Mitochondrial Homeostasis Regulating Mitochondrial Number and Morphology Is a Distinguishing Feature of Skeletal Muscle Fiber Types in Marine Teleosts.

Fishes' skeletal muscles are crucial for swimming and are differentiated into slow-twitch muscles (SM) and fast-twitch muscles (FM) based on physiological and metabolic properties. Consequently, mitochondrial characteristics (number and morphology) adapt to each fiber type's specific functional needs. However, the mechanisms governing mitochondrial adaptation to the specific bioenergetic requirements of each fiber type in teleosts remain unclear. To address this knowledge gap, we investigated the mitochondrial differences and mitochondrial homeostasis status (including biogenesis, autophagy, fission, and fusion) between SM and FM in teleosts using Takifugu rubripes as a representative model. Our findings reveal that SM mitochondria are more numerous and larger compared to FM. To adapt to the increased mitochondrial number and size, SM exhibit elevated mitochondrial biogenesis and dynamics (fission/fusion), yet show no differences in mitochondrial autophagy. Our study provides insights into the adaptive mechanisms shaping mitochondrial characteristics in teleost muscles. The abundance and elongation of mitochondria in SM are maintained through elevated mitochondrial biogenesis, fusion, and fission, suggesting an adaptive response to fulfill the bioenergetic demands of SM that rely extensively on OXPHOS in teleosts. Our findings enhance our understanding of mitochondrial adaptations in diverse muscle types among teleosts and shed light on the evolutionary strategies of bioenergetics in fishes.

Chromosome analysis of foetal tissue from 1903 spontaneous abortion patients in 5 regions of China: a retrospective multicentre study.

BACKGROUND: Abnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA. METHODS: A retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age. RESULTS: In our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group. CONCLUSION: The findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion.

In-situ synthesis of non-phase-separated boron carbon nitride for photocatalytic reduction of CO2.

Non-phase-separated hexagonal boron carbon nitride (h-BCN) is an emerging type of promising metal-free photocatalyst, but the synthesis of this material remains quite challenging. Here, h-BCN without phase separation was obtained through a novel organic-inorganic hybrid precursor pyrolysis method using boric acid and ethylenediamine as raw materials. The resultant BCN-1 exhibited excellent photocatalytic activity for CO2 reduction, as confirmed by a CO generation rate of 13.97 µmol g-1 h-1 under visible light illumination with no co-catalyst or sacrificial agent. This rate was 9.4 times higher than that of g-C3N4 (2.1 µmol g-1 h-1) under the same experimental condition. The pre-existing C-N-B bond is essential for mediating the growth kinetics and diminishing the thermodynamically preferred C and BN phase-segregation structure, while ammonia is crucial for C-N-B bond fixation and pore formation during the pyrolysis process. This finding of a facile method for synthesizing non-phase-separated BCN has positive effects on the study of photocatalytic CO2 reduction by sustainable metal-free catalysts.

Hypertension as an independent risk factor for severity and mortality in patients with COVID-19: a retrospective study.

PURPOSE OF THE STUDY: Hypertension is one of the most common comorbidities in COVID-19 pneumonia. However, whether it is an independent factor on the severity and mortality of COVID-19 has not been studied. STUDY DESIGN: In this study, 736 patients with a PCR-confirmed diagnosis of COVID-19 were included from 12 January 2020 to 25 March 2020. All patients were divided into two groups according to whether or not they were hypertensive. After propensity score matching (PSM) to remove the interference of mismatches in the baseline data, the clinical characteristics and outcomes of angiotensin II receptor blocker (ARB)/ACE inhibitors application were analysed. RESULTS: A total of 220 (29.9%) patients were hypertensive, and 516 (70.1%) patients were not hypertensive. PSM eliminated demographic and comorbidity differences between the two groups. Of all participants, 32 patients died (4.3% mortality), including 17 out of 220 in the hypertension group (7.7%) and 15 out of 516 in the non-hypertension group (2.9%). The incidence of intensive care unit (ICU) stay in the hypertension group (12.8%) was higher than in the non-hypertension group (5.3%) (p<0.05). Logistic regression analysis showed that hypertension was an independent risk factor for death, not other comorbidities. Kaplan-Meier analysis showed that mortality was higher in the hypertension group than in the non-hypertension group before and after PSM (p<0.05). There was no statistically significant difference in ICU therapy, mortality and hospitalisation time between hypertensive patients with or without ARBs/ACE inhibitors (p>0.05). CONCLUSION: Hypertension was an independent risk factor for the severity and mortality of patients with COVID-19. ARBs/ACE inhibitors should not be discontinued in hypertensive patients with COVID-19.

Effect of BMP-Wnt-Nodal signal on stem cell differentiation.

The generation of germ cells from embryonic stem cells in vitro has current historical significance. Western blot, qPCR, immunofluorescence and flow cytometry assays were used to investigate the differences in expression levels of totipotency and specific markers for Wnt regulation and the related signalling pathways during primordial germ cell-like cell (PGCLC) induction and differentiation. During PGCLC induction, activation of WNT3a increased the expression of NANOG, SOX2 and OCT4, but Mvh, DAZL, Blimp1, TFAP2C, Gata4, SOX17, EOMES, Brachyury and PRDM1 expression levels were significantly reduced. Inhibition of the WNT signal demonstrated the opposite effect. Similarly, inhibitors of BMP and the Nodal/Activin signal were used to determine the effect of signal pathways on differentiation. CER1 affected the Wnt signal and differentiation, but the inhibitor SB only regulated differentiation. BMP-WNT-NODAL were mainly responsible for regulating differentiation. Our results provide a reliable theoretical basis and feasibility for further clinical medical research.

Electrocardiogram-Based R Wave Pulse Wave Index for Assessment of Carotid Atherosclerosis.

BACKGROUND Carotid atherosclerosis (CA) is a common disease in middle-aged and elderly people, which is closely related to cardiovascular and cerebrovascular disease. In this study, we investigated the benefits of the electrocardiogram (ECG)-based R wave pulse wave index (ERWVI) for the diagnosis of CA. MATERIAL AND METHODS According to CA examinations by color Doppler ultrasound, patients were assigned to positive and negative groups. The ECG R wave-Pulse wave transit time (ERWPTT) was obtained by synchronously collecting ECG signals (R wave in ECG) and the time variations in maximum finger pulse oxygen (DOP) on the ECG monitor. RESULTS ERPWI was positively correlated with sex, age, BMI, diastolic/systolic blood pressure, fasting blood glucose, uric acid, cholesterol and triglyceride levels, LDL-cholesterol, non-alcoholic fatty liver disease (NAFLD), creatinine, and homocysteine, and was negatively correlated with HDL-cholesterol (P<0.05). With the increase of ERPWI, the incidence of CA significantly increased to various degrees among the subgroups (P<0.05). The binary logistic regression model showed that ERPWI was an independent risk factor for atherosclerosis. The ROC curve showed that when ERPWI was above 0.505, the incidence of CA increased significantly. CONCLUSIONS There is a close relationship between ERPWI and CA. ERPWI is an independent risk factor for CA. ERPWI ≥0.505 can be used as a diagnostic threshold for CA and a reference index for the diagnosis of CA.

Establishment of a feeder and serum-free culture system for human embryonic stem cells.

Stem cells are an immortal cell population capable of self-renewal; they are essential for human development and ageing and are a major focus of research in regenerative medicine. Despite considerable progress in differentiation of stem cells in vitro, culture conditions require further optimization to maximize the potential for multicellular differentiation during expansion. The aim of this study was to develop a feeder-free, serum-free culture method for human embryonic stem cells (hESCs), to establish optimal conditions for hESC proliferation, and to determine the biological characteristics of the resulting hESCs. The H9 hESC line was cultured using a homemade serum-free, feeder-free culture system, and growth was observed. The expression of pluripotency proteins (OCT4, NANOG, SOX2, LIN28, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) in hESCs was determined by immunofluorescence and western blotting. The mRNA expression levels of genes encoding nestin, brachyury and α-fetoprotein in differentiated H9 cells were determined by RT-PCR. The newly developed culture system resulted in classical hESC colonies that were round or elliptical in shape, with clear and neat boundaries. The expression of pluripotency proteins was increased, and the genes encoding nestin, brachyury, and α-fetoprotein were expressed in H9 cells, suggesting that the cells maintained in vitro differentiation capacity. Our culture system containing a unique set of components, with animal-derived substances, maintained the self-renewal potential and pluripotency of H9 cells for eight passages. Further optimization of this system may expand the clinical application of hESCs.

[Association of abnormal length of Y chromosome with semen quality and outcome of assisted reproductive technology in humans].

OBJECTIVE: To investigate the association of the abnormal length of human Y chromosome with semen quality and the outcome of assisted reproductive technology (ART). METHODS: Based on the karyotype, we assigned the patients undergoing ART to a normal control, a long Y chromosome (Y>18), and a short Y chromosome group (Y<22). We compared the semen parameters and numbers of embryos and high-quality embryos among the three groups of patients and performed statistical analysis of the obtained data using Chi-square distribution and t-test. RESULTS: Compared with the control, the Y>18 group showed a significantly lower incidence rate of asthenozoospermia (31.03% vs 8.33%, P <0.05) and a larger number of high-quality embryos (5.46 ± 4.54 vs 7.40 ± 5.49, P<0.05). Both the incidence rate of azoospermia and number of total embryos were remarkably lower in the control than in the Y<22 group (1.87% vs 16.47%, P <0.05; 8.60 ± 7.03 vs 10.00 ± 6.58, P<0.05). No statistically significant differences were found in the pregnancy rate between the Y>18 and Y<22 groups (P>0.05). CONCLUSIONS: Short Y chromosome may affect spermatogenesis, but the length of Y chromosome does not negatively influence the outcome of ART.

[Influence of basic thyroid-stimulating hormone levels on outcomes of IVF/ICSI in Qinghai].

OBJECTIVE: To study basic thyroid stimulating hormone (bTSH) levels impact on outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in Qinghai. METHODS: Totally 282 cases with IVF cycles and 93 cases with ICSI cycles were studied prospectively, according to bTSH level, patients were divided into four groups. Reproduction rate, clinical pregnancy rate, miscarriage rate and live birth rate were studied among four groups. RESULTS: (1) In 375 cases with IVF/ICSI cycles, bTSH was positively correlated with abortion rate (r = 0.42, P = 0.04), but live birth rate and growing rate showed negative correlations with bTSH (r = -0.42, -0.28; P = 0.04, 0.03). bTSH and the number of eggs, the number of fertilized eggs, the number of embryos, biochemical pregnancy rate, and clinical pregnancy rate were no significant correlation (all P > 0.05). (2) Among women at group of ≤ 1.7, >1.7 and ≤ 2.5, >2.5 and ≤ 3.5, >3.5 mU/L, the implantation rates were 28.7%, 27.3%, 37.7% and 19.2%, live birth rates were 80.9%, 75.0%, 82.7%, and 59.8%, abortion rates were 19.0%, 15.0%, 16.7%, 40.1%; they all showed significant difference (all P < 0.05). Abortion rate in women with high bTSH level was higher than that of women with lower bTSH level, however implantation rate, live birth rate in women with high bTSH level were lower. CONCLUSION: When bTSH level is >3.5 mU/L, the abortion rate were increased, but live birth rate, rate of implantation were decreased.

Predicting risk of subsequent pregnancy loss among women with recurrent pregnancy loss: An immunological factor-based multivariable model.

PROBLEM: Studies on subsequent pregnancy loss prediction models specific for recurrent pregnancy loss (RPL) patients are very limited. This study aims to develop a risk predictive model based on the immunological parameters for the subsequent pregnancy loss risk in northwest Chinese RPL patients. METHOD OF STUDY: Totally of 357 RPL patients recruited from Lanzhou University Second Hospital were included in this retrospective study. Univariate analysis was performed on RPL patients with outcomes of live birth or pregnancy loss. Subsequently, the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables among baseline and clinical characteristics and to develop a pregnancy loss risk prediction model with all 357 RPL patients. The area under the curve (AUC), calibration curve and decision curve analyses were used to evaluate the performance of the prediction model; moreover, 10-fold cross-validation was used for internal validation. RESULTS: Ten factors of maternal age, age of menarche, previous pregnancy loss, IL-10, complement 4, IgA, antiprothrombin antibody IgG/IgM, rheumatoid factor IgA, and lupus anticoagulant (LA) 1/LA2 ratio were finally selected as variables for the prediction model of pregnancy loss risk. The AUC value and Hosmer-Lemeshow test p-value of the model were .707 and .599, respectively, indicating a satisfactory discrimination and calibration performance. Moreover, the clinical decision curve suggested this prediction model have a good positive net benefit. CONCLUSIONS: This is the first prediction model for the risk of subsequent pregnancy loss in northwest Chinese women with RPL, providing a user-friendly tool to clinicians for the early prediction and timely management of RPL patients.

Preconception Non-criteria Antiphospholipid Antibodies and Risk of Subsequent Early Pregnancy Loss: a Retrospective Study.

The aim of this study was to investigate the subsequent early pregnancy outcomes in women positive for non-criteria antiphospholipid antibodies (NC-aPLs) before pregnancy. A total of 273 patients who had experienced sporadic or recurrent pregnancy loss and had been screened for 13 NC-aPLs at preconception were recruited in this study from September 2019 to February 2022. Serum levels of NC-aPLs were measured by ELISA using specific kits. The primary outcome was early pregnancy loss, and the secondary outcomes were biochemical pregnancy, clinically confirmed pregnancy loss, and ongoing pregnancy. Among these subjects, 56 patients had one previous pregnancy loss, and 217 had recurrent pregnancy loss (RPL). The NC-aPLs (+) and NC-aPLs (-) groups had similar rates of early pregnancy loss (EPL) after adjustment, regardless of the number of positive NC-aPLs (aOR = 1.054, 95% CI 0.602-1.846). Other outcomes were comparable in both groups, including the rates of biochemical pregnancy (aOR = 1.344, 95% CI 0.427-4.236), clinically confirmed pregnancy loss (aOR = 0.744, 95% CI 0.236-2.344), and ongoing pregnancy (aOR = 0.949, 95% CI 0.542-1.660). Based on sensitivity analysis, the NC-aPLs (+) were not associated with adverse early pregnancy outcomes in women with RPL. Furthermore, the difference in gestational weeks of pregnancy loss between the two groups was also insignificant. This study found no evidence linking preconception NC-aPL positivity to early pregnancy outcomes but offers a reference for future research to clarify NC-aPLs' potential clinical impact.

High serum copper as a risk factor of all-cause and cause-specific mortality among US adults, NHANES 2011-2014.

Background: Several studies have shown that serum copper levels are related to coronary heart disease, diabetes, and cancer. However, the association of serum copper levels with all-cause, cause-specific [including cardiovascular disease (CVD) and cancer] mortality remains unclear. Objectives: This study aimed to prospectively examine the association of copper exposure with all-cause, CVD, and cancer mortality among US adults. Methods: The data for this analysis was obtained from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. Mortality from all-causes, CVD, and cancer mortality was linked to US National Death Index mortality data. Cox regression models were used to estimate the association between serum copper levels and all-cause, CVD, and cancer mortality. Results: A total of 2,863 adults were included in the main study. During the mean follow-up time of 81.2 months, 236 deaths were documented, including 68 deaths from cardiovascular disease and 57 deaths from cancer. The weighted mean overall serum copper levels was 117.2 ug/L. After adjusting for all of the covariates, compared with participants with low (1st tertile, <103 µg/L)/medium (2st tertile, 103-124 µg/L) serum copper levels, participants with high serum copper levels (3rd tertile, ≥124 µg/L) had a 1.75-fold (95% CI, 1.05-2.92)/1.78-fold (1.19,2.69) increase in all-cause mortality, a 2.35-fold (95% CI, 1.04-5.31)/3.84-fold (2.09,7.05) increase in CVD mortality and a 0.97-fold (95% CI, 0.28-3.29)/0.86-fold (0.34,2.13) increase in cancer mortality. In addition, there was a linear dose-response association between serum copper concentration with all-cause and CVD mortality (P for nonlinear > 0.05). Conclusions: This prospective study found that serum copper concentrations were linearly associated with all-cause and CVD mortality in US adults. High serum copper levels is a risk factor for all-cause and CVD mortality.

The safety and efficacy of tumor necrosis factor-alpha inhibitor on pregnancy outcomes in patients with unexplained recurrent miscarriage.

OBJECTIVES: Although tumor necrosis factor-alpha inhibitor (TNFi) treatment may improve pregnancy outcomes in unexplained recurrent miscarriage (URM) patients, evidence for its efficacy and safety is still insufficient. The goal of this study was to evaluate the efficacy and safety of TNFi on pregnancy outcomes in patients with URM. METHODS: This retrospective study was conducted at a single institution in China, involving 121 patients treated with TNFi for URM from 2019 to 2022. Patients enrolled were divided into treatment group (receiving TNFi and heparin therapy) and control group (receiving heparin therapy). The outcome variables were the 24-week live birth rate, miscarriage rate, ectopic pregnancy rate, neonatal outcomes, and adverse events. RESULTS: In our study, patients receiving TNFi treatment exhibited a significant increase in live birth rates, achieving 71.2 % compared to the 50.9 % observed in the control group (OR 2.507, 95 % CI: 1.127-5.579). Concurrently, there was a discernible reduction in the miscarriage rate within the TNFi-treated group, marking 24.2 %, in contrast to 43.6 % in the control group (OR 0.387, 95 % CI: 0.170-0.884). Subgroup analyses further illuminated that those under the age of 35 benefitted remarkably from TNFi treatment, with live birth rates soaring to 62.5 % (OR 2.525, 95 % CI: 1.041-6.125). For patients with a history of two miscarriages, the TNFi regimen significantly augmented the live birth rate to 58.9 % (OR 3.044, 95 % CI: 1.039-8.921). Patients with a normal weight range registered a 58.4 % live birth rate post-TNFi treatment (OR 4.261, 95 % CI: 1.539-11.397). Notably, an evident interaction between BMI and TNFi treatment was identified, suggesting a potential modulatory role of BMI on the therapeutic efficacy of TNFi. About safety assessments, neither the TNFi-treated group nor the control manifested any significant disparities in liver function abnormalities, platelet count anomalies, or other pregnancy-related complications. CONCLUSIONS: TNFi, alongside basic therapy, notably enhances the live birth rate in URM patients under 35, with two prior miscarriages or a normal BMI, without increasing adverse event risk. Further prospective studies are essential to validate these observations.

A predictive model of pregnancy loss using pre-pregnancy endocrine and immunological parameters in women with abnormal glucose/lipid metabolism and previous pregnancy loss.

OBJECTIVE: To investigate the clinical and endocrine risk factors for pregnancy loss in women with abnormal glucose/lipid metabolism and a history of pregnancy loss, and to develop a predictive model to assess the risk of pregnancy loss in these women's subsequent pregnancies. METHODS: Patients with a history of pregnancy loss who had abnormal glucose/lipid metabolism were retrospectively included in this study, and their pre-pregnancy baseline and clinical characteristics were collected. A predictive nomogram was constructed based on the results of the multivariable logistic regression model analysis, and its calibration and discriminatory capabilities were evaluated. The internal validation was then performed and the net benefits were assessed by the clinical decision curve. RESULTS: The predictive model was eventually incorporated eight variables, including maternal age, previous pregnancy losses, anticardiolipin antibody (aCL) IgG, aCL IgM, thyroid peroxidase antibody, complement 4, free thyroxine and total cholesterol. The area under the curve (AUC) of the nomogram was 0.709, and Chi-square value and P value of the Hosmer-Lemeshow test were 12.786 and 0.119, respectively, indicating that the nomogram had a satisfactory calibration and discriminatory performance. The validation cohort showed a similar result for the discrimination of the nomogram (AUC = 0.715). The clinical decision curve demonstrated the nomogram had good positive net benefits. CONCLUSIONS: This is the first study to predict the risks of subsequent pregnancy loss in women with abnormal glucose/lipid metabolism and history of pregnancy loss using pre-pregnancy clinical and endocrine parameters. This predictive nomogram may provide clinicians assistance to personalize the management of subsequent pregnancies in these patients.

A bibliometric and visualization analysis of global research status and frontiers on autophagy in cardiomyopathies from 2004 to 2023.

BACKGROUND: Autophagy is intimately associated with the development of cardiomyopathy, and has received widespread attention in recent years. However, no relevant bibliometric analysis is reported at present. In order to summarize the research status of autophagy in cardiomyopathy and provide direction for future research, we conducted a comprehensive, detailed, and multidimensional bibliometric analysis of the literature published in this field from 2004 to 2023. METHODS: All literatures related autophagy in cardiomyopathy from 2004 to 2023 were collected from the Web of Science Core Collection (WOSCC), and annual papers, global publication trends and proportion charts were analyzed and plotted using Graphpad price v8.0.2. In addition, CtieSpace (6.2.4R (64 bit) Advanced Edition) and VOSviewer (1.6.18 Edition) were used to analyze and visualize these data. RESULTS: 2279 papers about autophagy in cardiomyopathy were accessed in the WoSCC over the last 20 years, comprising literatures from 70 countries and regions, 2208 institutions, and 10,810 authors. China contributes 56.32% of the total publications, substantially surpassing other countries, while the U.S. is ranked first in frequency of citations. Among the top 10 authors, 6 are from China and 4 are from the United States. Air Force Military Medical University was the institution with the highest number of publications; while journal of molecular and cellular cardiology (62 articles, 2.71% of the total) was the journal with the highest number of papers published in the field. Clustering of co-cited references and temporal clustering analysis showed that ferroptosis, hydrogen sulfide mitophagy, lipid peroxidation, oxidative stress, and SIRT-1 are hot topics and trends in the field. The principal keywords are oxidative stress, heart and heart-failure. CONCLUSION: The research on autophagy in cardiomyopathy is in the developmental stage. This represents the first bibliometric analysis of autophagy in cardiomyopathy , revealing the current research hotspots and future research directions in this field.

pH-triggered self-assembly of biocompatible histamine-functionalized triblock copolymers.

Histamine functionalized poly(allyl glycidyl ether)-b-poly(ethylene glycol)-b-poly(allyl glycidyl ether) (PAGE-PEO-PAGE) triblock copolymers represent a new class of physically cross-linked, pH-responsive hydrogels with significant potential for biomedical applications. These telechelic triblock copolymers exhibited abrupt and reversible hydrogelation above pH 7.0 due to a hudrophilic/hydrophobic transition of the histamine units to form a network of hydrophobic domains bridged by a hydrophilic PEO matrix. These hydrophobic domains displayed improved ordering upon increasing pH and self-assembled into a body centered cubic lattice at pH 8.0, while at lower concentrations formed well-defined micelles. Significantly, all materials were found to be non-toxic when evaluated on three different cell lines and suggests a range of medical and biomedical applications.

L-type Ca2+ channel blocker attenuates impairment induced by acidosis in hippocampal neurons.

Accumulation of acid in the brain during ischemia may contribute to the activation of voltage-gated Ca2+ channels and subsequent neuronal injury. However, information regarding the role of L-type Ca2+ channel under acidosis remains unclear. In the present study, we examined the role of L-type Ca2+ channel in acidosis induced neuronal death and subsequent pathogenesis events responsible for neuron degeneration. Here we report that preincubation of cells with nifedipine (5 microM, 10 microM), an inhibitor of L-type Ca2+ channel markedly reduced neuronal death induced by moderate extracellular acidosis (pH 6.5) on cultured hippocampus neurons. Furthermore, nifedipine decreased the hippocampus neuronal swelling, as well as the accumulation of Ca2+ and collapse of mitochondrial membrane potential induced by acidosis. These findings demonstrate that pharmacological inhibition of L-type Ca2+ channel would attenuate neuronal degeneration caused by toxic low pH exposure in rat hippocampus neuron.

Efficacy and safety of recombinant human granulocyte colony-stimulating factor in patients with poor ovarian response: protocol for a multicentre, randomised, controlled trial.

INTRODUCTION: Approximately 17.5% of couples of reproductive age have experienced infertility. Women with a poor ovarian response (POR) must undergo in vitro fertilisation (IVF) and embryo transfer to achieve pregnancy. However, studies have reported a poor response to gonadotropin stimulation in women undergoing IVF-ET. Results from animal experiments suggest that granulocyte colony-stimulating factor (G-CSF) has a curative effect by protecting ovarian function, reducing follicle loss and delaying premature ovarian failure in rats caused by chemotherapy. Clinical studies on the therapeutic effect of G-CSF are deficient; therefore, this study will investigate its ability to improve ovum quality and maturity among women with POR undergoing IVF/intracytoplasmic sperm injection (ICSI). METHODS AND ANALYSIS: This clinical, multicentre, triple-blind, placebo-controlled trial will employ balanced randomisation (1:1). The planned sample size is 312 participants (156 subjects in each group). A total of 312 patients with infertility undergoing IVF/ICSI will be recruited from four public hospitals in China. The participants will be randomly divided into an experimental group (G-CSF) and a placebo group (control). All patients will be treated by using the progestin-primed ovarian stimulation superovulation protocol. The primary outcome will be D3 embryo quality. The number of ova obtained, MII ova and transferable embryos will be inclusive in the secondary outcome. ETHICS AND DISSEMINATION: To our knowledge, this is the first clinical trial to investigate the effect of G-CSF treatment timing and stimulation protocol in patients with POR in China. This study will provide new information about G-CSF efficacy among patients with POR undergoing IVF/ICSI and can help improve ovum quality and maturity. Clinical trials on this subject are deficient in China; therefore, a well-designed randomised trial is needed to determine the ability of G-CSF to improve ovum quality and maturity to facilitate conception among women with POR treated with IVF/ICSI. TRIAL REGISTRATION NUMBER: ChiCTR2200062412.

Efficacy and safety of recombinant human granulocyte colony-stimulating factor in patients with unexplained recurrent spontaneous abortion: A systematic review and meta-analysis.

INTRODUCTION: Published data regarding efficacy of intrauterine perfusion of recombinant human granulocyte colony-stimulating factor for patients with unexplained recurrent spontaneous abortion (URSA) is inconclusive. This study aims at evaluating the efficacy and safety of G-CSF in URSA. MATERIALS AND METHODS: Electronic databases were searched including Cochrane Library, PubMed, Embase, China Biology Medicine disc, China Science and Technology Journal Database, Wanfang Database and China National Knowledge Infrastructure Database (last search was performed on Sep 10th, 2022). A systematic review and meta-analysis was conducted with R-language software. Combined relative risk (RRs), and 95% confidence intervals (CIs) were calculated to estimate efficacy and safety. RESULTS: Compared with placebo, the efficacy of G-CSF in the treatment of URSA patients was significant in conception rate (RR=1.34, 95%CI: 1.03-1.74, P = 0.028), and was none of significance in live birth rate (RR=1.35, 95%CI: 0.99-1.84, P = 0.06). Subgroup analysis showed that the ovulation-period-medication was the protective factor for conception rate, while "Ethnicity Asian" and "ovulation-period medication" were the protective factors for live birth rate. When it comes to the safety of rhG-CSF on URSA, meta-analysis showed that rhG-CSF had no significant effect on the incidence of adverse events (AEs) (RR=1.13, 95% CI: 0.89-1.43, P = 0.322), and subgroup analysis showed that the incidence of AEs in each subgroup did not increase significantly (P > 0.05). CONCLUSION: Based on our meta-analysis, intrauterine perfusion of rhG-CSF in ovulation period is an effective and safe way to improve conception rate in URSA.

Prevalence of Chronic Kidney Disease Among US Adults With Hypertension, 1999 to 2018.

BACKGROUND: Hypertension is a major cause of end-stage renal disease. Assessing temporal trends in the prevalence of chronic kidney disease (CKD) in hypertension could provide information for public health policies and plans. METHODS: From the National Health and Nutrition Examination Survey from 1999 to 2018, a probability sample of adults aged ≥20 years was collected. The primary outcomes were classified according to the estimated glomerular filtration rate and urinary albumin. Trend tests were performed to assess age-standardized prevalence trends of CKD, albuminuria, and macroalbuminuria in US adults with hypertension. RESULTS: A total of 23 120 US adults with hypertension were included in this study. The prevalence of any CKD, albuminuria, or macroalbuminuria in hypertension remained relatively stable. However, the age-standardized prevalence of stage 1 CKD in hypertension increased from 4.9% in 2003 to 2006 to 7.0% in 2015 to 2018 (P=0.0077 for trend). The age-standardized prevalence of stage 3b CKD in hypertension decreased from 2.9% in 2011 to 2014 to 2.1% in 2015 to 2018 (P=0.0350 for trend). A similar trend was observed for the age-standardized prevalence of stages 3 to 5 CKD in hypertension, which declined from 10.9% in 2011 to 2014 to 8.9% in 2015 to 2018 (P=0.0160 for trend). CONCLUSIONS: Among US adults with hypertension, the prevalence of any CKD, albuminuria, and macroalbuminuria remained relatively stable from 1999 to 2018, whereas the hypertensive population showed an increasing trend in stage 1 CKD from 2003 to 2006 to 2015 to 2018 and a decreasing trend in the prevalence of stages 3 to 5 and 3b CKD from 2011 to 2014 to 2015 to 2018.