Furthermore, using barbed suture anchoring and peritoneal tunneling technique potentially decreases the surgeon's learning curve and makes the procedure reproducible. In this video, we demonstrate a supracervial hysterectomy with a stepwise explanation of the correct technique for performing a robotic single incision sacrocolpopexy. MEASUREMENTS AND MAIN RESULTS: Sacrocolpopexy is increasing used since the US Food and Drug Administration warning about complications of vaginal mesh surgery. It is the gold standard for repair of apical prolapse. However, a great variation exists in the sacrocolpopexy procedure techniques that need to be standardized. Traditional single-site laparoscopic sacrocolpopexy is very challenging because the procedure time is long and suturing is difficult. The advantages of suturing with wristed needle drivers in robotic single-site surgery simplify this complex procedure. Furthermore, using the barbed suture anchoring and peritoneal tunneling technique potentially decreases the surgeon's learning curve and makes the procedure reproducible. In this video, we demonstrate a supracervical hysterectomy with a stepwise explaation of the correct technique for performing a robotic single-incision sacrocolpopexy. CONCLUSION: The possibility of using the barbed suture and peritoneal tunneling technique with wristed needle drivers in robotic single-site sacrocolpopexy offers the possibility of an effective, safe, reproducible, and cosmetic surgical option.

Overexpression of GOLPH3 protein is associated with worse prognosis in patients with epithelial ovarian cancer.

Golgi phosphoprotein 3 (GOLPH3) has important roles in the pathogenesis of cancer, and overexpression of GOLPH3 has been found in several kinds of cancers. However, the relationship between GOLPH3 overexpression and prognosis in patients with epithelial ovarian cancer remains unknown. This study aimed to investigate the relationship between GOLPH3 overexpression and overall survival in patients with epithelial ovarian cancer. The expression of GOLPH3 protein in tumor tissue was evaluated using immunohistochemistry. Seventy-five patients with epithelial ovarian cancer with the data of GOLPH3 expression and follow-up were included. GOLPH3 overexpression was significantly associated with advanced stage, histology, high grade, and lymph node metastases (P < 0.05). Kaplan-Meier analysis showed that patients with GOLPH3 overexpression had significantly poorer overall survival than those with low expression of GOLPH3 (log-rank P < 0.001). In the multivariate Cox proportional hazards analysis, GOLPH3 overexpression was independently associated with poorer overall survival (hazard ratio [HR] = 3.60; 95 % confidence interval (CI0 1.14-11.33, P = 0.03). Therefore, overexpression of GOLPH3 protein is closely related to poorer prognosis in patients with epithelial ovarian cancer.

Aberrant promoter methylation and silencing of RASSF2A gene in cervical cancer.

AIM: Ras association domain family (RASSF)2A as a negative effector of Ras protein is inactivated by promoter hypermethylation in many cancers. This study evaluated the methylation status of RASSF2A in cervical cancer (CC) and its correlation with clinicopathological characteristics. METHODS: Methylation-specific polymerase chain reaction and reverse transcriptase polymerase chain reaction were utilized to analyze the methylation status and RASSF2A mRNA expression in four CC cell lines and tissue samples from 25 normal controls and 46 CC patients. The CC cell lines also were treated with the methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC). RESULTS: Expression of RASSF2A was downregulated in all cell lines and CC tissue samples. Hypermethylation of RASSF2A was detected in all cell lines and 26 of 46 (56.5%) CC samples. No methylation of RASSF2A was found in the normal cervical tissues. A decreased level (P < 0.05) of RASSF2A expression was observed among RASSF2A-methylated CC cases (0.1002 ± 0.0377, mean ± standard deviation) compared to unmethylated cases (0.2882 ± 0.0642, mean ± standard deviation). After treatment with 5-aza-dC, loss of RASSF2A expression was restored in four CC cell lines. RASSF2A methylation was significantly different in patients with or without lymph node metastasis (90% vs 47.2%, respectively; P < 0.05). CONCLUSION: Promoter hypermethylation of RASSF2A is observed in CC, while not in normal cervical tissues. RASSF2A is inactivated in CC by promoter hypermethylation and may play a role in cervical carcinogenesis.

[Expression of KATP in pulmonary artery smooth muscle cells under hypoxia-hypercapnia condition and the relationship with p38 MAPK pathway].

The aim of the present study is to investigate the expressions of ATP-sensitive K(+) channels (KATP) in pulmonary artery smooth muscle cells (PASMCs) and the relationship with p38 MAPK signal pathway in rats. Male SD rat PASMCs were cultured in vitro, and a model of hypoxia and hypercapnia was reconstructed. PASMCs were divided to normal (N), hypoxia-hypercapnia (H), hypoxia-hypercapnia+DMSO incubation (HD), hypoxia-hypercapnia+SB203580 (inhibitor of p38 MAPK pathway) incubation (HS) and hypoxia-hypercapnia+Anisomycin (agonist of p38 MAPK pathway) incubation (HA) groups. Western blot was used to detect the protein expression of SUR2B and Kir6.1; semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of SUR2B and Kir6.1. The results demonstrated that: (1) Compared with N, H, HD and HS groups, the expressions of Kir6.1 mRNA and protein in PASMCs of HA group were decreased significantly (P < 0.01), but there were no differences among N, H, HD and HS groups (P > 0.05); (2) Compared with N group, the expressions of SUR2B mRNA and protein in H, HD, HS and HA groups were increased significantly (P < 0.05), but there were no differences among H, HD, HS and HA groups (P > 0.05). The results imply that: (1) Hypoxia-hypercapnia, SB203580 didn't change the expressions of Kir6.1 mRNA and protein in PASMCs, but Anisomycin decreased the expressions of Kir6.1 mRNA and protein, so Kir6.1 may be regulated by the other subfamily of MAPK pathway; (2) Hypoxia-hypercapnia raised SUR2B mRNA and protein expressions in PASMCs, but SB203580 and Anisomycin did not affect the changes, so the increasing of SUR2B mRNA and protein induced by hypoxia-hypercapnia may be not depend on p38 MAPK pathway.

[Calcium-activated chloride channels are involved in two-phase hypoxic pulmonary vasoconstriction in rat pulmonary arteries].

The aim of the present study was to investigate the roles of calcium-activated chloride channels (Cl(Ca)) in the two-phase hypoxic pulmonary vasoconstriction (HPV). The second pulmonary artery branches were dissected from male Sprague-Dawley rats, and the changes in vascular tone were measured by using routine blood vascular perfusion in vitro. The result showed that, under normoxic conditions, Cl(Ca) inhibitors (NFA and IAA-94) significantly relaxed second pulmonary artery contracted by norepinephrine (P < 0.01), but merely had effects on KCl-induced second pulmonary artery contractions. A biphasic contraction response was induced in second pulmonary artery ring pre-contracted with norepinephrine exposed to hypoxic conditions for at least one hour, but no biphasic contraction was observed in pulmonary rings pre-contracted with KCl. NFA and IAA-94 significantly attenuated phase II sustained hypoxic contraction (P < 0.01), and also attenuated phase I vasodilation, but had little effect on phase I contraction. These results suggest that Cl(Ca) is an important component forming phase II contraction in secondary pulmonary artery, but not involved in phase I contraction.

An optimal genomic DNA extraction method for shoots of four Dendrocalamus species based on membership function analysis.

High-quality genomic DNA extraction is fundamental for the study of gene cloning and expression in plants. Therefore, this study evaluated several methods for extracting genomic DNA from shoots of four Dendrocalamus species to determine the optimal technique. Genomic DNA was extracted using three different methods: a commercial DNA extraction kit method, a modified cetyltrimethylammonium bromide method and a sodium dodecyl sulfate method. A membership function analysis was employed to compare these methods. The results demonstrated that the commercial DNA extraction kit method was the most effective and comprehensive approach for extracting genomic DNA from shoots of four Dendrocalamus species. Furthermore, this study provided valuable insights into optimizing techniques for extracting genomic DNA in other bamboo species.

Real-world data of China: Analysis of HPV vaccine coverage and post-vaccination adverse reaction monitoring in Western Chinese provinces from 2018 to 2021.

To investigate the HPV vaccine coverage and post-vaccination adverse reactions in Gansu Province, Western China, from 2018 to 2021. Data on suspected adverse reactions to HPV vaccines were collected from the Chinese Vaccine Adverse Event Following Immunization (AEFI). Estimate the incidence rates of Common Adverse Reaction and Rare Adverse Reaction. HPV vaccine coverage among females in different age groups was calculated using data from the Gansu Provincial Immunization Information Platform. The first-dose HPV vaccine coverage rate among females aged 9 to 45 was 2.02%, with the lowest rate of less than 1% observed in females aged 9 to 14. From 2018 to 2021, the incidence rates of Common Adverse Reaction and Rare Adverse Reaction reported in females after HPV vaccination were 11.82 and 0.39 per 100,000 doses, respectively. Common Adverse Reaction included fever (5.52 per 100,000 doses), local redness and swelling (3.33 per 100,000 doses), fatigue (3.15 per 100,000 doses), headache (2.76 per 100,000 doses), as well as local induration and nausea/vomiting (1.97 per 100,000 doses). Adverse reactions mainly occurred within 1 day after vaccination, followed by 1 to 3 days after vaccination. The HPV vaccine coverage rate among females aged 9 to 14 in Gansu Province is remarkably low, and there is an urgent need to enhance vaccine coverage. From 2018 to 2021, the incidence of Adverse reaction Following Immunization HPV vaccination fell within the expected range, indicating the vaccine's safety profile.

Quantitative assessment of the relationship between p21 Ser31Arg polymorphism and cervical cancer.

Though many studies were published to assess the relationship between p21 Ser31Arg polymorphism and cervical cancer, there was no definite conclusion on this association. To provide a quantitative assessment of the relationship between p21 Ser31Arg polymorphism and cervical cancer, we performed a meta-analysis of 10 eligible studies (1,539 cases and 2,161 controls). All those 10 studies were from Asians. The odds ratios (OR) with 95% confidence intervals (95%CIs) were used to assess the strength of the association, and the pooled ORs were calculated for the codominant model (ArgArg vs. SerSer), the dominant model (ArgArg/SerArg vs. SerSer), and the recessive model (ArgArg vs. SerSer/SerArg). Meta-analysis of those 10 studies showed that there was no association between p21 Ser31Arg polymorphism and cervical cancer risk in Asians under all three models (ArgArg vs. SerSer: OR = 1.04, 95%CI 0.66-1.65, P = 0.86, I(2) = 78%; ArgArg/SerArg vs. SerSer: OR = 0.93, 95%CI 0.66-1.30, P = 0.66, I(2) = 81%; ArgArg vs. SerSer/SerArg: OR = 1.20, 95%CI 0.84-1.73, P = 0.32, I(2) = 72%). Sensitivity analysis performed by omitting each study in turn showed that the pooled results were stable. In summary, there is no association between p21 Ser31Arg polymorphism and cervical cancer risk in Asians. Further studies are needed to assess the possible association between p21 Ser31Arg polymorphism and cervical cancer risk in Caucasians.

Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating glomerular filtration rate in the Chinese population.

BACKGROUND: Previous studies have indicated that the performance of glomerular filtration rate (GFR) estimation equations vary according to the races of the target population. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has not been validated in the Chinese population including patients with chronic kidney disease (CKD) and healthy controls. METHODS: A total of 977 adult persons (682 patients with CKD and 295 healthy volunteers) from nine renal institutes of university hospitals located in nine geographic regions of China were enrolled in the study. A diagnostic test study comparing the CKD-EPI two-level and four-level race equation, the Modification of Diet in Renal Disease (MDRD) Study equation and the modified MDRD equation for Chinese (the Chinese equation). The (99m)Tc- diethylenetriamine pentaacetic acid dual plasma clearance was used as a reference method for measuring GFR. RESULTS: The mean age of participants was 48.3 ± 16.0 years and 479 (49.0%) were male. The CKD-EPI two-level race equation and the Chinese equation performed better than the MDRD Study equation and CKD-EPI four-level race equation, with less bias (median difference between estimated GFR and reference GFR, 0.2 and 0.3 versus -2.4 and 3.0 mL/min/1.73 m(2)), improved precision (interquartile range of the difference, 20.5 and 20.8 versus 23.4 and 20.5 mL/min/1.73 m(2)) and greater accuracy (percentage of estimated GFR within 30% of reference GFR, 73.4 and 73.0% versus 69.8 and 70.1%). CONCLUSIONS: The CKD-EPI two-level race equation and the Chinese equation performed similarly in the Chinese population, and both performed better than the MDRD Study equation and the CKD-EPI four-level race equation.

Fermented Angelica sinensis activates Nrf2 signaling and modulates the gut microbiota composition and metabolism to attenuate D-gal induced liver aging.

Aging is an inevitable physiological process associated with an imbalance in the oxidative defense system. Angelica sinensis, a kind of traditional Chinese medicine (TCM), has anti-oxidant effects and has been considered as a potential supplement in anti-aging treatment. Nevertheless, it has the disadvantages of slow efficacy and long duration of treatment. Fermentation, as an efficient biotechnological approach, is beneficial for improving the nutritional capacity of the material. Fermented TCMs are considered to be more effective. In this study, fermented Angelica sinensis (FAS) and non-fermented Angelica sinensis (NFAS) were used to investigate changes in the chemical constituents. Furthermore, the improvement effect of FAS on D-galactose-induced aging in mice and the potential mechanisms were explored. The results revealed that FAS and NFAS had different constituents under the influence of fermentation, such as 3-phenyllactic acid, L-5-hydroxytryptophan, taxifolin and methyl gallate. These elevated constituents of FAS might help increase the ability of FAS to improve aging. The aging model was established by intraperitoneal injection of D-galactose (2.5 g kg-1 day-1) for 44 days, and FAS (3 g kg-1 day-1) was administered daily by oral gavage after 2 weeks of induction with D-galactose. FAS was observed to significantly ameliorate changes associated with liver aging, such as reduction of MDA, AGEs and 8-OHdG. The contents of pro-inflammatory cytokines containing TNF-α, IL-1ß and IL-6 were significantly suppressed in the FAS group. In addition, FAS activated Nrf2 signaling better than NFAS, improved the expression of Nrf2, HO-1, NQO1, GCLC, GCLM and GSS, and further increased the activities of SOD, CAT and other antioxidant enzymes in the liver. Simultaneously, it had a certain repair effect on the liver tissues of mice. The intestinal microbiota analysis showed that FAS could regulate the microbiota imbalance caused by aging, increase the ratio of Firmicutes/Bacteroidetes by 95% and improve the relative abundance of beneficial bacteria related to Nrf2 signaling, such as Lactobacillus. Besides, fecal metabolite analysis identified uric acid as an evidential metabolite, suggesting that FAS participates in purine metabolism to improve aging. Therefore, the regulation of intestinal microbiota and metabolism may be one of the important mechanisms of FAS in alleviating hepatic oxidative stress via the gut-liver axis. The results of this study could provide information for the future development of postbiotic products that may have beneficial effects on the prevention or treatment of aging.