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Antihypertensive agents are frequently prescribed in kidney transplant recipients (KTRs). However, the frequency and patterns of prescribing antihypertensive agents remain uncharacterized in KTRs in China. Therefore, this investigation was carried out.Retrospective prescription data dated 2011 to 2018 from KTRs in China were accessed using the Hospital Prescription Analysis Program database. Information about sex, birth date, and identification number of the patient; city, date, and department of the medical visit; major diagnoses; and the generic names, specifications, quantities, and usage of prescribed drugs were collected. Antihypertensive agents were grouped into 5 classes: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics. The frequency and patterns of prescribing these antihypertensive agents were analyzed.Prescriptions from 174,749 KTRs (67.2% male; mean age, 42.5 [9.4] years) were obtained, and 58.2% of the patients were prescribed antihypertensive agents. The percentage of patients who received antihypertensive treatment increased from 52.9% in 2011 to 61.6% in 2018 and varied by city. Cyclosporine was associated with higher prescription frequency of antihypertensive agents than was tacrolimus (71.7% vs 63.4%; P 0.0001). During the 8-year study period, CCBs were most frequently prescribed (39.0%), followed by ARBs (31.9%), BBs (14.3%), ACEIs (11.6%), and diuretics (3.2%). The mean (SD) number of antihypertensive drugs prescribed per KTR was 1.7 (0.8). Almost half of KTRs (51.2%) received just 1 antihypertensive drug. Co-administration of 2 or more antihypertensive drugs presented an obviously upward trend. The most commonly prescribed 2-drug combination was CCB + ARB (44.8%), followed by CCB + BB (20.1%) and CCB + ACEI (13.0%). In the patients who received 3 antihypertensive drugs, the 2 most frequently prescribed combinations were CCB + ARB + BB (37.5%) and CCB + ARB + ACEI (32.7%). Specific data varied by both year and city.The prescribing patterns of antihypertensive agents in KTRs varied by city even within same country. Hence, more high-quality research studies on the use of antihypertensive agents in KTRs are needed.

ObjectiveClear and specific reporting of a research paper is essential for its validity and applicability. Some studies have revealed that the reporting of studies based on the clinical prediction models was generally insufficient based on the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist. However, the reporting of studies on contrast-induced nephropathy (CIN) prediction models in the coronary angiography (CAG)/percutaneous coronary intervention (PCI) population has not been thoroughly assessed. Thus, the aim is to evaluate the reporting of the studies on CIN prediction models for the CAG/PCI population using the TRIPOD checklist.DesignA cross-sectional study.MethodsPubMed and Embase were systematically searched from inception to 30 September 2021. Only the studies on the development of CIN prediction models for the CAG/PCI population were included. The data were extracted into a standardised spreadsheet designed in accordance with the ‘TRIPOD Adherence Assessment Form’. The overall completeness of reporting of each model and each TRIPOD item were evaluated, and the reporting before and after the publication of the TRIPOD statement was compared. The linear relationship between model performance and TRIPOD adherence was also assessed.ResultsWe identified 36 studies that developed CIN prediction models for the CAG/PCI population. Median TRIPOD checklist adherence was 60% (34%–77%), and no significant improvement was found since the publication of the TRIPOD checklist (p=0.770). There was a significant difference in adherence to individual TRIPOD items, ranging from 0% to 100%. Moreover, most studies did not specify critical information within the Methods section. Only 5 studies (14%) explained how they arrived at the study size, and only 13 studies (36%) described how to handle missing data. In the Statistical analysis section, how the continuous predictors were modelled, the cut-points of categorical or categorised predictors, and the methods to choose the cut-points were only reported in 7 (19%), 6 (17%) and 1 (3%) of the studies, respectively. Nevertheless, no relationship was found between model performance and TRIPOD adherence in both the development and validation datasets (r=−0.260 and r=−0.069, respectively).ConclusionsThe reporting of CIN prediction models for the CAG/PCI population still needs to be improved based on the TRIPOD checklist. In order to promote further external validation and clinical application of the prediction models, more information should be provided in future studies.

To explore the clinical efficacy and safety of neoadjuvant chemotherapy (NACT) combined with minimally invasive laparoscopic cytoreductive surgery in the treatment of patients with advanced ovarian cancer (AOC).The clinical data of 116 patients with AOC were divided into NACT group (NACT combined with laparoscopic cytoreductive surgery, n=58) and control group (cytoreductive surgery alone, n=58). The short-term efficacy, surgery-related indexes, incidence of adverse reactions, and changes in levels of serum human epididymis protein 4 (HE4), vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) before and after treatment were compared between the two groups. The survival status of patients after treatment was recorded.The operation time, intraoperative blood loss, ascites volume, postoperative ventilation time, and average postoperative length of hospitalization in NACT group were all significantly shorter and less than those in the control group. The optimal cytoreduction rate in NACT group was far higher than that in the control group. The overall response rate in NACT group was obviously higher than that in the control group. After treatment, the levels of serum HE4, VEGF and CA125 greatly declined in the two groups compared with those before treatment, while they were obviously lower in the NACT group than those in the control group. The follow-up results revealed that the median overall survival (OS) was 31.1 months and 28.9 months, and the 3-year OS rate was 43.1% (25/58) and 31.0% (18/58), respectively, in the NACT group and control group.NACT can significantly shorten the duration of cytoreductive surgery of AOC, reduce intraoperative blood loss, accelerate postoperative recovery, raise the optimal cytoreduction rate, and enhance the clinical efficacy, without greatly improving the survival of patients.

High-dose-rate (HDR) brachytherapy (BT) is an essential treatment for cervical cancer, one of the most prevalent gynecological malignant tumors. In HDR BT, high radiation doses can be delivered to the tumor target with the minimum radiation doses to organs at risk. Despite the wide use of the small HDR 192Ir source, as the technique has improved, the HDR 60Co source, which has the same miniaturized geometry, has also been produced and put into clinical practice. Compared with 192Ir (74 days), 60Co has a longer half-life (5.3 years), which gives it a great economic advantage for developing nations. The aim of the study was to compare 60Co and 192Ir sources for HDR BT in terms of both dosimetry and clinical treatment. The results of reports published on the use of HDR BT for cervical cancer over the past few years as well as our own research show that this treatment is safe and it is feasible to use 60Co as an alternative source.

Ovarian cancer (OC) is the third commonest gynecological malignancy worldwide. The long non-coding (lnc)RNA microRNA (miR)155HG functions as an oncogene in different human cancers. However, the function and molecular mechanism of miR155HG in OC remain elusive. The present study indicated that the expression levels of miR155HG and tyrosinase-related protein 1 (TYRP1) were significantly increased, whereas that of miR155-5p was decreased in OC tissues and cells, as detected by real-time quantitative polymerase chain reaction. It was demonstrated that knockdown of miR155HG markedly inhibited OC cell viability, migration and invasion while promoting apoptosis, as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, Transwell and western blot assays. Mechanistically, it was revealed that miR155HG and TYRP1 were both targeted by miR-155-5p with complementary binding sites in the 3' untranslated region. A dual-luciferase reporter assay was used to confirm the targeting relationship between miR155HG, miR-155-5p and TYRP1. In addition, the interaction between miR155HG and miR-155-5p was further demonstrated by radioimmunoprecipitation and pull-down assays. In addition, feedback approaches determined that miR-155-5p inhibition or TYRP1 overexpression markedly reversed the inhibitory effects of miR155HG knockdown on OC cell viability, migration and invasion as well as weakened the promotive effect of miR155HG knockdown on OC cell apoptosis. Thus, miR155HG silencing inhibited the malignant biological behavior of OC cells by targeting the miR-155-5p/TYRP1 axis. The present study provides novel insights into the underlying mechanism of OC progression.

In present study, the apoptosis induction and proliferation suppression effects of l -phenylalanine ( l -Phe) on fibroblasts were confirmed. The action sites of l -Phe on fibroblasts suppression were deduced to be calcium sensitive receptor (CaSR) which could cause the release of endoplasmic reticulum (ER) Ca2+ stores; disruption of intracellular Ca2+ homeostasis triggers cell apoptosis via the ER or mitochondrial pathways. The down-regulation of CaSR were observed after the application of l -Phe, and the results those l -Phe triggered the increasing of intracellular Ca2+ concentration and calcineurin expression, and then the apoptosis and increasing G1 fraction of fibroblasts have verified our deduction. Hence, l -Phe could be seen as a kind of anti-fibrotic drugs for the crucial participation of fibroblast in the occurrence of fibrosis. And then, poly(p-dioxanone-co- l -phenylalanine) (PDPA) which could prolong the in-vivo anti-fibrotic effect of l -Phe for the sustained release of l -Phe during its degradation could be treated as anti-fibrotic polymer prodrugs. Based on the above, the in vivo anti-fibrotic function of PDPA was evaluated in rabbit ear scarring, rat peritoneum lipopolysaccharide, and rat sidewall defect/cecum abrasion models. PDPA reduced skin scarring and suppressed peritoneal fibrosis and post operation adhesion as well as secretion of transforming growth factor-β1 in injured tissue. These results indicate that PDPA is an effective agent for preventing fibrosis following tissue injury. Statement of Significance We have previously demonstrated that poly(p-dioxanone-co- l -phenylalanine) (PDPA) could induce apoptosis to fibroblast and deduced that the inhibitory effect comes from l -phenylalanine. In present study, the inhibition mechanism of l -phenylalanine on fibroblast proliferation was demonstrated. The calcium sensitive receptor (CaSR) was found to be the action site. The CaSR was downregulated after the application of l -phenylalanine, and then the ER Ca2+ stores were released. The released Ca2+ can simultaneously activate Ca2+/calcineurin and then trigger apoptosis and G1 arrest of fibroblast. Hence, l -phenylalanine could be seen as anti-fibrosis drug and PDPA which conjugate l -phenylalanine by hydrolytic covalent bonds could be seen as l -phenylalanine polymer prodrug. Based above, the in vivo anti-fibrotic function of PDPA were verified in three different animal models.

Ovarian cancer is considered to be the most fatal reproductive cancers. Melphalan is used to treat ovarian cancer as an intraperitoneal chemotherapy agent. However, elucidating its pharmacokinetic behavior and preparing it for administration are challenging since it undergoes spontaneous hydrolysis. In this study, melphalan is transformed into a macromolecular prodrug by copolymerizing with p-dioxanone. The hydrophobicity of copolymer chains protects melphalan from hydrolysis. Poly(p-dioxanone-co-melphalan; PDCM) is electrosprayed and converted into nanoparticles (PDCM NPs) with diameters of ~300–350 nm to facilitate its intracellular delivery. UPLC-MS and HPLC are applied to verify and monitor the release of melphalan from PDCM NPs. PDCM NPs could suppress the proliferation of SKOV-3 cells. The IC50 of 4.3% melphalan-containing PDCM-3 NP was 70 mg/L, 72 h post administration. These suppression characteristics not only affected by the degradation and then the extracellular release of melphalan from PDCM NPs, but also the uptake via phagocytosis phenomenon in SKOV-3 cells. As revealed by flow cytometry, phagocytosis is a first-order process. Once phagocytosed, PDCM NPs are digested by lysosomes, causing a rapid release of melphalan into the cytoplasm, which ultimately causes suppression of SKOV-3 cell proliferation. Finally, the in vivo antitumor effects of PDCM NPs are verified in xenograft ovarian carcinoma. After a 20-day treatment, the tumor growth rate of the PDCM-3 NP group was (266 ± 178%) which was lower than those in the free melphalan group (367 ± 150%) and control group (648 ± 149%). Besides, significant tissue necrosis and growth suppression were observed in animals administered injections of PDCM NPs. Furthermore, the in vivo tracing results of Nile red-labeled PDCM NPs demonstrated that PDCM-3 NPs might be phagocytosed by macrophages and then taken to adjacent lymph nodes, which is a way of prevention or early treatment of lymphatic metastasis of tumors.

Purpose Acid-suppressive medications are widely used in non–intensive care unit (non-ICU) patients for stress ulcer (SU) prophylaxis. However, SU prophylaxis in this population is still controversial. The purpose of this study was to systematically evaluate the efficacy and tolerability of these agents for SU prophylaxis in non-ICU patients. Methods Electronic databases including Cochrane, ClinicalTrials.gov , Ovid-Medline, Embase, Chinese CNKI, and Wanfang Data were systematically searched on July 10, 2019, for randomized controlled trials (RCTs) that evaluated acid-suppressive medications in non-ICU patients. Network meta-analysis and pairwise meta-analysis were performed to calculate odds ratios (ORs) and 95% CIs. A random-effects model was used for generating pooled estimates. The primary outcome was occurrence of SU bleeding, and the adverse drug events (ADEs) were described as the secondary outcome. Findings A total of 17 RCTs involving 1985 patients were eligible. Meta-analysis results indicated that the occurrence of SU bleeding was significantly decreased with all acid-suppressive medications compared with placebos (gastric mucosa protectants, OR = 0.29 [95% CI, 0.14–0.61]; H2-receptor antagonists, OR = 0.3 [95% CI, 0.18–0.50]; proton pump inhibitors [PPIs]: OR = 0.08 [95% CI, 0.04–0.16]). The occurrence of SU bleeding was significantly decreased with PPIs compared with gastric mucosa protectants (OR = 0.29; 95% CI, 0.12–0.72) and H2-receptor antagonists (OR = 0.28; 95% CI, 0.16–0.48). There was no significant difference between any 2 classes of PPIs on SU bleeding or any 2 acid-suppressive medications on ADEs. Implications PPIs could significantly decrease SU bleeding risk without increasing ADEs than other acid-suppressive medications for SU prophylaxis in non-ICU patients. However, RCTs of high quality were required to confirm the findings of this investigation.

Purpose This study explores factors that affect behavior in critically ill patients receiving continuous renal replacement therapy (CRRT) with imipenem and provides dosing regimens for these patients. Methods A prospective, open-label study was conducted in a clinical setting. Both blood and effluent samples were collected pairwise at the scheduled time points. Plasma and effluent imipenem concentrations were determined by HPLC-UV. A population pharmacokinetic model was developed using a nonlinear mixed-effects modeling method. The final model was evaluated by a bootstrap and visual predictive check. A population pharmacokinetic and pharmacodynamic analysis using Monte Carlo simulations was performed to explore the effects of empirically used dosing regimens (0.5 g q6h, 0.5 g q8h, 0.5 g q12h, 1 g q6h, 1 g q8h, and 1 g q12h) on the probability of target attainment. Findings Thirty patients were included in the population model analysis. Imipenem concentration data were best described by a 3-compartment model (central, peripheral, and dialysis compartments). The clearance of the dialysis compartment (CLd) was used to characterize drug elimination from the dialyzer. Creatinine clearance (CrCl) was the covariate that influenced the central clearance (CLc), and the effects of dialysate flow (Qd) was significant for CLd. Model validation revealed that the final model had qualified stability and acceptable predictive properties. A pharmacokinetic and pharmacodynamic analysis was conducted by Monte Carlo simulation, and patients were categorized into 12 subgroups based on different CrCl values ( 90 mL/min) and Qd values (300, 500, and 1000 mL/h). Under the same MIC value and administration regimen, probability of target attainment values decreased with an increase of CrCl and Qd. Implications CrCl and Qd had significant effects on CLc and CLd, respectively. The proposed final model may be used to guide practitioners in imipenem dosing in this specific patient population.

The axial chiral ligand 2,2′-bipyridyl-3,3′-dicarboxylic acid-1,1′-dioxide (H2bdd) has been employed to synthesize a 3D flexible microporous metal-organic framework (MOF), {[Cu2(bdd)2(bpa)2(H2O)2]·6.5H2O}n (1) (bpa = 1,2-bis(4-pyridyl)ethane), which contains an N-oxide open donor site. A gas adsorption test shows that complex 1′ (dehydrated 1) has a high adsorption selectivity for CO2 rather than N2 and H2. In particular, its CO2 adsorption isotherms exhibit an uncommon gate effect adsorption. The CO2 adsorption enthalpies were calculated from the adsorption isotherms. Compared to a flexible framework with respiration, 1′ displays a low energy consumption for sorbent regeneration, indicating the potential application of complex 1 in gas separation.

This study was aimed to explore the correlation between catechol-O-methyltransferase (COMT) gene polymorphisms and endometriosis susceptibility in Chinese Han population. This case-control study recruited 134 endometriosis patients and 139 healthy individuals. COMT gene rs4680, rs2020917, and rs4646312 polymorphisms in the subjects were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Association between COMT polymorphisms and endometriosis susceptibility was evaluated by χ2 test and adjusted by Logistic regression. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to present the relative risk of endometriosis. A allele of rs4680 was distinctly correlated with increased susceptibility of endometriosis (OR = 1.450, 95% CI = 1.012–2.076). However, when adjusted by the confounding factors, these associations become not significant. We failed to find any significant association between rs2020917 and endometriosis risk in the crude results. The adjusted results suggested that rs2020917 TT genotype and T allele were distinctly correlated with enhanced endometriosis risk (TT vs CC: P = .038, OR = 2.894, 95% CI = 1.060–7.903; T vs C: P = .039, OR = 1.481, 95% CI = 1.021–2.149). Besides, rs4646312 C allele was significantly correlated with endometriosis risk both in the crude (P = .027, OR = 1.502, 95% CI = 1.047–2.154) and adjusted (P = .019, OR = 1.564, 95% CI = 1.078–2.269) results. COMT polymorphisms might predict the occurrence of endometriosis.