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.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:Using single cell sequencing to analyze the characteristics of the immune repertoire of SARS-CoV-2 pa-tients at different infection stages,and to explore the possible pathogenesis.Methods:Obtaining data in the NCBI database,and healthy control,progression and convalescence groups were set up.Analysis of single cell sequencing data by RStudio,Origin,Hipliot and Excel software.Results:TCR plays an important role in antigen recognition and virus clearance.Characteristics of the three immune repertoires are very different.The number of clones exceeded 26.92%.The length distribution of α chain CDR3 was con-centrated on 14 amino acids,while β-chain was concentrated on 15 amino acids.The frequency of gene fragments in V and J regions were different,and the frequency of TRAV13-1,TRAJ20,TRBV20-1 and TRBJ2-1 were statistically significant(P<0.05).Further V-J gene combination analysis showed that there were significant differences in the frequency of single chain V-J between the control group and the progression group,the control group and the rehabilitation group(P<0.05).The highest frequency of αβ double chain V-J in the control group was TRAV19-J34-TRBV4-1-J2-1,the highest frequency of αβ double-stranded V-J in the progression group was TRAV12-1-J30-TRBV19-1-J2-1,and the highest frequency of αβ double chain V-J in the convalescence group was TRAV12-2-J52-TRBV7-9-J1-5.Conclusion:This study analyzes the global characteristics of T cells in the immune repertoire,which is helpful to understand the pathogenesis of SARS-CoV-2 patients,timely and effective treatment of patients in the early stages of infection.

The bionic optic nerve can mimic human visual physiology and is a future treatment for visual disorders. Photosynaptic devices could respond to light stimuli and mimic normal optic nerve function. By modifying (Poly(3,4-ethylenedioxythio-phene):poly (styrenesulfonate)) active layers with all-inorganic perovskite quantum dots, with an aqueous solution as the dielectric layer in this paper, we developed a photosynaptic device based on an organic electrochemical transistor (OECT). The optical switching response time of OECT was 3.7 s. To improve the optical response of the device, a 365 nm, 300 mW·cm ^-2 UV light source was used. Basic synaptic behaviors such as postsynaptic currents (0.225 mA) at a light pulse duration of 4 s and double pulse facilitation at a light pulse duration of 1 s and pulse interval of 1 s were simulated. By changing the way light stimulates, for example, by adjusting the intensity of the light pulses from 180 to 540 mW·cm ^-2, the duration from 1 to 20 s, and the number of light pulses from 1 to 20, the postsynaptic currents were increased by 0.350 mA, 0.420 mA, and 0.466 mA, respectively. As such, we realized the effective shift from short-term synaptic plasticity (100 s recovery of initial value) to long-term synaptic plasticity (84.3% of 250 s decay maximum). This optical synapse has a high potential for simulating the human optic nerve.
Humans ; Quantum Dots ; Bionics ; Oxides ; Optic Nerve

Objective:To investigate the application of three-dimensional image reconstruction combined with problem-based learning (PBL) in the teaching of physicians receiving continuing education in thoracic surgery.Methods:A total of 68 physicians who received continuing education in Department of Thoracic Surgery in our hospital were selected as research subjects, and they were divided into control group and observation group using a random number table, with 34 physicians in each group. The physicians in the control group received traditional teaching, while those in the observation group received three-dimensional image reconstruction combined with PBL teaching. A questionnaire survey, theoretical assessment, and assessment of practical skills were performed to evaluate the effect of teaching. SPSS 22.0 was used to perform the t-test. Results:Compared with the control group, the observation group had significantly higher degrees of satisfaction with each item of the questionnaire survey ( P<0.05). Compared with the control group, the observation group had significantly higher scores of theoretical assessment [(94.07±6.03) vs. (86.34±5.46), P<0.001] and the assessment of practical skills [(95.20±5.48) vs. (84.71±6.14), P<0.001]. Conclusion:The application of three-dimensional image reconstruction combined with PBL teaching can help to improve the comprehensive ability of physicians receiving continuing education.

Background: and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

OBJECTIVE： To observe the efficacy and safety of apatinib combined with systemic chemotherapy for hepatic metastasis of gastroenteropancreatic neuroendocrine neoplasms （GEP-NEN）. METHODS： Totally 60 patients with GEP-NEN in Hubei Provincial Tumor Hospital from Jan. 2016 to Jan. 2018 were randomly divided into systemic chemotherapy group， apatinib group and combination group， with 20 patients in each group. Systemic chemotherapy group was given Etoposide injection 80 mg/m2，once a day d1-5， intravenously+Cisplatin for injection 20 mg/m2，once a day d1-5，intravenously， every 3 weeks for a cycle. Apatinib group was given Apatinib mesylate tablets 0.5 g， once a day. Combination group received treatment as systemic chemotherapy group+apatinib group. All three groups were treated continuously for 3 months. The clinical efficacies of 3 groups were observed. The serum levels of tumor markers （CEA， NSE， CgA and CA19-9） before and after treatment， survival situation after treatment and the occurrence of ADR during treatment were also observed. RESULTS： The objective remission rate， disease control rate， median overall survival and survival rate of combination group were significantly higher or longer than those of systemic chemotherapy group and apatinib group. Median progression-free survival and the incidence of ADR were significantly shorter or lower than systemic chemotherapy group and apatinib group （P＜0.05）. After treatment， the levels of CEA， NSE， CgA and CA19-9 in 3 groups were significantly lower than before treatment， and combination group was significantly lower than systemic chemotherapy group and apatinib group （P＜0.05）. There was no statistical significance in above indexes between systemic chemotherapy group and apatinib group （P＞0.05）. CONCLUSIONS： Apatinib combined with systemic chemotherapy for liver metastasis of GEP-NEN is effective and safe， which can improve the level of serum tumor markers， prolong the survival time of patients and improve survival rate.

Objective To explore application of our self-designed U-shaped transdermal surgical navigator based on three-dimensional reverse design in cannulated screwing for femoral neck fracture Methods A retrospective study was done of 5 patients with femoral neck fracture who had been treated from August 2016 to March 2017.They were 3 men and 2 women,aged from 33 to 60 years (average,46.5 years).Thin layer CT scanning was conducted on the patients' affected hip (at the left side in 2 cases and at the right side in 3).Based on their CT data,3D design software and 3D printing technique were used to manufacture the U-shaped transdermal surgical navigator and a real-sized model of the fracture.Operations were simulated using the U-shaped transdermal surgical navigator on the fracture model to determine the angle,depth and location of the screwing.Fixation of the fracture with cannulated screws was conducted after confirmation of satisfactory surgical parameters.The postoperative X-ray films of the patients were reviewed.Evaluations were conducted of the screw position,operating time,volume of operative bleeding,and number of intraoperative X-ray shots.Results The screw positions in the 5 patients were consistent with their preoperative design.Four patients had only one shot of fluoroscopy and one patient 3 shots.Their operating time ranged from 15 to 30 minutes,averaging 22.5 minutes;their bleeding ranged from 5 to 10 mL,averaging 7.5 mL.The 5 patients were followed up for an average of 4.5 months (from 3 to 6 months).By the Harris scoring at their final follow-ups,one was excellent,3 good and one fair.No complications like pain,functional impairment of the joint,or collapse or necrosis of the femoral head occurred during the follow-up.Conclusions Our self-designed U-shaped transdermal surgical navigator based on three-dimensional reverse design can significandy improve the accuracy and safety of the cannulated screwing for femoral neck fractures.The operation is minimally invasive,reducing operating time and intraoperative blood loss.

Objective To conduct an epidemiological investigation on a case of familial arsenic poisoning in Yunnan Province,to find arsenic poisoning source and create a archive of typical cases,in order to raise awareness of endemic arsenicosis and provide scientific materials for prevention and treatment of the disease.Methods In Xiaxiaoying Village of Yunnan Province,all members of a family with arsenic poisoning patients were investigated in 2013,their health examination and epidemiological survey of arsenic poisoning were carried out,and arsenic poisoning family profiles and personal files were established.Drinking water,hair and urine samples were collected for arsenic content determination,blood samples were collected for biochemical detection,excessively keratose skin was collected for pathological biopsy.Results A total of 33 family members were investigated.Among them 15 were exposed to arsenic and 18 were not exposed to arsenic.Fifteen people exposed to arsenic were found to be have skin lesions,and two eldest males died of skin cancer and cerebral hemorrhage in 1994 and 2009,respectively.The survey found out that 15 patients born in 1935-1983 had been drinking arsenic pesticides polluted well water for 5 to 16 years from 1973 to 1989.As of 2013,the arsenic exposure had been stopped for 24 years,the content of arsenic in the polluted wells was 0.624 mg/L,which was 62.4 times the recommended maximum limit (0.01 mg/L) of the World Health Organization.The median of hair and urinary arsenic in arsenic exposed population and non-arsenic exposed population was 4.2,3.7 mg/kg and 60.9,41.0 μg/L,respectively.There was no statistically significant difference in hair arsenic (Z =-1.905,P ＞ 0.05),but the difference of urinary arsenic was statistically significant (Z =-3.002,P ＜ 0.05).The median of aspartate aminotransferase (AST),gammaglutamyltransferase (γ-GT) and 24 hours urinary ereatinine (Cr) in arsenic exposed population and non-arsenic exposed population was 37.5,31.0 U/L,25.5,12.0 U/L,13 834.0,and 6 843.0 μmol/L,respectively.The differences between the two groups were statistically significant (Z =-2.776,-2.311,-2.502,P ＜ 0.05).Twelve cases of arsenic poisoned patients who were conducted health examination and epidemiological investigation showed typical triad of skin,among them 2 cases were moderate and 10 cases were severe.Pathological biopsy results showed 8 cases had basal cell carcinoma or squamous cell carcinoma.Conclusions Drinking arsenical pesticide contaminated water can induce chronic arsenic poisoning,even after the cessation of arsenic exposure.We should pay close attention to its long-term serious harmful effect.