Two chromosome-level genome assemblies of Rhodiola shed new light on genome evolution in rapid radiation and evolution of the biosynthetic pathway of salidroside.

Rhodiola L. is a genus that has undergone rapid radiation in the mid-Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an important adaptogen in traditional medicines for centuries. However, a lack of high-quality chromosome-level genomes hinders in-depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome-level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat-retrotransposons (LTR-RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high-altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF-VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.

Real-world evidence of avatrombopag for the treatment of immune thrombocytopenia intolerant or ineffective to eltrombopag/hetrombopag.

Due to the limited real-world research on the application of avatrombopag (AVA) for immune thrombocytopenia (ITP) in China, we evaluated the effectiveness and safety of AVA in clinical practice. We included 121 adult ITP patients treated with AVA across three medical centres. Based on the reasons for choosing AVA, these patients were divided into eltrombopag (ELT)/hetrombopag (HET) intolerance group (IG), and ELT/HET unresponsive group (UG). Compared with UG, more patients in IG had a history of liver disease and received fewer treatments before AVA. Amongst all patients, 83% had platelet response (≥30 × 109/L) after AVA and 62% achieved complete response (≥100 × 109/L, CR). Sixty-two percent in IG and 56% in UG were able to discontinue more than one concomitant ITP medication. A total of 17 patients underwent multiple switches of thrombopoietin receptor agonists (TPO-RAs), resulting in an 88% platelet response rate. Sixty-three patients discontinued AVA, 27% were due to unaffordability. AVA was well tolerated in most patients. In the ITP population, AVA proved effective and safe, particularly in patients intolerant or unresponsive to ELT/HET. Patients benefited from TPO-RAs switches, particularly those undergoing multiple switches. However, many patients struggled with the long-term financial burden of AVA.

Association between Whole Grain Intake and Chronic Kidney Disease.

BACKGROUND: The relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. OBJECTIVE: This study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. METHODS: The present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. RESULTS: A total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. CONCLUSIONS: Increased whole grain intake was associated with a decreased risk of CKD in Chinese adults.

Associations between whole grains intake and new-onset hypertension: a prospective cohort study.

IMPORTANCE: Epidemiological evidences regarding the association between whole grain intake and the risk of new-onset hypertension are still controversial. OBJECTIVE: We aimed to investigate the relationship between whole grain intake and new-onset hypertension and examine possible effect modifiers in the general population. METHODS: A total of 10,973 participants without hypertension from the China Health and Nutrition Survey were enrolled, with follow-up beginning in 1997 and ending in 2015. Whole grain intake was assessed by 3 consecutive 24-h dietary recalls combined with a household food inventory. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression model after adjusting for potential risk factors. RESULTS: During a median follow-up of 7.0 years, 3,733 participants developed new-onset hypertension. The adjusted HRs (95% CIs) were as follows: for quartile 2 (HR: 0.52; 95% CI: 0.47-0.57), quartile 3 (HR: 0.46; 95% CI: 0.42-0.51), and quartile 4 (HR: 0.35; 95% CI: 0.31-0.38), compared with quartile 1. Different types of whole grain types, including wheat (adjusted HR, 0.35; 95% CI, 0.32-0.39), maize (adjusted HR, 0.50; 95% CI, 0.42-0.59), and millet (adjusted HR, 0.38; 95% CI, 0.30-0.48), showed significant associations with a reduced risk of hypertension. The association between whole grain intake and new-onset hypertension was stronger in individuals with older age (P for interaction < 0.001) and higher BMI (P for interaction < 0.001). CONCLUSION: Higher consumption of whole grains was significantly associated with a lower risk of new-onset hypertension. This study provides further evidence supporting the importance of increasing whole grain intake for hypertension prevention among Chinese adults.

Design, synthesis and triglyceride-lowering activity of tricyclic matrine derivatives for the intervention of non-alcoholic fatty liver disease.

Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Primary mechanism study revealed that upregulation of peroxisome proliferator-activated receptors α (PPARα)-carnitine palmitoyltransferase 1A (CPT1A) pathway mediated the efficacy of 7n. Our study provides powerful information for developing this kind of compound into a new class of anti-NAFLD candidates, and compound 7n is worthy of further investigation as an ideal lead compound.

Early Acute Kidney Injury Recovery in Elderly Patients Undergoing Valve Replacement Surgery.

OBJECTIVES: This study was designed to determine the incidence, contributing factors, and prognostic implications of acute kidney injury (AKI) recovery patterns in patients who experienced AKI after valve replacement surgery (VRS). DESIGN: A retrospective cohort study was conducted. SETTING: The work took place in a postoperative care center in a single large-volume cardiovascular center. PARTICIPANTS: Patients undergoing VRS between January 2010 and December 2019 were enrolled. INTERVENTION: Patients were categorized into three groups based on their postoperative AKI status: non-AKI, AKI with early recovery (less than 48 hours), and persistent AKI. MEASUREMENT AND MAIN RESULTS: The primary outcome was in-hospital major adverse clinical events. The secondary outcomes included in-hospital and 1-year mortality. A total of 4,161 patients who developed AKI following VRS were included. Of these, 1,513 (36.4%) did not develop postoperative AKI, 1,875 (45.1%) experienced AKI with early recovery, and 773 (18.6%) had persistent AKI. Advanced age, diabetes, New York Heart Association III-IV heart failure, moderate-to-severe renal dysfunction, anemia, and AKI stages 2 and 3 were identified as independent risk factors for persistent AKI. In-hospital major adverse clinical events occurred in 59 (3.9%) patients without AKI, 88 (4.7%) with early AKI recovery, and 159 (20.6%) with persistent AKI (p < 0.001). Persistent AKI was independently associated with an increased risk of in-hospital adverse events and 1-year mortality. In contrast, AKI with early recovery did not pose additional risk compared with non-AKI patients. CONCLUSIONS: In patients who develop AKI following VRS, early AKI recovery does not pose additional risk compared with non-AKI. However, AKI lasting more than 48 hours is associated with an increased risk of in-hospital and long-term adverse outcomes.

Construction and evaluation of a cloud follow-up platform for gynecological patients receiving chemotherapy.

BACKGROUND: Patient follow-up is an essential component of hospital management. In the current information era, the patient follow-up scheme is expected to be replaced by Internet technology. This study constructed a cloud follow-up platform for gynecological chemotherapy patients and assessed its cost-effectiveness and patients' feedback. METHODS: A total of 2,538 patients were followed up using a cloud follow-up system between January and October 2021. Prior to this, 690 patients were followed manually via telephone calls. Patients' characteristics, follow-up rate, satisfaction, and session duration were compared between the cloud follow-up and manual follow-up groups. In addition, the read rate of health education materials in the cloud follow-up group was analyzed. RESULTS: General information, including age, education attainment, cancer stage, and disease category, and follow-up rate (cloud: 6,957/7,614, 91.4%; manual: 1,869/2,070, 90.3%; P = 0.13) did not significantly differ between the two groups. The follow-up satisfaction of the cloud follow-up patients was significantly better than that of the manual follow-up group (cloud: 7,192/7,614, 94.5%; manual: 1,532/2,070, 74.0%; P<0.001). The time spent on the follow-up was approximately 1.2 h for 100 patients in the cloud follow-up group and 10.5 h in the manual follow-up group. Multivariate analysis indicated that the cloud follow-up group had significantly greater follow-up satisfaction (odds ratio: 2.239, 95% CI: 1.237 ~ 5.219). Additionally, the average follow-up duration of the cloud follow-up group decreased by 9.287 h (coefficient: -9.287, 95% CI: -1.439~-0.165). The read rate of health education materials was 72.9% in the cloud follow-up group. CONCLUSIONS: The follow-up effect of the cloud follow-up group was not inferior to that of the manual follow-up group. The cloud follow-up was more effective for prevention and control requirements in the post-epidemic era. Cloud follow-up can save medical resources, improve cost-effectiveness, provide sufficient health education resources for patients, and improve their satisfaction.

Long-term exposure to air pollutants and new-onset migraine: A large prospective cohort study.

BACKGROUNDS: Short-term exposure to air pollutants increases the risk of migraine, but the long-term impacts of exposure to multiple pollutants on migraine have not been established. The aim of this large prospective cohort study was to explore these links. METHODS: A total of 458,664 participants who were free of migraine at baseline from the UK Biobank were studied. Cox proportional hazards models were used to estimate the risk of new-onset migraine from combined long-term exposure to four pollutants, quantified as an air pollution score using principal component analysis. RESULTS: During a median (IQR) follow-up of 12.5 (11.8, 13.2) years, a total of 5417 new-onset migraine cases were documented. Long-term exposure to multiple air pollutants was associated with an increased risk of new-onset migraine, as indicated by an increased in the SDs of PM2.5 (hazard ratio (HR): 1.04, 95% CI: 1.01-1.06, P = 0.009), PM10 (HR: 1.07, 95% CI: 1.04-1.10, P < 0.001), NO2 (HR: 1.10, 95% CI: 1.07-1.13, P < 0.001) and NOx (HR: 1.04, 95% CI: 1.01-1.07, P = 0.005) in the main model. The air pollution score showed a doseresponse association with an increased risk of new-onset migraine. Similarly, compared with those of the lowest tertile, the HRs (95% CI) of new-onset migraine were 1.11 (95% CI: 1.04-1.19, P = 0.002) and 1.17 (95% CI: 1.09-1.26, P < 0.001) in tertiles 2 and 3, respectively, according to the main model (P trend < 0.001). CONCLUSION: Long-term individual and joint exposure to multiple air pollutants is associated with an increased risk of new-onset migraine.

Long-term air pollutants exposure and respiratory mortality: A large prospective cohort study.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Comparative transcriptome and metabolome analyses identified the mode of sucrose degradation as a metabolic marker for early vegetative propagation in bulbs of Lycoris.

Vegetative propagation (VP) is an important practice for production in many horticultural plants. Sugar supply constitutes the basis of VP in bulb flowers, but the underlying molecular basis remains elusive. By performing a combined sequencing technologies coupled with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry approach for metabolic analyses, we compared two Lycoris species with contrasting regeneration rates: high-regeneration Lycoris sprengeri and low-regeneration Lycoris aurea. A comprehensive multi-omics analyses identified both expected processes involving carbohydrate metabolism and transcription factor networks, as well as the metabolic characteristics for each developmental stage. A higher abundance of the differentially expressed genes including those encoding ethylene responsive factors was detected at bulblet initiation stage compared to the late stage of bulblet development. High hexose-to-sucrose ratio correlated to bulblet formation across all the species examined, indicating its role in the VP process in Lycoris bulb. Importantly, a clear difference between cell wall invertase (CWIN)-catalyzed sucrose unloading in high-regeneration species and the sucrose synthase-catalyzed pathway in low-regeneration species was observed at the bulblet initiation stage, which was supported by findings from carboxyfluorescein tracing and quantitative real-time PCR analyses. Collectively, the findings indicate a sugar-mediated model of the regulation of VP in which high CWIN expression or activity may promote bulblet initiation via enhancing apoplasmic unloading of sucrose or sugar signals, whereas the subsequent high ratio of hexose-to-sucrose likely supports cell division characterized in the next phase of bulblet formation.

Effects of apocynin on ISO-induced delayed afterdepolarizations in rat atrial myocytes and the underlying mechanisms.

We aimed to investigate the effect of apocynin (APO) on delayed afterdepolarizations (DADs) in rat atrial myocytes and the underlying mechanisms. Rat atrial myocytes were isolated by a Langendorff perfusion apparatus. DADs were induced by isoproterenol (ISO). Action potentials (APs) and ion currents were recorded by the whole-cell clamp technique. The fluorescent indicator fluo-4 was used to visualize intracellular Ca2+ transients, and western blotting was used to measure the expression of related proteins. The incidence of DADs in rat atrial myocytes increased significantly after ISO treatment, leading to an increased incidence of triggered activity (TA). The incidence of ISO-induced DADs and TA were reduced by 100.0 µM APO from 48.89% to 25.56% and 17.78% to 5.56%, respectively. In the range of 3.0 µM-300.0 µM, the effect of APO was concentration dependent, with a half maximal inhibitory concentration (IC50) of 120.1 µM and a Hill coefficient of 1.063. APO reversed the increase in transient inward current (Iti) and Na+/Ca2+-exchange current (INCX) densities induced by ISO in atrial myocytes. The frequency of spontaneous Ca2+ transients in atrial myocytes was reduced by 100.0 µM APO. Compared with ISO, APO downregulated the expression of NOX2 and increased the phosphorylation of PLNSer16 and the sarcoplasmic reticulum Ca2+-ATPase-2a (SERCA2a) level; however, it had little effect on ryanodine-receptor channel type-2 (RyR2). These findings showed that APO may block Iti and INCX and reduce intracellular Ca2+ levels in rat atrial myocytes, thus reducing the incidence of ISO-induced DADs and TA.

Genomic data provide a robust phylogeny backbone for Rhodiola L. (Crassulaceae) and reveal extensive reticulate evolution during its rapid radiation.

The Tibetan Plateau and adjacent mountain regions (TP; including the Tibetan Plateau, Himalaya, Hengduan Mountains and Mountains of Central Asia) harbor great biodiversity, some lineages on which may have undergone rapid radiations. However, only a few studies have investigated the evolutionary pattern of such diversification in depth using genomic data. In this study, we reconstructed a robust phylogeny backbone of Rhodiola, a lineage that may have undergone rapid radiation in the TP, using Genotyping-by-sequencing data, and conducted a series of gene flow and diversification analyses. The concatenation and coalescent-based methods yield similar tree topologies, and five well-supported clades were revealed. Potential gene flow and introgression events were detected, both between species from different major clades and closely related species, suggesting pervasive hybridization and introgression. An initial rapid and later slowdown of the diversification rate was revealed, indicating niche filling. Molecular dating and correlation analyses showed that the uplift of TP and global cooling in the mid-Miocene might have played an important role in promoting the rapid radiation of Rhodiola. Our work demonstrates that gene flow and introgression might be an important contributor to rapid radiation possibly by quickly reassembling old genetic variation into new combinations.

Urban Microplastic Pollution Revealed by a Large-Scale Wetland Soil Survey.

Microplastics (MPs), as a new persistent pollutant, can be emitted and accumulated in urban environments, but there is no detailed information on the driving factors of MP pollution. In this study, through a large-scale wetland soil survey, the features of MPs were characterized in each urban area. The results showed an average abundance to be 379 n/kg in wetland soil. Polypropylene, fiber or fragment, and black color were common composition, shape, and color, respectively. The spatial distribution information showed that MP abundance was significantly relevant to the distance from the urban economic center. Furthermore, the correlation and regression analysis revealed that MP abundance was related to soil heavy metal and atmospheric particle (PM10 and PM2.5) concentrations (P < 0.05), while the promotion of socioeconomic activities (urbanization level, population density, etc.) may aggravate the pollution degree. Additionally, by using structural equation modeling, it was found that the urbanization level was the dominant factor driving the MP pollution degree, with a total effect coefficient of 0.49. Overall, this work provides multi-sided environmental information regarding MP pollution in urban ecosystems, which is significant for follow-up studies of MP pollution control and restoration.

Coronary computed tomography angiography study on the relationship between the Ramus Intermedius and Atherosclerosis in the bifurcation of the left main coronary artery.

OBJECTIVE: This study aimed to explore the relationship between the ramus intermedius (RI) and atherosclerosis in the bifurcation of the left coronary artery (LCA). METHODS: Screening patients who underwent CCTA from January to September 2021, 100 patients with RI (RI group) and 100 patients without RI (no-RI group) were randomly enrolled, Evaluation of RI distribution characteristics and left main coronary artery(LM),Left anterior descending branch(LAD),left circumflex branch(LCX) proximal segment plaque distribution, measurement of LAD-LCX bifurcation angle(∠LAD-LCX),Comparison of the three distribution characteristics with the incidence of plaques in the left main trunk bifurcation area (LM, LAD, LCX) between groups and within the RI group. RESULTS: The difference in the incidence of plaques in the proximal LCX and the LM between the RI group and the no-RI group were not statistically significant (P > 0.05). The incidence of plaques in the proximal LAD in the RI group was significantly higher than that in the non-RI group (77% versus 53%, P < 0.05). However, there was no statistically significant difference between the two groups after PSM. A univariate logistic regression analysis revealed that an RI was a risk factor for plaque formation in the proximal LAD (P < 0.001), and a multivariate logistic regression analysis revealed that an RI was not an independent risk factor for plaque formation in the proximal LAD (P > 0.05). When compared within the RI group, the difference in the incidence of plaques in the proximal segment of LAD, the proximal segment of LCX, and the LM among the different distribution groups of RI was not statistically significant, respectively (P > 0.05). CONCLUSION: RI is not an independent risk factor for atherosclerosis in the left coronary artery bifurcation zone, but it may indirectly increase the risk of atherosclerosis in the proximal segment of the LAD.

Antifouling activity of terpenoids from the corals Sinularia flexibilis and Muricella sp. against the bryozoan Bugula neritina.

Marine natural products are promising sources of green antifoulants. Here, a new compound (1) was isolated from the soft coral Sinularia flexibilis. This compound, another nine cembranoids (2-10) from S. flexibilis, and three eunicellin-type diterpenoids (11-13) from the gorgonian Muricella sp. were tested for antifouling activity against larval settlement of the bryozoan Bugula neritina. Compounds 2, 3, 4, 9, 12, and 13 exhibited significant antifouling activity, with EC50 values of 18.2, 99.7, 67.9, 35.6, 33.9, and 49.3 µM, respectively. Analysis of the structure-activity relationships suggested that the hydroxy group at C-13 in compound 4 reduced its antifouling activity.

Myocardial microvascular function assessed by CMR first-pass perfusion in patients treated with chemotherapy for gynecologic malignancies.

OBJECTIVES: Cancer chemotherapy potentially increases the risk of myocardial ischemia. This study assessed myocardial microvascular function by cardiac magnetic resonance (CMR) first-pass perfusion in patients treated with chemotherapy for gynecologic malignancies. METHODS: A total of 81 patients treated with chemotherapy for gynecologic malignancies and 39 healthy volunteers were prospectively enrolled and underwent CMR imaging. Among the patients, 32 completed CMR follow-up, with a median interval of 6 months. The CMR sequences comprised cardiac cine, rest first-pass perfusion, and late gadolinium enhancement. RESULTS: There were no significant differences in the baseline characteristics between the patients and normal controls (all p > 0.05). Compared with the normal controls, the patients had a lower myocardial perfusion index (PI) (13.62 ± 2.01% vs. 12% (11 to 14%), p = 0.001) but demonstrated no significant variation with an increase in the number of chemotherapy cycles at follow-up (11.79 ± 2.36% vs. 11.19 ± 2.19%, p = 0.234). In multivariate analysis with adjustments for clinical confounders, a decrease in the PI was independently associated with chemotherapy treatment (ß = - 0.362, p = 0.002) but had no correlation with the number of chemotherapy cycles (r = - 0.177, p = 0.053). CONCLUSION: Myocardial microvascular dysfunction was associated with chemotherapy treatment in patients with gynecologic malignancies, and can be assessed and monitored by rest CMR first-pass perfusion. KEY POINTS: • Chemotherapy was associated with but did not aggravate myocardial microvascular dysfunction in patients with gynecologic malignancies. • Rest CMR first-pass perfusion is an ideal modality for assessing and monitoring alterations in myocardial microcirculation during chemotherapy treatment.

The effect of preoperative statin treatment on acute kidney injury in elderly patients undergoing valve replacement surgery.

PURPOSES: The effects of preoperative statin treatment on acute kidney injury (AKI) remain controversial, and current clinical evidence regarding statin use in the elderly undergoing valve replacement surgery (VRS) is insufficient. The present study aimed to investigate the association between preoperative statin treatment and AKI after VRS in the elderly. METHODS: Three thousand seven hundred ninety-one elderly patients (≥ 60 years) undergoing VRS were included in this study and divided into 2 groups, according to the receipt of statin treatment before the operation: statin users (n = 894) and non-users (n = 2897). We determined the associations between statin use, AKI, and other adverse events using a multivariate model and propensity score-matched analysis. RESULTS: After propensity score-matched analysis, there was no difference between statin users and non-users in regard to postoperative AKI (72.5% vs. 72.4%, p = 0.954), in-hospital death (5.7% vs. 5.1%, p = 0.650) and 1-year mortality (log-rank = 0, p = 0.986). The multivariate analysis showed that statin use was not an independent risk factor for postoperative AKI (OR = 0.97, 95% CI: 0.90-1.17, p = 0.733), in-hospital mortality (OR = 1.12, 95% CI: 0.75-1.68, p = 0.568), or 1-year mortality (HR = 0.95, 95% CI: 0.70-1.28, p = 0.715). CONCLUSION: Preoperative statin treatment did not significantly affect the risk of AKI among elderly patients undergoing VRS.

The effect of medication on serum anti-müllerian hormone (AMH) levels in women of reproductive age: a meta-analysis.

OBJECTIVE: The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET). METHODS: Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis. RESULTS: After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001). CONCLUSIONS: Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.

L-Cysteine attenuates osteopontin-mediated neuroinflammation following hypoxia-ischemia insult in neonatal mice by inducing S-sulfhydration of Stat3.

We previously show that L-Cysteine administration significantly suppresses hypoxia-ischemia (HI)-induced neuroinflammation in neonatal mice through releasing H2S. In this study we conducted proteomics analysis to explore the potential biomarkers or molecular therapeutic targets associated with anti-inflammatory effect of L-Cysteine in neonatal mice following HI insult. HI brain injury was induced in postnatal day 7 (P7) neonatal mice. The pups were administered L-Cysteine (5 mg/kg) at 24, 48, and 72 h post-HI. By conducting TMT-based proteomics analysis, we confirmed that osteopontin (OPN) was the most upregulated protein in ipsilateral cortex 72 h following HI insult. Moreover, OPN was expressed in CD11b+/CD45low cells and infiltrating CD11b+/CD45high cells after HI exposure. Intracerebroventricular injection of OPN antibody blocked OPN expression, significantly attenuated brain damage, reduced pro-inflammatory cytokine levels and suppressed cerebral recruitment of CD11b+/CD45high immune cells following HI insult. L-Cysteine administration reduced OPN expression in CD11b+/CD45high immune cells, concomitant with improving the behavior in Y-maze test and suppressing cerebral recruitment of CD11b+/CD45high immune cells post-HI insult. Moreover, L-Cysteine administration suppressed the Stat3 activation by inducing S-sulfhydration of Stat3. Intracerebroventricular injection of Stat3 siRNA not only decreased OPN expression, but also reversed HI brain damage. Our data demonstrate that L-Cysteine administration effectively attenuates the OPN-mediated neuroinflammation by inducing S-sulfhydration of Stat3, which contributes to its anti-inflammatory effect following HI insult in neonatal mice. Blocking OPN expression may serve as a new target for therapeutic intervention for perinatal HI brain injury.

Association between complete right bundle branch block and atrial fibrillation development.

BACKGROUND: Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear. METHODS: We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years). CRBBB was defined as a late R (R') wave in lead V1 or V2 with a slurred S wave in lead I and/or lead V6 with a prolonged QRS duration (≥120 ms). RESULTS: Among the 2639 patients, CRBBB was detected in 40 patients (1.5%), and the prevalence of AF was 7.4% (196/2639). The proportion of patients with AF and CRBBB was higher than the proportion of patients with AF without CRBBB (22.5% vs. 7.2%; p = 0.001). In the forward multivariate logistic analysis, CRBBB (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.350-8.211; p = 0.009), complete left bundle branch block (OR, 2.209; 95% CI, 1.238-3.940; p = 0.007), age (OR, 1.020; 95% CI, 1.005-1.035; p = 0.009), valvular heart disease (OR, 2.332; 95% CI, 1.531-3.552; p < 0.001), left atrial diameter (OR, 1.133; 95% CI, 1.104-1.163; p < 0.001), left ventricular ejection fraction (OR, 1.023; 95% CI, 1.006-1.041; p = 0.007), and class I or III anti-arrhythmic drug use (OR, 10.534; 95% CI, 7.090-15.651; p < 0.001) were associated with AF. CONCLUSION: Complete right bundle branch block was significantly associated with AF development in hospitalized patients with cardiovascular diseases.