Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Objective:To synthesize 18F labeled PET imaging probe based on giredestrant (GDC-9545), an estrogen receptor α (ERα) degrader and antagonist, and evaluate its ERα-targeting properties. Methods:The precursor-GDC (PGDC), GDC and 18F-GDC were synthesized. The radiochemical yields, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-GDC were determined. Cellular uptake and blocking assays of 18F-GDC were performed using ERα high-expressing MCF-7 cells and ERα low-expressing MDA-MB-231 cells. MCF-7 and MDA-MB-231 tumor-bearing mice were constructed and microPET imaging was performed. The biodistribution of 18F-GDC in MCF-7 tumor-bearing mice was studied. Data were analyzed by using two-way repeated measures analysis of variance and Bonferroni correction method. Results:PGDC and GDC were successfully prepared with the purity more than 95%. 18F-GDC was successfully synthesized with the labeling yield of (11.25±3.18)%, radiochemical purity more than 98%, specific activity of (140.66±17.20)GBq/μmol and lipid water partition coefficient log P of 2.12±0.13. 18F-GDC was stable in PBS or mouse serum, with the radiochemical purity still more than 98% after 2 h of incubation. After incubation for 60 and 120min, the uptakes of 18F-GDC in MCF-7 cells were significantly higher than those in MDA-MB-231 cells ( F values: 113.78, 369.70, P values: 0.002, 0.001 (Bonferroni correction method)), and could be blocked by GDC. 18F-GDC had a high uptake in MCF-7 tumors and could be blocked by GDC. Tumor uptake at 60 min post-injection was (7.23±0.74) percentage activity of injection dose per gram of tissue (%ID/g) and the tumor/muscle uptake ratio was 2.83±0.29 in MCF-7 tumors, while 18F-GDC had a lower uptake in MDA-MB-231 tumors, with (2.01±0.46)%ID/g at 60min post-injection, and a tumor/muscle uptake ratio of 0.96±0.22 ( F values: 77.28, 55.44, P values: 0.002, 0.006 (Bonferroni correction method)). 18F-GDC was mainly distributed in MCF-7 tumors and organs including heart, liver, spleen, kidney, stomach and intestines. Conclusions:18F-GDC is successfully synthesized, with high radiochemical purity and stability, and can concentrate in the ERα-overexpressing cancer cells and lesion area of xenograft tumor mouse. It presents good image contrast in PET imaging, indicating excellent diagnostic performance.

Objective:To design and synthesize a 18F-labeled small molecule PET imaging probe targeting carbonic anhydrase Ⅸ (CAⅨ), named as 18F-single-acetazolamide (SAZ), and to evaluate its biological properties preliminarily. Methods:Acetazolamide was used as raw material to synthesize the precursor SAZ, and the target probe 18F-SAZ was obtained through nucleophilic substitution and other reactions. The radiochemical yield, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-SAZ were determined. Cancer cell lines OS-RC-2 (CAⅨ-positive) and HCT116 (CAⅨ-negative) were used for cell uptake experiments, and corresponding tumor-bearing mice were constructed for microPET imaging. Biodistribution of the probe in OS-RC-2 tumor-bearing mice was analyzed. The difference among groups was analyzed by repeated measures analysis of variance and Bonferroni method. Results:The probe 18F-SAZ was successfully prepared with the labelling yield of (5.60±0.51)%, specific activity of (7.90±0.62)MBq/nmol, radiochemical purity more than 99%, and the lipid water partition coefficient log P of -0.38±0.01. After incubation with PBS or mouse serum for 4 h, the radiochemical purity was still more than 99%. The uptake of 18F-SAZ in OS-RC-2 cells reached (1.47±0.24) percentage of the added radioactivity dose (%AD) at 30min, which was significantly higher than the uptake in the blocked group and that in HCT116 cells ((0.60±0.07)%AD, (0.50±0.05)%AD; F=24.31, P values: 0.012, 0.013 (Bonferroni correction method)). The results of microPET imaging showed that the uptake of 18F-SAZ in OS-RC-2 tumors reached the maximum at 30min ((2.92±0.07) percentage activity of injection dose per gram of tissue (%ID/g)), while the maximum uptakes in the blocked group and HCT116 tumors were only (1.36±0.02) and (1.12±0.07)%ID/g, respectively. 18F-SAZ was mainly distributed in tumors and organs including kidney, intestine, liver, stomach in OS-RC-2 tumor-bearing mice. Conclusions:The probe 18F-SAZ is successfully synthesized. It has high radiochemical purity and good stability in vitro, and can specifically target tumor cells with high expression of CAⅨ. It is expected to be a new CAⅨ-targeting PET imaging probe.

Under the background of the Healthy China Strategy, public hospitals urgently need to break through the limitations of the traditional medical mode, build a precise and continuous medical service system to meet the growing personalized health needs of the people. In 2022, a tertiary public hospital launched a multidisciplinary whole course management service practice. By integrating multidisciplinary medical and health resources, clarifying service targets and contents, forming a whole course management service team, constructing a supporting information platform, linking full process services, creating standardized service processes, and providing patients with comprehensive, full process, professional, and accurate full cycle intervention management and care. The hospital covered diseases in stages, ensuring continuous medical for patients after leaving the hospital, improving their medical experience, and supporting the high-quality development of the hospital. As of June 2024, the hospital′s multidisciplinary whole course management services had covered 25 departments and 41 disease, and 43 management teams have been established. A total of 7 453 patients signed up for the whole course service. This practice achieved good results, could provide references for the implementation of whole course management services led by public hospitals.

Objective:In order to clarify the ABO phenotype and genotype,and explore the molecular biological mechanism,serological detection,genotyping and gene sequencing were performed on an upper gastrointestinal hemorrhage patient with inconsistent forward and reverse ABO blood typing.Methods:ABO forward and reverse blood typing,H antigen identification,capillary centrifugation test and salivary substance detection were performed by classical serological method,moreover,polymerase chain reaction-sequence specific primer(PCR-SSP)was used for ABO genotyping,ABO gene 1-7 exons were sequenced by Sanger analysis in order to identify mutation.Results:Mixed field agglutination with anti-A,anti-AB and no agglutination with anti-A1 were appeared in the forward typing tests,agglutination with B cells but no agglutination with A1 cells and O cells were appeared in the reverse typing tests.3+agglutination strength was showed with anti-H.In capillary centrifugation experiment,erythrocyte after isolation in proximal part and distal end had same strength of agglutination with anti-A.Substances A and H were detected in saliva.The patient was assigned an A3 phenotype according to serological characteristics.Sequencing results of ABO gene 1-7 exons showed c.261delG,c.467C＞T,c.865A＞G,in which,865A＞G was the first discovered mutation,and this new mutation had been submitted to GenBank with accession number PP187306.Conclusion:A novel site mutation c.865A＞G is reported in this study,and this new mutation can result in a replacement of Met with Val at residue 289(p.Met289Val)and lead to an A3 phenotype.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Objective To investigate the feasibility and safety of transoral transgastric natural orifice transluminal endoscopic surgery(TG-NOTES)cholecystectomy in miniature pigs.Methods A total of 11 miniature pigs were selected as the experimental subjects and underwent TG-NOTES cholecystectomy.These pigs were divided into the Group A and Group B according to the surgical procedures.Among them,7 miniature pigs in the Group A underwent endoscopic cholecystectomy without dissecting the gallbladder triangle,while 4 miniature pigs in the Group B underwent endoscopic cholecystectomy after dissecting the gallbladder triangle.The success rate of surgery,the time of each stage of surgery,the incidence of complications,the success rate of cholecystectomy and the survival rate of miniature pigs in the two groups were counted.One miniature pig in the Group A and 4 miniature pigs in the Group B were selected for survival experiments.After surviving for 1 week,they were killed and dissected to observe the healing of incision and incidence of complications.Results The surgical survival rate of experimental animals was 100%,and the success rate of cholecystectomy was 100%.There was no significant difference in the surgical time,time of cut the stomach into the abdomen,time of gallbladder exploration or time of gallbladder removal of miniature pigs between the two groups(P>0.05).The time of ligating gallbladder artery of miniature pigs in the Group B was longer than that in the Group A,and the time of isdating gallbladder was shorter than that in the Group A,with statistically significant differences(P<0.05).There was no significant difference in the average number of complications of miniature pigs between the two groups(P>0.05).The dissection of animals after survival experiments revealed that the incisions healed well without serious complications.Conclusion This study successfully establishes the surgical model of TG-NOTES cholecystectomy,and confirms the safety and feasibility of TG-NOTES cholecystectomy.