TG/HDL-C ratio is positively associated with risk and severity of CHD among NAFLD patients: a case control study.

Objective: This study aimed to explore the association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and the risk and severity of CHD among NAFLD patients. Methods: This retrospective study included 278 patients with NAFLD and chest pain. The TG/HDL-C ratio was calculated and coronary angiography performed. All individuals were divided into NAFLD + CHD and NAFLD groups. The severity of coronary artery stenosis is quantified using the Gensini score based on angiographic results. In NAFLD patients, the association between the TG/HDL-C ratio and the risk and severity of CHD was explored. Results: CHD was detected in 139 of 278 patients. Compared to NAFLD group, multivariate logistic regression showed that TG/HDL-C ratio was a risk factor for CHD among NAFLD patients after adjustment for confounding factors with the odds ratio (OR 1.791, 95% CI 1.344-2.386, P<0.001). Further analysis using multivariate logistic regression based on tertiles revealed that, after adjusting for confounding factors, compared to the T1 group, the risk of CHD in the T2 group was 2.17-fold higher (OR, 2.17; 95% CI, 1.07-4.38; P = 0.031). Similarly, the risk of CHD in the T3 group increased by 2.84-fold (OR, 2.84; 95% CI, 1.36-5.94; P = 0.005). The multifactor linear regression analysis showed each 1-unit increase in TG/HDL-C ratio in the NAFLD + CHD group was associated with a 7.75-point increase in Gensini score (ß=7.75, 95% CI 5.35-10.15, P<0.001). Conclusion: The TG/HDL-C ratio was positively correlated with CHD risk and reflected coronary atherosclerosis severity in NAFLD patients.

Whole-Exome Sequencing Identifies Germline BLM Mutation in Ovarian Hepatoid Adenocarcinoma with Favorable Response to Niraparib and Anlotinib Combination Therapy-A Case Report and Literature Review.

Hepatoid adenocarcinoma of the ovary represents a rare and malignant extrahepatic tumor that shares morphological and immunophenotypic similarities with hepatocellular carcinoma. Due to the ambiguous histomorphology and aggressive behavior, the diagnosis and management of hepatoid adenocarcinoma of the ovary present unique challenges. Here, we present a 67-year-old woman with massive ascites and disseminated peritoneal implants at initial diagnosis. She was treated with six cycles of neoadjuvant therapy (albumin-bound paclitaxel + nedaplatin + bevacizumab) and a debulking surgery, followed by eight cycles of postoperative adjuvant therapy (albumin-bound paclitaxel + carboplatin + bevacizumab). Elaborate pathology workup found significant involvement of angiogenesis in the tumor and confirmed the diagnosis via immunohistochemistry. Further molecular characterization of the tumor by whole-exome sequencing (WES) revealed a novel heterozygous germline mutation (NM_000057.2, c.1290_1291delinsATCAGGCCTCCATAG, p.Y430fs1) in gene BLM, likely pathogenic, suggesting a potential candidate for Poly (ADP-ribose) polymerase (PARP) inhibitors. For the maintenance therapy, she received a combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib. As of now, the patient has achieved a partial response, with no apparent evidence of disease progression observed nearly 30 months. Our study sheds light on the WES-based profiling in rare cancers to screen for any treatable targets with otherwise no standard therapeutic options. The promising results with the niraparib-anlotinib combination suggest its potential as a maintenance therapy option for hepatoid adenocarcinoma of the ovary, which warrants validation in future larger cohort.

Zhibai dihuang pill (ZBDH) exhibits therapeutic effects on idiopathic central sexual precocity in rats by modulating the gut microflora.

To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.

Metagenomic sequencing reveals viral diversity of mosquitoes from Shandong Province, China.

Mosquitoes carry a large number of known and unknown viruses, some of which could cause serious diseases in humans or animals. Metagenomic sequencing for mosquito viromes is crucial for understanding the evolutionary history of viruses and preventing emerging mosquito-borne diseases. We collected 1,598 mosquitoes belonging to four species from five counties in Shandong Province, China in 2021. They were grouped by species and sampling locations and subjected to metagenomic next-generation sequencing for the analysis of the viromes. A total of 233,317,352 sequencing reads were classified into 30 viral families and an unclassified group. Comparative analysis showed that mosquitoes in Shandong Province generally possessed host-specific virome. We detected mosquito-borne viruses including Japanese encephalitis virus, Getah virus, and Kadipiro virus in Culex tritaeniorhynchus and Anopheles sinensis samples. Phylogenetic analysis showed that these pathogenic viruses may have existed in mosquitoes in Shandong Province for a long time. Meanwhile, we identified 22 novel viruses belonging to seven families and the genus Negevirus. Our study comprehensively described the viromes of several common mosquito species in Shandong Province, China, and demonstrated the major role of host species in shaping mosquito viromes. Furthermore, the metagenomic data provided valuable epidemiological information on multiple mosquito-borne viruses, highlighting the potential risk of infection transmission. IMPORTANCE: Mosquitoes are known as the source of various pathogens for humans and animals. Culex tritaeniorhynchus, Armigeres subalbatus, and Anopheles sinensis have been found to transmit the Getah virus, which has recently caused increasing infections in China. Cx. tritaeniorhynchus and Culex pipiens are the main vectors of Japanese encephalitis virus and have caused epidemics of Japanese encephalitis in China in past decades. These mosquitoes are widely present in Shandong Province, China, leading to a great threat to public health and the breeding industry. This study provided a comprehensive insight into the viromes of several common mosquito species in Shandong Province, China. The metagenomic sequencing data revealed the risks of multiple pathogenic mosquito-borne viruses, including Japanese encephalitis virus, Getah virus, and Kadipiro virus, which are of great importance for preventing emerging viral epidemics.

Association of previous stillbirth with subsequent perinatal outcomes: a systematic review and meta-analysis of cohort studies.

OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between stillbirth and various perinatal outcomes in subsequent pregnancy. DATA SOURCES: PubMed, the Cochrane Library, Embase, Web of Science, and CNKI databases were searched up to July 2023. STUDY ELIGIBILITY CRITERIA: Cohort studies that reported the association between stillbirth and perinatal outcomes in subsequent pregnancies were included. METHODS: We conducted this systematic review and meta-analysis in accordance with the PRISMA guidelines. Statistical analysis was performed using R and Stata software. We used random-effects models to pool each outcome of interest. We performed a meta-regression analysis to explore the potential heterogeneity. The certainty (quality) of evidence assessment was performed using the GRADE approach. RESULTS: Nineteen cohort studies were included, involving 4,855,153 participants. From these studies, we identified 28,322 individuals with previous stillbirths who met the eligibility criteria. After adjusting for confounders, evidence of low to moderate certainty indicated that compared with women with previous live births, women with previous stillbirths had higher risks of recurrent stillbirth (odds ratio, 2.68; 95% confidence interval, 2.01-3.56), preterm birth (odds ratio, 3.15; 95% confidence interval, 2.07-4.80), neonatal death (odds ratio, 4.24; 95% confidence interval, 2.65-6.79), small for gestational age/intrauterine growth restriction (odds ratio, 1.3; 95% confidence interval, 1.0-1.8), low birthweight (odds ratio, 3.32; 95% confidence interval, 1.46-7.52), placental abruption (odds ratio, 3.01; 95% confidence interval, 1.01-8.98), instrumental delivery (odds ratio, 2.29; 95% confidence interval, 1.68-3.11), labor induction (odds ratio, 4.09; 95% confidence interval, 1.88-8.88), cesarean delivery (odds ratio, 2.38; 95% confidence interval, 1.20-4.73), elective cesarean delivery (odds ratio, 2.42; 95% confidence interval, 1.82-3.23), and emergency cesarean delivery (odds ratio, 2.35; 95% confidence interval, 1.81-3.06) in subsequent pregnancies, but had a lower rate of spontaneous labor (odds ratio, 0.22; 95% confidence interval, 0.13-0.36). However, there was no association between previous stillbirth and preeclampsia (odds ratio, 1.72; 95% confidence interval, 0.63-4.70) in subsequent pregnancies. CONCLUSION: Our systematic review and meta-analysis provide a more comprehensive understanding of adverse pregnancy outcomes associated with previous stillbirth. These findings could be used to inform counseling for couples who are considering pregnancy after a previous stillbirth.

Environmental Surveillance of Human Astroviruses in Jinan City of China, 2020-2021.

Human astroviruses (HAstVs) are a significant etiological agent of acute gastroenteritis in children. In order to investigate the circulation of HAstVs during the COVID-19 pandemic, a 2-year environmental surveillance was conducted in Jinan between 2020 and 2021. A total of 24 sewage samples were collected and concentrated. Real-time PCR indicated a positive rate of 83.3%, 79.2% (19/24), and 62.5% for classic, MLB, and VA types of HAstV in sewage samples, respectively, with genomic copies ranging from 6.4 × 103 to 3.7 × 107, 3.2 × 104 to 2.2 × 106, and 1.2 × 104 to 1.6 × 107 l-1. Next-generation sequencing (NGS) analysis on complete ORF2 amplicons from each sewage concentrate revealed the presence of 11 HAstV types, including HAstV-1, -2, -4, -5, MLB1, and VA1 to VA6, as well as non-human animal astroviruses. The most abundant HAstV types were HAstV-1, -4, and -5, which accounted for 70.3%, 12.6%, and 9.1% of total HAstV reads, respectively. Phylogenetic analysis revealed that the sequences obtained in this study were segregated into multiple transmission lineages, yet exhibited less genetic divergence among themselves than with foreign strains. These findings provide insight into the genotype diversity and genetic characterization of HAstVs during the COVID-19 pandemic, and highlight the effectiveness of utilizing NGS approaches to investigate sewage HAstVs.

Effect of calcium ion concentration on the ORR performance of Pd/C catalysts.

Noble metal electrocatalysts prepared by microbial methods have attracted extensive attention because of their environmental protection and easy preparation. However, the preparation of electrocatalysts by microbial methods has problems such as large nanoparticles size and low loading rate. In this study, the porous gel co-embedded with Shewanella and alginate is prepared as the adsorption matrix to further enhance its mass transfer and adsorption efficiency. The effect of calcium ion concentration on catalyst performance is explored by optimizing the CaCl2 concentration to expose more adsorption sites. The results show that when the Ca2+ concentration is 0.025 mmol L-1, the prepared catalyst has the smallest size and the highest Pd loading, and exhibits the best electrochemical activity and stability. This provides a new idea for the preparation of electrocatalysts by microbial methods.

Atrial Fibrillation and Clinical Outcomes of Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-Analysis of Adjusted Effect Estimates.

BACKGROUND: The impact of atrial fibrillation (AF) on the clinical outcomes in patients with acute ischemic stroke (AIS) who received endovascular thrombectomy remains unclear. We aimed to perform a meta-analysis of adjusted effect estimates to examine the association between the presence of AF and the clinical outcomes in patients with AIS who received endovascular thrombectomy. METHODS AND RESULTS: We searched PubMed, Embase, and the Cochrane database between January 1, 2013 and July 10, 2023. Data were meta-analyzed to compare the outcomes among patients with AIS with and without AF who received endovascular thrombectomy. Our primary outcome was 90-day functional independence defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes included excellent independence (90-day modified Rankin Scale score of 0-1), 90-day mortality, symptomatic intracranial hemorrhage, and any intracranial hemorrhage. Eighteen observational studies comprising 16 096 patients with AIS (mean age, 70.1 years; women, 48.2%; 6862 with AF versus 9234 without AF) were included. There were no statistically significant differences for modified Rankin Scale score of 0 to 2 (pooled odds ratio [OR], 1.14 [95% CI, 0.95-1.37]; [95% prediction interval [PI], 0.72-1.80]), mortality (OR, 0.92 [95% CI, 0.79-1.08]; [95% PI, 0.77-1.11]), symptomatic intracranial hemorrhage (OR, 0.97 [95% CI, 0.71-1.32]; [95% PI, 0.43-2.17]), and any intracranial hemorrhage (OR, 1.08 [95% CI, 0.91-1.28]; [95% PI, 0.74-1.58]) among patients with AIS with and without AF. CONCLUSIONS: This meta-analysis detected no significant differences in 90-day functional outcomes, mortality, and intracerebral hemorrhage risk after endovascular thrombectomy in patients with AIS with and without AF. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD 42021293511.

Secure reversal of immune evasion from refractory NSCLC and highly contagious CoV-2 mutants by using 3D-engineered multifunctional biologics.

There is an imperative choice to develop a secure feasible strategy to address evasion dynamics of refractory tumors and SARS-CoV-2-variants, while stem cell-based protocol may be more reliable as its unique ability for resetting multifunctional immunity to address progressive tumor and the constantly-evolving virus. In this study, spheroid-embryonoid stem cells from mature somatic cells were engineered as multifunctional biologics (3D-E/BSC) and inoculated in senile rhesus to identify secure potential against immune-evasion from viral-variants. Meanwhile, a cohort of eligible patients with stage IV NSCLC were approved for phase I clinical trials. Subsequently, long-lasting security and efficacy were validated by primate and clinical trials (p < 0.01) in that it could not only stimulate serological immunity, but also reset core immunity for hosts to address variant evasion after 3D-E/BSC withdrawal. Particularly, illustrated by single-cell evolving trajectory, 3D-E/BSC had securely reset senile thymus of aging hosts to remodel core immunity by rearranging naive rhythm to evolve TRGC2+/JCHAIN+NKT clusters to abolish tumoral and viral evasion dynamics with path-feedbacks of NSCLC and COVID-19 simultaneously activated, leading to continuous blockade of breakthrough infection of viral-mutants and long-term survival in one-third of terminal patients without adjuvant required. Our study may pioneer a practical multifunctional strategy to eliminate evasion of SARS-CoV-2 variants and refractory NSCLC so as for victims to restart a new life-equation.

Chemotherapy effect on myocardial fibrosis markers in patients with gynecologic cancer and low cardiovascular risk.

Background: Patients with gynecologic cancers experience side effects of chemotherapy cardiotoxicity. We aimed to quantify cardiac magnetic resonance (CMR) markers of myocardial fibrosis in patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy. Methods: This study is part of a registered clinical research. CMR T1 mapping was performed in patients with gynecologic cancer and low cardiovascular risk undergoing chemotherapy. The results were compared with those of age-matched healthy control subjects. Results: 68 patients (median age = 50 years) and 30 control subjects were included. The median number of chemotherapy cycles of patients was 9.0 (interquartile range [IQR] 3.3-17.0). Extracellular volume fraction (ECV) (27.2% ± 2.7% vs. 24.5% ± 1.7%, P < 0.001) and global longitudinal strain (-16.2% ± 2.8% vs. -17.4% ± 2.0%, P = 0.040) were higher in patients compared with controls. Patients with higher chemotherapy cycles (>6 cycles) (n=41) had significantly lower intracellular mass indexed (ICMi) compared with both patients with lower chemotherapy cycles (≤6 cycles) (n=27) (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 34.30 g/m2 [IQR 29.93-39.79 g/m2]; P = 0.002) and the control group (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 32.79 g/m2 [IQR 27.74-35.76 g/m2]; P = 0.002). Patients with two or more chemotherapy regimens had significantly lower ICMi compared with both patients with one chemotherapy regimen (27.45 ± 5.16 g/m2 vs. 33.32 ± 6.42 g/m2; P < 0.001) and the control group (27.45 ± 5.16 g/m2 vs. 33.02 ± 5.52 g/m2; P < 0.001). The number of chemotherapy cycles was associated with an increase in the ECV (Standard regression coefficient [ß] = 0.383, P = 0.014) and a decrease in the ICMi (ß = -0.349, P = 0.009). Conclusion: Patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy have diffuse extracellular volume expansion, which is obvious with the increase of chemotherapy cycles. Myocyte loss may be part of the mechanism in patients with a higher chemotherapy load. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR-DDD-17013450.

Recurrent choriocarcinoma complicated with leprosy during chemotherapy: A case report and literature review.

RATIONALE: The global prevalence of leprosy has decreased substantially, and cases of leprosy infection are extremely rare in China. In this report, we present a case of recurrent choriocarcinoma complicated by leprosy infection during chemotherapy. PATIENT CONCERNS: A 24-year-old Chinese woman (gravida 3, para 2) presented to a local hospital with vaginal bleeding. Her medical history included a previous diagnosis of hydatidiform mole. DIAGNOSES, INTERVENTIONS AND OUTCOMES: The patient was diagnosed with choriocarcinoma and received chemotherapy in 6 cycles. Shortly after the initial treatment was completed, the disease recurred twice with resistance to multiple chemotherapeutic agents. In her second recurrence of choriocarcinoma, she was diagnosed with leprosy with many cutaneous nodules throughout her entire body. The patient was administered chemical treatment for leprosy with the multidrug therapy regimen after being diagnosed. To prevent exacerbating the infection, no immunotherapy was utilized to treat cancer, and the infection was well-controlled at the conclusion of anticancer therapy. LESSONS: Because of immunological reduction, cancer patients are susceptible to a variety of infections. For patients with cancer, prevention and early detection of rare infectious diseases should receive special attention. Immunotherapy must be used with caution when treating patients with cancer and infections.

Genomic characterization of an Omono River virus isolated from Culex tritaeniorhynchus in eastern China.

Omono River virus (OMRV) is a newly reported, unclassified RNA virus in the family Totiviridae, which infects mosquitoes and bats. In this study, we report the isolation of an OMRV strain SD76 from Culex tritaeniorhynchus captured in Jinan city, China. The cytopathic effect was characterized by cell fusion on C6/36 cell line. Its complete genome was 7611 nucleotides in length, with 71.4-90.4% similarities with other OMRV strains. Phylogenetic analysis based on complete genomes showed all OMRV-like strains can be divided into 3 groups with between-group distances ranging from 0.254 to 0.293. These results revealed that the OMRV isolate had high genetic diversity with those identified previously, and enriched the genetic information of family Totiviridae.

Massive fetomaternal hemorrhage in a monochorionic-diamniotic twin pregnancy: a case report.

Fetomaternal hemorrhage (FMH) result into severe, life-threatening fetal anemia and cause intrauterine death of the fetus. It is tough for an early diagnosis of FMH before pregnancy and few authors reported FMH in a twin pregnancy. Therefore, we reported a case of massive FMH. The patient felt a decrease in fetal movements at 33+5 gestational weeks. Cardiotocography showed sinusoidal heart rate patterns in one fetus. The fetal hemoglobin level in maternal blood was 6.4% (normal range for single pregnancy, 0.0%-2.0%). Since the patient was diagnosed with fetal distress, cesarean section was performed and both babies delivered to receive neonatal treatment. Severe anemia was apparent in both neonates, based on red blood cell count, hemoglobin concentration, and hematocrit of 0.75 × 1012/L and 0.61 × 1012/L, 2.8 g/dL and 2.4 g/dL, and 10.0% and 8.4%, respectively. The neonates were admitted to the intensive care unit for prematurity care and presently are well. In our experience, an early diagnosis of FMH contributed to saving fetus. Obstetricians should highlight fetal movements counting to every patient. Once massive FMH occurs in monochorionic twins, both fetuses may develop severe anemia and require emergency intervention.

Detection and diversity of human enteroviruses from domestic sewage in Weishan Lake region, eastern China, 2018-2019.

AIMS: Next generation sequencing (NGS) technology has been widely used in monitoring and identifying microbiomes in sewage. We aimed to evaluate the ability of NGS analysis in directly detecting enterovirus (EV) in sewage and to understand the diversity of EVs circulated in the residents in Weishan Lake region. METHODS AND RESULTS: Fourteen sewage samples were collected in Jining, Shandong Province, China from 2018 to 2019 and were parallelly investigated by the P1 amplicon-based NGS method and cell culture method. The results showed that 20 different serotypes belonging to species Enterovirus A (EV-A) (n = 5), EV-B (n = 13), and EV-C (n = 2) were identified by NGS in the sewage concentrates, which exceeded the number of types detected by cell culture method (n = 9). Echovirus 11 (E11), Coxsackievirus (CV) B5 and CVA9 were the most detected types in those sewage concentrates. Phylogenetic analysis revealed that E11 sequences obtained in this study belonged to genogroup D5 and had close genetic relationship with clinical sequences. CONCLUSIONS: Various EV serotypes circulated in populations near Weishan Lake. The combination of NGS technology into environmental surveillance will greatly contribute to improving our knowledge about EV circulation patterns in the population.

A comparison of low- versus standard-dose bridging alteplase in acute ischemic stroke mechanical thrombectomy using indirect methods.

Background: Whether low-dose alteplase is similar to standard-dose bridging alteplase prior to endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS) remains uncertain. Aims: The aim of this study was to compare the efficacy and safety outcomes of low- versus standard-dose bridging alteplase therapy (BT) in patients with acute ischemic stroke (AIS) who are eligible for intravenous thrombolysis (IVT) within 4.5 h after onset. Methods: We conducted an indirect comparison of low- versus standard-dose bridging alteplase before mechanical thrombectomy in AIS of current available clinical randomized controlled trials (RCTs) that compared direct mechanical thrombectomy treatment (dMT) to BT. Primary efficacy outcomes were functional independence and excellent recovery defined as a dichotomized modified Rankin Scale (mRS) 0-2 and 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage (ICH). Results: We included six RCTs of 2334 AIS patients in this analysis, including one trial using low-dose bridging alteplase (n = 103) and five trials using standard-dose bridging alteplase (n = 1067) against a common comparator (dMT). Indirect comparisons of low- to standard-dose bridging alteplase yielded an odds ratio (OR) of 0.84 (95% CI 0.47-1.50) for 90-day mRS 0-2, 1.18 (95% CI 0.65-2.12) for 90-day mRS 0-1, 1.21 (95% CI 0.44-3.36) for mortality, and 1.11 (95% CI 0.39-3.14) for successful recanalization. There were no significant differences in the odds for sICH (OR 1.05, 95% CI 0.32-3.41) or any ICH (OR 1.71, 95% CI 0.94-3.10) between low- and standard-dose bridging alteplase. Conclusion: Indirect evidence shows that the effects of low- and standard-dose bridging alteplase are similar for key efficacy and safety outcomes. Due to the wide confidence intervals, larger randomized trials comparing low- and standard-dose alteplase bridging therapy are required.

Near-real-time global gridded daily CO2 emissions 2021.

We present a near-real-time global gridded daily CO2 emissions dataset (GRACED) throughout 2021. GRACED provides gridded CO2 emissions at a 0.1° × 0.1° spatial resolution and 1-day temporal resolution from cement production and fossil fuel combustion over seven sectors, including industry, power, residential consumption, ground transportation, international aviation, domestic aviation, and international shipping. GRACED is prepared from the near-real-time daily national CO2 emissions estimates (Carbon Monitor), multi-source spatial activity data emissions and satellite NO2 data for time variations of those spatial activity data. GRACED provides the most timely overview of emissions distribution changes, which enables more accurate and timely identification of when and where fossil CO2 emissions have rebounded and decreased. Uncertainty analysis of GRACED gives a grid-level two-sigma uncertainty of value of ±19.9% in 2021, indicating the reliability of GRACED was not sacrificed for the sake of higher spatiotemporal resolution that GRACED provides. Continuing to update GRACED in a timely manner could help policymakers monitor energy and climate policies' effectiveness and make adjustments quickly.

Population Pharmacokinetic Analysis for Model-Based Therapeutic Drug Monitoring of Tacrolimus in Chinese Han Heart Transplant Patients.

BACKGROUND AND OBJECTIVE: Tacrolimus has become the first-line immunosuppressant for preventing rejection after heart transplantation. The present study aimed to investigate genetic variants and clinical factors affecting the variability of tacrolimus in Chinese Han heart transplant patients using a population pharmacokinetic approach. METHODS: The retrospective study included 53 hospitalized patients with 547 tacrolimus concentrations for analysis. Nonlinear mixed-effects modeling was used to develop the population pharmacokinetics model for tacrolimus in patients with heart transplants, followed by Monte Carlo simulations to design initial dosing regimens. RESULTS: In our study, the mutation rate of CYP3A4*18B (C>T) was 27.36%. An oral one-compartment model with first-order absorption and elimination was used to describe the pharmacokinetics of tacrolimus in heart transplant patients. In the final model, the estimated apparent clearance (CL/F) and volume of distribution (V/F) were 532.5 L/h [12.20% interindividual variability, IIV] and 16.87 L (23.16% IIV), respectively. Albumin, postoperative time, and rs2242480 (CYP3A4*18B) gene polymorphisms were the significant covariates affecting CL/F, and creatinine clearance had significant effects on the V/F. CONCLUSION: The population pharmacokinetic model of tacrolimus in heart transplant patients can better estimate the population and individual pharmacokinetic parameters of patients and can provide a reference for the design of individualized dosing regimens.

A real-world study of PARP inhibitors in 75 patients with platinum-sensitive recurrent ovarian cancer from China.

Objective: The aim of this study is to assess the efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) as a maintenance therapy for patients with platinum-sensitive recurrent epithelial ovarian cancer (PSROC) at the largest center of gynecologic oncology in Western China. Patients and methods: The efficacy of PARPi was evaluated by progression-free survival (PFS) and overall survival (OS) in this real-world single-center retrospective cohort study conducted at West China Second University Hospital. The safety of PARPi was assessed using Common Terminology Criteria for Adverse Events Version 5.0. Results: In this study, we included a total of 75 eligible patients, of which 54 (72.0%) received olaparib and 21 (28.0%) received niraparib. Among these patients, 24 (32.0%) had breast cancer susceptibility gene (BRCA) mutations, 27 (36.0%) achieved complete response after their last platinum-based therapy, and 22 (29.3%) had previously received ≥3rd-line chemotherapy. The median progression-free survival (mPFS) was 19.1 months (95% CI 8.5-29.7), and the median overall survival (mOS) had not been reached. Log-rank analysis revealed that age (<65 years old V.S. ≥65 years old) and previous lines of chemotherapy (2nd-line V.S. 3rd-line V.S. ≥4th-line) were associated with prolonged PFS (P <0.05). However, multivariate COX regression analysis did not identify any independent factors associated with prognosis (P >0.05). The most common grade≥3 adverse events in the olaparib group were anemia, thrombocytopenia, and leukopenia, while in the niraparib group, they were anemia and thrombocytopenia. Conclusion: This study confirmed that olaparib and niraparib are effective and tolerate for PSROC in real-world settings. At the follow-up endpoint, no independent prognostic factor associated with prolonged PFS was identified.

Myocardial edema during chemotherapy for gynecologic malignancies: A cardiac magnetic resonance T2 mapping study.

Objective: Myocardial edema is an early manifestation of chemotherapy-related myocardial injury. In this study, we used cardiac magnetic resonance (CMR) T2 mapping to assess myocardial edema and its changes during chemotherapy for gynecologic malignancies. Methods: We enrolled 73 patients receiving chemotherapy for gynecologic malignancies, whose the latest cycle was within one month before the beginning of this study, and 41 healthy volunteers. All participants underwent CMR imaging. Of the 73 patients, 35 completed CMR follow-up after a median interval of 6 (3.3 to 9.6) months. The CMR sequences included cardiac cine, T2 mapping, and late gadolinium enhancement. Results: Myocardial T2 was elevated in patients who were treated with chemotherapy compared with healthy volunteers [41ms (40ms to 43ms) vs. 41ms (39ms to 41ms), P = 0.030]. During follow-up, myocardial T2 rose further [40ms (39ms to 42ms) vs. 42.70 ± 2.92ms, P < 0.001]. Multivariate analysis showed that the number of chemotherapy cycles was associated with myocardial T2 elevation (ß = 0.204, P = 0.029). After adjustment for other confounders, myocardial T2 elevation was independently associated with a decrease in left ventricular mass (ß = -0.186; P = 0.024). Conclusion: In patients with gynecologic malignancies, myocardial edema developed with chemotherapy cycles increase, and was associated with left ventricular mass decrease. T2 mapping allows the assessment of myocardial edema and monitoring of its change during chemotherapy.