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We investigated the influence of DNA fragmentation index (DFI) on in vitro fertilization (IVF), embryo transfer (ET), and intracytoplasmic sperm injection (ICSI). We analyzed the semen parameters of 61 cycles in infertile couples undergoing IVF-ET and ICSI and determined DFI by sperm chromatin dispersion testing. Based on DFI, the patients were differentiated into a control group (DFI < 25%, n = 35) and a test group (DFI ≥ 25%, n = 26). Flow cytometry and immunofluorescence were used to investigate the extent of sperm reactive oxygen species (ROS) and apoptosis. We also investigated the effect of DFI on pregnancy outcomes of IVF-ET/ICSI. DFI was negatively related to sperm motility and positively correlated with ROS and apoptosis (P < 0.05). Abnormally elevated DFI reduced the rate of transplantable, high-quality embryos, implantation, clinical pregnancy, delivery, and live birth after IVF-ET, and increased the chance of early abortion per transfer cycle (P < 0.05). However, there was no significant correlation between DFI and fertilization rate, cleavage rate, transplantable rate, high-quality embryo rate, implantation rate, clinical pregnancy rate, early abortion rate, delivery rate and live birth rate when assisted by ICSI (P > 0.05). Sperm DNA integrity is crucial for fertilization and the development of healthy offspring. ROS may increase the level of DFI by inducing apoptosis in sperm.

Background: Premature ovarian insufficiency (POI) is a refractory disease that severely affects female fertility. The PERK/eIF-2α/ATF4/CHOP pathway is one of the classical pathways involved in the unfolded protein response to endoplasmic reticulum stress by regulating protein synthesis and promoting apoptosis. This study aimed to investigate the functional role and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in the POI animal model through the PERK/eIF-2α/ATF4/CHOP pathway. Methods and results: Forty-five sexually mature female C57 mice were divided into a blank control group, POI model group, and hUCMSCs intervention group. To establish the POI model, mice received intraperitoneal injections of cyclophosphamide (CTX) (70 mg/kg) daily for 14 consecutive days, while the control group received saline only. In the hUCMSC intervention group, mice were given hUCMSCs on days 14 and 28, based on CTX modeling in the POI model group. The hUCMSCs were isolated, labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) fluorescent dye, and tail vein-injected, and the distribution of the DiR signal was monitored in the mice using a fluorescence imaging detection method. The ovarian tissues were hematoxylin and eosin stained to observe the ovarian structure, and the number of primordial follicles were counted. An enzyme-linked immunosorbent assay was used to detect the serum levels of estradiol, anti-mullerian hormone, and follicle-stimulating hormone. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to detect the apoptosis of granulosa cells (GCs). The reactive oxygen species (ROS) content of ovarian tissue was detected by flow cytometry assay. The RNA expression of PERK, eIF-2α, ATF4, and CHOP was determined by quantitative real-time polymerase chain reaction, and protein levels of the targets were determined by western blot and immunohistochemistry. We identified hUCMSCs using surface antigenic markers (CD90, CD44, CD105, and CD73), and osteoblasts and chondroplast differentiation assays. Our studies demonstrated that hUCMSC intervention significantly restored ovarian function by improving the irregular estrous cycle, increasing the number of follicles, decreasing ROS, and inhibiting GC apoptosis in POI mice. Moreover, hUCMSCs suppressed CTX-induced PERK/eIF-2a/ATF4/CHOP pathway activation. Conclusions: HUCMSCs can migrate to the damaged ovaries of POI mice, and improve the ovarian function of POI mice by inhibiting oxidative stress, down-regulating the expression of the PERK/eIF-2α/ATF4/CHOP pathway, and reducing the apoptosis of GCs. [ABSTRACT FROM AUTHOR]

Introduction: This study was designed to investigate whether renal α‐klotho levels are associated with renal pathology. This is the first report on patients with chronic kidney disease (CKD). Methods: We conducted a retrospective observational study. A total of 65 CKD patients were enrolled. Serum and renal biopsy samples were collected. Estimated glomerular filtration rate (eGFR) was examined by biochemical test. And α‐klotho expressions were assessed by RT‐PCR and immunohistochemistry. In addition, detailed microscopic findings were reviewed. Results: Renal α‐klotho levels are associated positively with eGFR, and negatively with renal pathology, including interstitial fibrosis, inflammatory cell infiltration, and tubular atrophy. Conclusions: The renal α‐klotho is related to renal pathology. [ABSTRACT FROM AUTHOR]

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30–90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13–3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81–4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5–1.7) and 8.8 months (95% CI: 8.5–9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

Objective To explore the role of annexin A1 (ANXA1) in resveratrol regulation of M2 type polarization of rat microglial cell line with oxygen glucose deprivation/reoxygenation (OGD/R) model. Methods Lentivirus LV-shAnxA1 was used to silence the expression of AnxA1 in N9 cells. LV-Scramble acted as a control lentivirus. Western blot and RT-qPCR were used to verify the efficiency of lentivirus infection. 3 d after lentivirus infection, the N9 cell OGD/R model was constructed. 3 days after reoxygenation, the cells were treated with resveratrol for 24 hours. The groups were as follows: OGD/R(-) group, OGD/R(+) group, OGD/R(+)+Res group, OGD/R(+)+Res+LV-Scramble group, OGD/R(+)+Res+LV-shAnxA1. RT-qPCR and Western blot were used to detect the mRNA and/or protein content of ANXA1, CD11b, tumor necrosis factor (TNF-α), Interleukin-1β(IL-1β), arginase-1 (Arg-1) and Interleukin-10 (IL-10). Immunofluorescence was applied to observe the distribution of ANXA1 in cells. Results The level of ANXA1 mRNA and protein in OGD/R(+)+Res group was significantly higher than that in OGD/R(+) group. The ANXA1 protein in the OGD/R(+) group was mainly distributed in the nucleus,while the ANXA1 protein in the OGD/R(+)+Res group was mainly distributed in cytoplasm. After inhibiting the expression of ANXA1, the OGD/R(+)+Res+LV-shAnxA1 group ANXA1 was mainly located in the nucleus. Compared with the OGD/R(+)+Res group, the CD11b protein content in the OGD/R(+)+Res+LV-shAnxA1 group was significantly increased (P＜0.01), and the TNF-α and IL-1β mRNA levels were significantly increased(P＜0.001), while Arg-1 and IL-10 mRNA levels were significantly reduced. Conclusions Resveratrol promotes the polarization of rat microglial cell line wih OGD/R model to M2 type via upregulation of ANXA1 expression.

The quality of traditional sMDT(single-centered multi-disciplinary treatment team) teaching model will be affected by the centerlocation, leve of heathcare service, performance habits, dominant disciplines, and superior technologies, which will directly affect the depth and breadth of students' knowledge learning. Based on the traditional sMDT teaching, the new multi-centered MDT (mMDT) teaching model establishes cooperative teaching relationships with multiple hospitals and disciplines, cocultivates undergraduate and graduate students, and regularly conducts mMDT teaching, which effectively avoids the defects of the traditional sMDT teaching model and meets the needs of students at different levels. Through the mMDT teaching mode, students can learn the advanced clinical reasoning and techniques in different disciplines or hospitals, have a deeper understanding of the concept of comprehensive diagnosis and treatment of tumors, and improve the comprehensive quality of clinical research.

In the context of digital transformation of manufacturing enterprises, the research method of double case comparison analysis is used to explore the implementation path of C2B digital intelligence customization of "new infrastructure". The research found that: C2B personalized digital intelligence customization implements digital intelligence supply chain construction strategy, through supply chain digital intelligence transformation, realizes front-end and back-end collaboration, can reduce production costs, improve demand collection and production efficiency, and the implementation path is "digital intelligence supply chain construction → digital intelligence capability improvement → digital intelligence value realization". The research results can not only provide reference for decision making of new infrastructure, but also provide guidance for the path selection of digital transformation of enterprises.