Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

Infertility is a common reproductive disorder affecting millions of couples worldwide. It is estimated that male factors account for about 30%-50% of infertility cases, and some studies have found that the concentration of male sperm gradually decreases over time, a trend that suggests the importance of male fertility. Many factors contribute to the decline of male fertility, among which environmental factors have received widespread attention. After reaching adulthood, spermatogonial stem cells will continue to produce sperm, but these cells exist outside the blood testicular barrier, which makes them highly sensitive to environmental conditions such as air pollution, tobacco smoke, radiation, and heavy metals. It is reported that exposure to these adverse environmental factors not only causes oxidative stress and DNA damage to germ cells, but also leads to abnormal epigenetic modification of sperm DNA, thereby causing a series of diseases. This article reviewed the abnormal methylation changes in DNA associated with exposure to environmental pollutants during spermatogenesis and how these changes affect the quantity, quality, and function of spermatozoa.

Trauma is the main cause of death and disability. Patients with severe trauma have hemorrhagic shock, traumatic coagulopathy and other diseases, which increase the risk of death. Platelets are important in the hemostatic response, but their function is rapidly dysregulated in trauma patients, leading to traumatic coagulopathy, blood loss, and early death. In addition to their role in hemostasis, platelets act as coordinators of the initial immune response, which can lead to immunothrombosis, organ dysfunction, and increased late mortality. At present, the treatment of post traumatic platelet dysfunction is mainly based on early hemostasis, and late prevention and treatment of thrombosis and organ dysfunction. In this review, the characteristics, underlying mechanisms, diagnosis and treatment strategies of platelet dysfunction in different periods are summarized, to provide ideas for studying the mechanism of platelet dysfunction after trauma and the treatment strategy for trauma patients.
Humans ; Wounds and Injuries/therapy* ; Blood Platelets/metabolism* ; Blood Platelet Disorders/etiology* ; Animals ; Hemostasis

Humans ; Albumins ; Albuminuria/urine* ; Blood Pressure ; China/epidemiology* ; Creatinine ; Risk Factors ; Aged

Objective:To analyze the relevant factors affecting postnatal glucose metabolism in pregnant women with gestational diabetes and construct a nomogram prediction model.Methods:Using a retrospective study method, 210 cases of gestational diabetes patients admitted to Danyang People′s Hospital from March 2019 to November 2021 were selected as the study subjects, and they were divided into 125 cases of normal group and 85 cases of abnormal group according to the postnatal glucose metabolism. The predictive value was analyzed using the subject work characteristics (ROC) curve experiment; the risk factors affecting abnormal postpartum glucose metabolism in pregnant women with gestational diabetes mellitus were analyzed using Logistic regression experiment; and the clinical efficacy of the column-line diagram model was verified using internal data.Results:There was no statistically significant difference between the two groups when comparing the general information such as age ( P>0.05); compared with the normal group, the abnormal group had higher values of total cholesterol (TG), postprandial 2 h blood glucose (OGTT 2 h), glycosylated hemoglobin, and pre-pregnancy body mass index (BMI): (4.23 ± 1.35) mmol/L vs. (3.65 ± 1.50) mmol/L, (9.36 ± 1.25) mmol/L vs. (8.20 ± 1.51) mmol/L, (8.31 ± 2.96)% vs. (6.73 ± 2.23)%, (24.96 ± 4.21) kg/m 2 vs. (23.20 ± 3.25) kg/m 2, and those with a family history of diabetes mellitus were higher: 47.06%(40/85) vs. 20.80%(26/125), there were statistical differences ( P<0.05); the area under the curve (AUC) of TG, OGTT 2 h, glycated hemoglobin, and pre-pregnancy BMI were 0.605, 0.720, 0.670, and 0.616, with optimal cut off values of 4.65 mmol/L, 8.33 mmol/L, 8.06%, and 25.27 kg/m 2; TG (>4.65 mmol/L), OGTT 2 h (>8.33 mmol/L), glycated hemoglobin (>8.06%), and preconception BMI (>25.27 kg/m 2), and family history of diabetes mellitus (yes) were risk factors for abnormal glucose metabolism in pregnant women ( P<0.05); the C-index of the risk of postpartum glucose metabolism in pregnant women with gestational diabetes mellitus predicted by the column chart model was 0.750 (95% CI 0.672 - 0.864). The model predicted that the threshold of the risk of postnatal glucose metabolism in pregnant women with gestational diabetes mellitus was >0.07. Conclusions:TG (>4.65 mmol/L ), OGTT 2 h (>8.33 mmol/L ), glycated haemoglobin (>8.06%), pre-pregnancy BMI (>25.27 kg/m 2), and family history of diabetes (yes) are risk factors for abnormal glucose metabolism in pregnant women, and the model constructed based on the variables have good predictive power.

Objective The reliability and validity of the SGGC-Net-based motion capture system(SGGC-Net system)and SIMI system for parsing walking gait were compared using a three-dimensional(3D)motion capture system(Vicon)with marker points as a reference standard.Methods Thirty healthy college students were recruited,and their gait characteristics while walking on a treadmill were analyzed.Kinematic data were collected using the Vicon system,and video data were collected synchronously using four cameras to obtain the right shoulder,elbow,hip,knee,and ankle joint angles.Reliability was assessed using intraclass correlation coefficients(ICCs)with 95％confidence intervals and standard error of measurement(SEM).Validity was assessed using multiple correlation coefficients(MCCs)and root mean square errors(RMSEs).Results The ICCs of the maximum and minimum 3D coordinate angles of the upper and lower limb joints of the SGGC-Net system ranged from 0.798-0.990 with an SEM of 0.04°-0.95°,and the ICCs of the SIMI system ranged from 0.650-0.967,with an SEM of 0.31°-1.24°.The ICCs of the SGGC-Net system were higher than those of the SIMI system for all joint angles except for the minimum hip and maximum knee angles.Compared to the joint angle curves derived from the SIMI system,the MCCs of the curves derived from the SGGC-Net system ranged from 0.945-0.996,with RMSEs of 1.44°-4.65°,and the multiple correlation coefficients of the SIMI system ranged from 0.815-0.986,with RMSEs of 2.56°-9.99°.The MCCs of the SGGC-Net system were greater than those of the SIMI system at all angles except for the ankle joint.The RMSEs of the SGGC-Net system were smaller than those of the SIMI system at all angles except for the ankle joints.Conclusions The SGGC-Net system has better reliability and validity than the SIMI system in most of the variables,and it has better repeatability and accuracy in analyzing walking gait.It can be applied to motion capture environments without marker points,such as technical analysis of athletes'movements and clinical gait analysis of special populations.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.

Objective: To explore the activity of auranofin against ovarian cancer cells and its possible molecular mechanism． Methods : The dose-response survival curve and IC50 of auranofin on ovarian cancer cell lines ，SKOV3，Caov3 and SW626 cells and immortalized normal human embryonic kidney HEK-293T cells were determined by CCK-8 method．Cell cycle was determined by flow cytometry．The levels of total glutathione ( GSH) ，reduced GSH and glutathione disulfide ( GSSG) ，thioredoxin reductase (TrxR) and reactive oxygen species (ROS) in cells were determined by microplate reader，and the reduced GSH / GSSG ratio was calculated．Western blot was used to determine the expression of cyclin dependent kinases( CDK) 4，CDK6，Cyclin D1，P53，p-P53 and MDM2 in SKOV3 and Caov3 ovarian cancer cells. Results : Compared with HEK-293T cells，the dose-response survival curves and IC50 values of SKOV3，Caov3 and SW626 cells showed that ovarian cancer cells were more sensitive to auranofin (P＜0. 05) ．After SKOV3 and Caov3 cells were treated with the dose of respective IC50 concentrations of auranofin，compared with the untreated cells group，the Auranofin IC50 group cells' intracellular levels of GSH，the ratio of reduced GSH / GSSG and the activity of TrxR decreased (t = 25. 11 /31. 18，14. 72 /19. 92，43. 30 /10. 74， all P＜0. 05) ，and the levels of ROS increased (t = 23. 82 /27. 71，P＜0. 05) ; cells number at G0 / G1 phases increased，with cells number at S and G2 phases decreased (P＜0. 05) ; and the expression levels of cell cycle-related proteins CDK4，CDK6，Cyclin D1 and the P53-specific E3 ubiquitin ligase MDM2 were down-regulated (t = 7. 51 /15. 59，17. 32 /11. 26，20. 78 /20. 78，24. 25 /17. 32，all P＜0. 05) ，while the expression levels of P53 and p-P53 were up-regulated (t = 17. 32 /24. 25，12. 12 /10. 39，all P ＜0. 05) ． Conclusion Auranofin causes oxidative stress in ovarian cancer cells by inhibiting TrxR activity，and by partially degrading MDM2 to stabilize and acti- vate P53，so as to block the cancer cells in G0 / G1 phase，and exert anti-ovarian cancer activities.

The prevention and control of hospital infections(hereinafter referred to as infection control) is key to the implementation of " medical and prevention integration" in medical institutions. And the professional knowledge and skill level of infection control professionals is one of the critical factors directly affecting the infection control capacity of these institutions. Jiangsu Province has been exploring to establish a job training system for newly recruited full-time infection control staff since 2021 based on their core competency needs. In January 2022, the new training system was put into use. The province formulated a training outline for new full-time infection control personnel, established a provincial-level infection control trainers pool through training and competitive selection, and then selected the best ones for provincial infection control full-time personnel training bases. Then the province organized job training covering both theoretical learning and practical aspects, and examined their corresponding theoretical knowledge and practical operation. Theoretical learning was made via online courses; Practical training was made at designated tertiary hospitals, covering clinical practice in key departments, environmental hygiene monitoring, hospital infection case monitoring, and application of infection control information systems. Among 804 new full-time personnel trained in 2022, 567 passed the graduation examination at a pass rate of 70.52%. The job training system for new full-time infection control personnel built in Jiangsu Province proves useful for the management of job training for such personnel in other provinces.