Assessment of HMGB1 and NLRP3 in Determining Efficacy and Prognosis in Hemodialysis Patients with Chronic Renal Failure.

Background: In chronic renal failure (CRF), evaluating treatment efficacy and predicting prognosis is crucial. High Mobility Group Protein B1 (HMGB1) and Nod-like Receptor Protein 3 (NLRP3) were chosen as key markers in chronic renal failure to elucidate their roles in treatment response and prognosis, offering potential insights for enhancing patient care strategies. Objective: This study aims to analyze the clinical impact of HMGB1 and NLRP3 in patients with CRF undergoing hemodialysis. We investigated the relationship between HMGB1 and NLRP3 levels, the efficacy of hemodialysis treatment, and the prognosis for one-year survival. Methods: An observational study was conducted. The study included 62 CRF patients (Group A) admitted to our hospital from May 2020 to August 2022, and 40 healthy individuals undergoing routine medical check-ups during the same period (Group B). We compared the levels of HMGB1 and NLRP3 in the peripheral blood of Group A and Group B. Furthermore, we assessed changes in HMGB1 and NLRP3 before and after hemodialysis in CRF patients to evaluate treatment efficacy and prognostic indicators for one-year survival. Results: Group A exhibited significantly lower HMGB1 expression and higher NLRP3 expression compared to Group B. ROC curve analysis demonstrated that the areas under the curve (AUCs) for HMGB1 and NLRP3 in predicting effective hemodialysis for CRF were 0.884 (95% CI: 0.800-0.968) and 0.721 (95% CI: 0.594-0.848), respectively. The AUCs for HMGB1 and NLRP3 in predicting death from CRF were 0.885 (95% CI: 0.804-0.967) and 0.935 (95% CI: 0.875-0.995), respectively. Conclusions: Both HMGB1 and NLRP3 levels serve as valuable indicators for assessing the efficacy and prognosis of CRF patients undergoing hemodialysis.

Regulating the Active Sites of Metal-Phthalocyanine at the Molecular Level for Efficient Water Electrolysis: Double Deciphering of Electron-Withdrawing Groups and Bimetallic.

Implementing a molecular modulation strategy for metallic phthalocyanines (MPc) without losing the activity of the metal center and inducing a multifunction characteristic in electrocatalytic remains a challenge. Herein, a series of 2D CuCo bimetallic polymerized phthalocyanine modified with strong electron-withdrawing groups (CuCoPc-g, g = F, Cl, Br, NO2 ) for water oxidation in the alkaline electrolyte is designed and simply synthesized. The experimental results testify that the bimetallic design can perform electronic adjustment once and introduce the second active sites to get bifunctional characteristics, and then the electronic structure of the active center can be regulated by electron-withdrawing groups for a second time to achieve the optimal state. These electrons that transfer in the active center of inner metal can generate space-charged regions and the design of the polymer can stabilize active site region to maintain long-term electrolytic stability and high activity. This study precisely regulates the electronic structure of MPc at the molecular level and provides insight into the multifunctional design of polymeric macrocyclic electrocatalysts.

Efficient Suppression of Dendrites and Side Reactions by Strong Electrostatic Shielding Effect via the Additive of Rb2 SO4 for Anodes in Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) have attracted considerable attention due to their low cost and environmental friendliness. However, the rampant dendrite growth and severe side reactions during plating/stripping on the surface of zinc (Zn) anode hinder the practicability of AZIBs. Herein, an effective and non-toxic cationic electrolyte additive of Rb2 SO4 is proposed to address the issues. The large cation of Rb+ is preferentially adsorbed on the surface of Zn metal to induce a strong shielding effect for realizing the lateral deposition of Zn2+ ions along the Zn surface and isolating water from Zn metal to effectively inhibit side reactions. Consequently, the Zn||Zn symmetric cell with the addition of 1.5 mm Rb2 SO4 can cycle more than 6000 h at 0.5 mA cm-2 /0.25 mAh cm-2 , which is 20 times longer than that without Rb2 SO4 . Besides, the Zn||Cu asymmetric cell with Rb2 SO4 achieves a very high average Coulombic efficiency of 99.16% up to 500 cycles. Moreover, the electrolyte with Rb2 SO4 well matches with the VO2 cathode, achieving high initial capacity of 412.7 mAh g-1 at 5 A g-1 and excellent cycling stability with a capacity retention of 71.6% at 5 A g-1 after 500 cycles for the Zn//VO2 full cell.

Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma.

Head and Neck cancers (HNC) are a heterogeneous group of upper aero-digestive tract cancer and account for 931,922 new cases and 467,125 deaths worldwide. About 90% of these cancers are of squamous cell origin (HNSCC). HNSCC is associated with excessive tobacco and alcohol consumption and infection with oncogenic viruses. Genotyping tumour tissue to guide clinical decision-making is becoming common practice in modern oncology, but in the management of patients with HNSCC, cytopathology or histopathology of tumour tissue remains the mainstream for diagnosis and treatment planning. Due to tumour heterogeneity and the lack of access to tumour due to its anatomical location, alternative methods to evaluate tumour activities are urgently needed. Liquid biopsy approaches can overcome issues such as tumour heterogeneity, which is associated with the analysis of small tissue biopsy. In addition, liquid biopsy offers repeat biopsy sampling, even for patients with tumours with access limitations. Liquid biopsy refers to biomarkers found in body fluids, traditionally blood, that can be sampled to provide clinically valuable information on both the patient and their underlying malignancy. To date, the majority of liquid biopsy research has focused on blood-based biomarkers, such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and circulating microRNA. In this review, we will focus on ctDNA as a biomarker in HNSCC because of its robustness, its presence in many body fluids, adaptability to existing clinical laboratory-based technology platforms, and ease of collection and transportation. We will discuss mechanisms of ctDNA release into circulation, technological advances in the analysis of ctDNA, ctDNA as a biomarker in HNSCC management, and some of the challenges associated with translating ctDNA into clinical and future perspectives. ctDNA provides a minimally invasive method for HNSCC prognosis and disease surveillance and will pave the way in the future for personalized medicine, thereby significantly improving outcomes and reducing healthcare costs.

Geographical origin of Plasmodium vivax in the Hainan Island, China: insights from mitochondrial genome.

BACKGROUND: Hainan Province, China, has been an endemic region with high transmission of Plasmodium falciparum and Plasmodium vivax. Indigenous malaria caused by P. vivax was eliminated in Hainan in 2011, while imported vivax malaria remains. However, the geographical origin of P. vivax cases in Hainan remains unclear. METHODS: Indigenous and imported P. vivax isolates (n = 45) were collected from Hainan Province, and the 6 kb mitochondrial genome was obtained. Nucleotide (π) and haplotype (h) diversity were estimated using DnaSP. The numbers of synonymous nucleotide substitutions per synonymous site (dS) and nonsynonymous nucleotide substitutions per nonsynonymous site (dN) were calculated using the SNAP program. Arlequin software was used to estimate the genetic diversity index and assess population differentiation. Bayesian phylogenetic analysis of P. vivax was performed using MrBayes. A haplotype network was generated using the NETWORK program. RESULTS: In total, 983 complete mitochondrial genome sequences were collected, including 45 from this study and 938 publicly available from the NCBI. Thirty-three SNPs were identified, and 18 haplotypes were defined. The haplotype (0.834) and nucleotide (0.00061) diversity in the Hainan populations were higher than China's Anhui and Guizhou population, and the majority of pairwise FST values in Hainan exceeded 0.25, suggesting strong differentiation among most populations except in Southeast Asia. Most Hainan haplotypes were connected to South/East Asian and China's others haplotypes, but less connected with populations from China's Anhui and Guizhou provinces. Mitochondrial lineages of Hainan P. vivax belonged to clade 1 of four well-supported clades in a phylogenetic tree, most haplotypes of indigenous cases formed a subclade of clade 1, and the origin of seven imported cases (50%) could be inferred from the phylogenetic tree, but five imported cases (42.8%) could not be traced using the phylogenetic tree alone, necessitating epidemiological investigation. CONCLUSIONS: Indigenous cases in Hainan display high genetic (haplotype and nucleotide) diversity. Haplotype network analysis also revealed most haplotypes in Hainan were connected to the Southeast Asian populations and divergence to a cluster of China's other populations. According to the mtDNA phylogenetic tree, some haplotypes were shared between geographic populations, and some haplotypes have formed lineages. Multiple tests are needed to further explore the origin and expansion of P. vivax populations.

Activation of Wnt/ß-catenin pathway mitigates blood-brain barrier dysfunction in Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder that causes age-dependent neurological and cognitive declines. The treatments for Alzheimer's disease pose a significant challenge, because the mechanisms of disease are not being fully understood. Malfunction of the blood-brain barrier is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease, especially at the early stages of the disease. However, the underlying mechanisms remain poorly characterized, while few molecules can directly target and improve blood-brain barrier function in the context of Alzheimer's disease. Here, we showed dysfunctional blood-brain barrier in patients with Alzheimer's disease reflected by perivascular accumulation of blood-derived fibrinogen in the hippocampus and cortex, accompanied by decreased tight junction proteins Claudin-5 and glucose transporter Glut-1 in the brain endothelial cells. In the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, blood-brain barrier dysfunction started at 4 months of age and became severe at 9 months of age. In the cerebral microvessels of APP/PS1 mice and amyloid-ß-treated brain endothelial cells, we found suppressed Wnt/ß-catenin signalling triggered by an increase of GSK3ß activation, but not an inhibition of the AKT pathway or switching to the Wnt/planar cell polarity pathway. Furthermore, using our newly developed optogenetic tool for controlled regulation of LRP6 (upstream regulator of the Wnt signalling) to activate Wnt/ß-catenin pathway, blood-brain barrier malfunction was restored by preventing amyloid-ß-induced brain endothelial cells impairments and promoting the barrier repair. In conclusion, targeting LRP6 in the Wnt/ß-catenin pathway in the brain endothelium can alleviate blood-brain barrier malfunction induced by amyloid-ß, which may be a potential treatment strategy for Alzheimer's disease.

Immobilization of M3 Muscarinic Receptor to Rapidly Analyze Drug-Protein Interactions and Bioactive Components in a Natural Plant.

Despite its increasing application in pursing potential ligands, the capacity of receptor affinity chromatography is greatly challenged as most current research studies lack a comprehensive characterization of the ligand-receptor interaction, particularly when simultaneously determining their binding thermodynamics and kinetics. This work developed an immobilized M3 muscarinic receptor (M3R) affinity column by fixing M3R on amino polystyrene microspheres via the interaction of a 6-chlorohexanoic acid linker with haloalkane dehalogenase. The efficiency of the immobilized M3R was tested by characterizing the binding thermodynamics and kinetics of three known drugs to immobilized M3R using a frontal analysis and the peak profiling method, as well as by analyzing the bioactive compounds in Daturae Flos (DF) extract. The data showed that the immobilized M3R demonstrated good specificity, stability, and competence for analyzing drug-protein interactions. The association constants of (-)-scopolamine hydrochloride, atropine sulfate, and pilocarpine to M3R were determined to be (2.39 ± 0.03) × 104, (3.71 ± 0.03) × 104, and (2.73 ± 0.04) × 104 M-1, respectively, with dissociation rate constants of 27.47 ± 0.65, 14.28 ± 0.17, and 10.70 ± 0.35 min-1, respectively. Hyoscyamine and scopolamine were verified as the bioactive compounds that bind to M3R in the DF extract. Our results suggest that the immobilized M3R method was capable of determining drug-protein binding parameters and probing specific ligands in a natural plant, thus enhancing the effectiveness of receptor affinity chromatography in diverse stages of drug discovery.

From Triboelectric Nanogenerator to Multifunctional Triboelectric Sensors: A Chemical Perspective toward the Interface Optimization and Device Integration.

Triboelectric nanogenerators (TENGs) have intrigued scientists for their potential to alleviate the energy shortage crisis and facilitate self-powered sensors. Triboelectric interfaces containing triboelectric functionalized molecular groups and tunable surface charge densities are important for improving the electrical output capability of TENGs and the versatility of future electronics. In this review, following an introduction to the fundamental progress of TENG systems for mechanic energy harvesting, surface modifications that aim to increase the surface charge density and functionality are highlighted, with an emphasis on interfacial chemical modification and triboelectric energetics/dynamics optimization for efficient electrostatic induction and charge transfer. Recent advances in assemblies of multifunctional triboelectric sensing are briefly introduced, and future challenges and chemical perspectives in the field of TENG-based electronics are concisely reviewed. This review presents and advances the understanding of the state-of-the-art chemical strategies toward rational triboelectric interface engineering and system assembly and is expected to guide the rational design of highly efficient and versatile triboelectric sensing.

Copper Hexacyanoferrate Solid-State Electrolyte Protection Layer on Zn Metal Anode for High-Performance Aqueous Zinc-Ion Batteries.

Zinc (Zn) metal possesses broad prospects as an anode for aqueous zinc-ion batteries (AZIBs) due to its considerable theoretical capacity of 820 mAh g-1 . However, the Zn anode suffers from dendrite growth and side reactions during Zn stripping/plating. Herein, a Prussian blue analog of copper hexacyanoferrate (CuHCF) with a 3D open structure and rich polar groups (CN) is coated on Zn foil as a solid-state electrolyte (SSE) protection layer to protect the Zn anode. The CuHCF protection layer possesses low activation energy of 26.49 kJ mol-1 , the high ionic conductivity of 7.6 mS cm-1 , and a large Zn2+ transference number of 0.74. Hence, the Zn@CuHCF||Zn@CuHCF symmetric cell delivers high cycling stability over 1800 h at 5 mA cm-2 , an excellent depth of discharge of 51.3%, and the accumulative discharge capacity over 3000 mAh cm-2 . In addition, the Zn//Ti@CuHCF asymmetric cell achieves the coulombic efficiency (CE) of 99.87% after 2000 cycles. More importantly, the Zn@CuHCF//V2 O5 full cell presents outstanding capacity retention of 87.6% at 10 A g-1 after 3000 cycles. This work develops a type of material to form an artificial protection layer for high-performance AZIBs.

A metabolomic study on the effect of prenatal exposure to Benzophenone-3 on spontaneous fetal loss in mice.

Benzophenone-3 (BP-3) is widely used in a variety of cosmetics and is prevalent in drinking water or food, and women were under notable high exposure burden of BP-3. Reports show the associations between prenatal exposure to BP-3 and the risk of fetal loss, but its underlying mechanism remains largely unknown. Pregnant ICR mice were gavaged with BP-3 from gestational day (GD) 0 to GD 6 at doses of 0.1, 10 and 1000 mg/kg/day. The samples were collected on GD 12. Ultra-performance liquid chromatography coupled with mass spectrometry-based metabolomics was used to detect metabolome changes in fetal mice, the uterus and the placenta to identify the underlying mechanism. The results showed that the body weight and relative organ weights of the liver, brain and uterus of pregnant mice were not significantly changed between the control group and the treatment group. BP-3 increased fetal loss, and induced placental thrombosis and tissue necrosis with enhancement of platelet aggregation. Metabolomic analysis revealed that fructose and mannose metabolism, the TCA cycle, arginine and proline metabolism in the fetus, arginine and proline metabolism and biotin metabolism in the uterus, and arginine biosynthesis and pyrimidine metabolism in the placenta were the key changed pathways involved in the above changes. Our study indicates that exposure to BP-3 can induce placental thrombosis and fetal loss via the disruption of maternal and fetal metabolism in mice, providing novel insights into the influence of BP-3 toxicity on the female reproductive system.

Impact of fluid overload on blood pressure variability in patients on peritoneal dialysis.

Fluid overload is a common complication in patients who are on continuous ambulatory peritoneal dialysis (CAPD). Blood pressure is the traditional indicator of fluid status in these patients. However, it has poor sensitivity. Blood pressure variability (BPV) can detect fluctuations in blood pressure sooner and more accurately and be useful for the assessment of fluid volume in hemodialysis patient. However, there are limited relevant studies involving patients on CAPD. This retrospective study included 175 patients on CAPD who underwent regular assessment of the peritoneal dialysis adequacy at 2-3-month intervals at our center from January 2018 to December 2020. The overhydration (OH) value was measured using a body composition monitor. Blood pressure measurements obtained in each visit over one-year follow-up were used to determine each patient's BPV under peritoneal dialysis. The patients were divided into the normal volume (OH ≤2 L), mild volume overload (OH 2-4 L), and severe volume overload groups (OH ≥4 L). There was no significant between-group difference in the mean blood pressure (p > 0.05). However, the systolic and diastolic BPV values were significantly higher in the severe volume overload group than in the other groups (p < 0.05). Further correlation and regression analysis showed volume overload severity and BPV existed positive association, and BPV was also significantly associated with PD volume related indexes, including diabetes mellitus, blood parathyroid hormone levels, Kt/V and subjective global assessment scores in the volume overloaded group (p < 0.05). All these results suggested BPV may be a useful indicator for fluid status in PD patients.

Neuregulin-1 alleviate oxidative stress and mitigate inflammation by suppressing NOX4 and NLRP3/caspase-1 in myocardial ischaemia-reperfusion injury.

Neuregulin-1 (NRG-1) is reported to be cardioprotective through the extracellular-regulated protein kinase (ERK) 1/2 pathway in myocardial ischaemia-reperfusion injury (MIRI). NOX4-induced ROS activated NLRP3 inflammasome and exacerbates MIRI. This study aims to investigate whether NRG-1 can suppress NOX4 by ERK1/2 and consequently inhibit the NLRP3/caspase-1 signal in MIRI. The myocardial infarct size (IS) was measured by TTC-Evans blue staining. Immunohistochemical staining, real-time quantitative PCR (RT-qPCR) and Western blotting were used for detection of the factors, such as NOX4, ERK1/2, NLRP3, caspase-1 and IL-1ß .The IS in the NRG-1 (3 µg/kg, intravenous) group was lower than that in the IR group. Immunohistochemical analysis revealed NRG-1 decreased 4HNE and NOX4. The RT-qPCR and Western blot analyses revealed that NRG-1 mitigated the IR-induced up-regulation of NOX4 and ROS production. Compared with the IR group, the NRG-1 group exhibited a higher level of P-ERK1/2 and a lower level of NLRP3. In the Langendorff model, PD98059 inhibited ERK1/2 and up-regulated the expression of NOX4, NLRP3, caspase-1 and IL-1ß, which exacerbated oxidative stress and inflammation. In conclusion, NRG-1 can reduce ROS production by inhibiting NOX4 through ERK1/2 and inhibit the NLRP3/caspase-1 pathway to attenuate myocardial oxidative damage and inflammation in MIRI.

Blood-brain barrier integrity in the pathogenesis of Alzheimer's disease.

The blood-brain barrier (BBB) tightly controls the molecular exchange between the brain parenchyma and blood. Accumulated evidence from transgenic animal Alzheimer's disease (AD) models and human AD patients have demonstrated that BBB dysfunction is a major player in AD pathology. In this review, we discuss the role of the BBB in maintaining brain integrity and how this is mediated by crosstalk between BBB-associated cells within the neurovascular unit (NVU). We then discuss the role of the NVU, in particular its endothelial cell, pericyte, and glial cell constituents, in AD pathogenesis. The effect of substances released by the neuroendocrine system in modulating BBB function and AD pathogenesis is also discussed. We perform a systematic review of currently available AD treatments specifically targeting pericytes and BBB glial cells. In summary, this review provides a comprehensive overview of BBB dysfunction in AD and a new perspective on the development of therapeutics for AD.

Post-COVID-19 Epidemic: Allostatic Load among Medical and Nonmedical Workers in China.

BACKGROUND: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. OBJECTIVE: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. METHODS: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. RESULTS: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18-1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17-1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14-1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18-1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34-1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78-0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80-0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72-0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87-0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22-0.41; p < 0.01) were negatively associated. CONCLUSIONS: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.

Pseudogene HSPB1P1 contributes to renal cell carcinoma proliferation and metastasis by targeting miR-296-5p to regulate HMGA1 expression.

With the aid of next-generation sequencing technology, pseudogenes have been widely recognized as functional regulators in the development and progression of certain diseases, especially cancer. Our present study aimed to investigate the functions and molecular mechanisms of HSPB1-associated protein 1 pseudogene 1 (HSPB1P1) in renal cell carcinoma (RCC). HSPB1P1 expression at the mRNA levels was determined by quantitative real-time polymerase chain reaction, and its clinical significance was assessed. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were detected by transwell assays. The location of HSPB1P1 in RCC cells was detected by subcellular distribution analysis. The direct relationship between HSPB1P1 and miR-296-5p/HMGA1 axis was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Our results identify the elevated expression of HSPB1P1 in RCC tissues and cell lines, which predicted advanced progression and poor prognosis in patients with RCC. Knockdown of HSPB1P1 suppressed cell proliferation, migration, and invasion, and reversed epithelial-mesenchymal transition process in RCC. HSPB1P1 was mostly enriched in the cytoplasm and functioned as a miRNA sponge for miR-296-5p and then regulated high-mobility group A1 expression. In conclusion, our study indicated that HSPB1P1 contributed to RCC progression by targeting the miR-296-5p/HMGA1 axis, and should be considered as a promising biomarker and therapeutic target for clinical applications.

Obstetric and Gynecologic Outcomes after the Transvaginal Repair of Cesarean Scar Defect in a Series of 183 Women.

STUDY OBJECTIVE: To analyze retrospectively the effect of hysteroscopy combined with transvaginal repair on the cesarean section diverticulum (CSD) and explore the clinical significance of this procedure. DESIGN: Retrospective study. SETTING: University-affiliated hospital and a gynecology hospital. PATIENTS: A total of 183 patients with scar diverticulum after cesarean section were recruited from the Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan and Shenzhen In Vitro Fertilization Gynecological Hospital. INTERVENTIONS: In this study, we reported a surgical method for repairing uterine scar through uterine therapy and explored its clinical efficacy and pregnancy outcome. MEASUREMENTS AND MAIN RESULTS: The time of operation, volume of bleeding, and duration of hospitalization were recorded. The size of the scar diverticulum and the remaining myometrium were examined by B-mode ultrasonography before and after the operation. The length of the menstrual cycle and pelvic pain were recorded during follow-up to check the recovery of patients after surgery. The pregnancy of patients with pregnancy needs was recorded to check the pregnancy outcome. All 183 patients successfully completed the repair of the transvaginal uterus scar diverticulum with the help of a hysteroscopy examination. The mean (± standard deviation) operation time was 58.61 ± 18.56 minutes. The mean blood loss was 36.97 ± 22.32 mL. The mean hospital stay was 6.08 ± 1.89 days. In 57.14% of patients, the CSD completely disappeared, whereas the volume of CSD shrank by at least 50% in 88.95% of patients. The mean menstrual period of patients after surgery was 7.72 ± 2.68 days, which was significantly shorter than that recorded preoperatively (13.45 ± 3.69 days) (t = 19.62, p = .00). The pelvic pain disappeared in 81.08% of the patients. The mean postoperative thickness of the remaining muscular layer was 5.30 ± 1.27-mm, which was significantly higher than the preoperative value of 2.25 ± 0.92-mm (t = 28.21, p = .00). The mean postoperative thickness of the remaining muscular layer of patients with improved menstrual cycle was 5.40 ± 1.27-mm, which was significantly higher than the thickness of 4.88 ± 1.11-mm in patients without improved menstrual cycle (t = 2.31, p = .025). A total of 124 patients attempted to become pregnant, 83 of whom were successful. The pregnancy rate was as high as 66.95%, which included 2 scar pregnancies, 4 ectopic pregnancies, and 87 intrauterine pregnancies. No uterine rupture occurred. CONCLUSION: The transvaginal repair of the uterine diverticulum improved the symptoms and probability of a successful pregnancy effectively. This process is a surgical procedure to increase the thickness of the residual uterine muscle wall effectively.

Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) rates have continued to rise during the last few decades, yet the underlying mechanisms remain poorly understood. An emerging area of interest is the mediation of gene expression by DNA methylation during early pregnancy. Here, genome-wide DNA methylation from placental villi was profiled in both RPL patients and controls. Subsequently, differentially expressed genes were analysed for changes in gene expression. Many significant differentially methylated regions (DMRs) were identified near genes dysregulated in RPL including PRDM1. Differentially expressed genes were enriched in immune response pathways indicating that abnormal immune regulation contributes to RPL. Integrated analysis of DNA methylome and transcriptome demonstrated that the expression level of PRDM1 is fine-tuned by DNA methylation. Specifically, hypomethylation near the transcription start site of PRDM1 can recruit other transcription factors, like FOXA1 and GATA2, leading to up-regulation of gene expression and resulting in changes to trophoblast cell apoptosis and migration. These phenotypic differences may be involved in RPL. Overall, our study provides new insights into PRDM1-dependent regulatory effects during RPL and suggests both a mechanistic link between changes in PRDM1 expression, as well as a role for PRDM1 methylation as a potential biomarker for RPL diagnosis.

Human chorionic gonadotropin improves endometrial receptivity by increasing the expression of homeobox A10.

Homeobox A10 (HOXA10) is a characterized marker of endometrial receptivity. The mechanism by which hCG intrauterine infusion promotes embryo implantation is still unclear. This study seeks to investigate whether hCG improves endometrial receptivity by increasing expression of HOXA10. HOXA10 expression with human chorionic gonadotropin stimulation was analyzed in vitro and in vivo. Our results demonstrate that HOXA10 was decreased in the endometria of recurrent implantation failure patients compared to that in the healthy control fertile group, also we observed that hCG intrauterine infusion increased endometrial HOXA10 expression. HOXA10, blastocyst-like spheroid expansion area was increased, whereas DNA (cytosine-5-)-methyltransferase 1 was decreased when human endometrial stromal cells (hESCs) were treated with 0.2 IU/ml of hCG for 48 h. HOXA10 promoter methylation was also reduced after hCG treatment. Collagen XV (ColXV) can repress the expression of DNA (cytosine-5-)-methyltransferase 1, and hCG treatment increased the expression of ColXV. However, when the hESCs were treated with LH/hCG receptor small interfering RNA to knock down LH/hCG receptor, hCG treatment failed to repress DNA (cytosine-5-)-methyltransferase 1 expression or to increase ColXV expression. Our findings suggest that hCG may promote embryo implantation by increasing the expression of HOXA10.

Resistance training effect on serum insulin-like growth factor 1 in the serum: a meta-analysis.

BACKGROUND: The resistance exercise has drawn considerable attention to the level of insulin-like growth factor 1 in the serum. However, the relationship between resistance exercise and the level of insulin-like growth factor 1 in the serum is conflicting. This meta-analysis was performed to evaluate this relationship. METHODS: A systematic literature search up to May 2020 was performed and 22 studies were detected with 680 subjects. They reported relationships between resistance exercise and the level of insulin-like growth factor 1 in the serum. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated comparing the resistance exercise and the level of insulin-like growth factor 1 in the serum using the continuous method with a random or fixed-effect model. RESULTS: Significantly higher insulin-like growth factor 1 was observed in subjects performing resistance training for less than 16 weeks (OR, 4.03; 95% CI, 2.49-5.57, p<.001); subjects performing resistance training for more than 16 weeks (OR, 11.55; 95% CI, 6.58-16.52, p<.001); subjects older than 60 years (OR, 11.88; 95% CI, 9.84-13.93, p<.001); females (OR, 3.87; 95% CI, 2.26-5.49, p<.001) and males (OR, 16.82; 95% CI, 7.29-26.35, p<.001). However, significantly lower insulin-like growth factor 1 was observed in subjects younger than 60 years (OR, -4.80; 95% CI, -7.74 to -1.86, p=.001). CONCLUSIONS: However, the resistance exercise significantly increases insulin-like growth factor 1 in subjects older than 60 years, both males and females, and subjects performing resistance exercise for all any period. Surprisingly, resistance exercise significantly decreases insulin-like growth factor 1 in subjects younger than 60 years. This relationship forces us to recommend the resistance exercise to improve insulin-like growth factor 1 in serum.

Adipose tissue transplantation ameliorates lipodystrophy-associated metabolic disorders in seipin-deficient mice.

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue and can lead to hepatic steatosis, insulin resistance (IR), and dyslipidemia in humans. Adipose tissue secretes many adipokines that are central to the regulation of metabolism. In this study, we investigated whether transplantation of normal adipose tissue could ameliorate severe hepatic steatosis, IR, and dyslipidemia in lipoatrophic seipin knockout (SKO) mice. Normal adipose tissue from wild-type mice was transplanted into 6-wk-old SKO mice. At 4 mo after adipose tissue transplantation (AT), the transplanted fat survived with detectable blood vessels, and the reduced levels of plasma leptin, a major adipokine, were dramatically increased. Severe hepatic steatosis, IR, and dyslipidemia in SKO mice were ameliorated after AT. In addition, abnormal hepatic lipogenesis and ß-oxidation gene expression in SKO mice were improved after AT. Our results suggest that AT may be an effective treatment to improve lipodystrophy-associated metabolic disorders.