Objective To observe the effects of acupoint catgut embedding therapy on body mass,lipid metabolism,serum leptin and mRNA and protein expressions of hypothalamic leptin receptor(LepR)-mediated Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway in rats with diet-induced obesity(DIO).Methods Forty male SD rats were randomly divided into 10 in normal group and 30 in modeling group.A high-fat diet was used to establish the DIO rat model.After successful modeling,the modeled rats were randomly divided into the model group,the acupoint catgut embedding group and the acupoint catgut embedding + AG490(JAK2/STAT3 pathway blocker)group,with 10 rats in each group.The acupoint catgut embedding group and the acupoint catgut embedding + AG490 group were embedded on day(s)1,8,15 and 22 after successful modeling,the acupoints were selected from the Zhongwan(RN12),Shuidao(ST28),Tianshu(ST25),Pishu(BL20),Weishu(BL21),Sanjiaoshu(BL22)with a total of 4 treatments,and the acupoint catgut embedding + AG490 group was injected intraperitoneally with 1 mg/kg of AG490 every day during the treatment period;the normal group and the model group were only grasped and fixed.Body mass was measured before and after treatment.Lipid metabolism indexes of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and serum leptin levels were measured after treatment,and the mRNA expressions of hypothalamus LepR,JAK2 and STAT3 were detected by real-time quantitative polymerase chain reaction(RT-PCR),and the protein expressions of hypothalamus LepR,JAK2 and STAT3 were detected by Western Blot.Results Before treatment,compared with the normal group,the body mass of the model group,the acupoint catgut embedding group,and the acupoint catgut embedding+AG490 group were all elevated(P＜0.01),and compared with the model group,there was no significant difference in the body mass between the acupoint catgut embedding group and the acupoint catgut embedding+AG490 group(P＞0.05).After treatment,compared with the normal group,body mass,leptin and TG,TC,LDL-C levels were increased,and mRNA and protein expression levels of LepR,JAK2,STAT3 were decreased in the model group(all P＜0.01);compared with the model group,body mass,leptin and TG,TC,LDL-C levels were decreased in the acupoint catgut embedding group,and mRNA and protein levels of LepR,JAK2,STAT3 were increased in the acupoint catgut embedding + AG490 group(all P＜0.01);compared with the acupoint catgut embedding + AG490 group,the body mass,leptin and TG,TC,LDL-C levels were decreased,and mRNA and protein levels of LepR,JAK2,STAT3 were increased in the acupoint catgut embedding group(P＜0.05 or P＜0.01).Conclusion Acupoint catgut embedding has a good effect on weight loss and lipid reduction in DIO rats,and its central mechanism may be related to the down-regulation of serum leptin level and activation of hypothalamic LepR-mediated JAK2/STAT3 pathway.

Objective To construct a measurement tool for atrial fibrillation(AF)patients'experience of catheter ablation,in order to provide quantifiable basis for improving the patients'perioperative experience.Methods From Jun 2022 to Apr 2023,literature analysis,qualitative research,Delphi expert consultation,and analytic hierarchy process were used to determine the content and weight of various indicators of the measurement tool.Results The enthusiasm of experts in 3 rounds was 100%.The authority coefficient of experts was 0.946,0.961 and 0.976.The Kendal harmony coefficients of the 2 and 3 rounds of expert consultation was 0.130 and 0.370(P＜0.001).The final measurement tool included 46 items and 5 dimensions,including operational and technical quality experience,comfort management experience,information and communication experience,emotional support experience,service process and response experience.Conclusion The preliminary construction of measurement tool for AF patients'experience of catheter ablation,which were based on the features of specialty,could not only evaluate the patients'experience accurately,but also provide a basis for targeted improvement of medical and nursing service quality.

Ubiquitination, a diverse post-translational modification, is carried out by enzymes including E1-activating enzymes, E2-conjugating enzymes, E3 ligases, and deubiquitinating enzymes (DUBs). Ubiquitin itself possesses 7 lysine residues and N-terminal methionine, allowing for the formation of polyubiquitin chains with different lengths and linkages. These chains exhibit various topologies that can be recognized by proteins containing ubiquitin-binding domain, thereby transmitting distinct cellular signals. To unravel the physiological mechanisms associated with ubiquitin, numerous ubiquitin probes have been developed. This review provides an overview of recent advancements in the field of ubiquitin probes, focusing on activity-based and affinity-based probes. Activity-based probes are designed to covalently bind to DUBs, E1s, or E3s, enabling the identification and characterization of these enzymes. Affinity-based probes, on the other hand, selectively bind to ubiquitin-binding domains, facilitating the identification of proteins that interact with ubiquitin. Moreover, this review comprehensively discusses the synthetic methodologies employed for the acquisition of ubiquitin probes. These includes meticulous discussions on the synthesis of individual monomeric modules, the establishment of isopeptide linkages, as well as the incorporation of reactive functional groups. Additionally, the review explores the emerging area of cell-penetrating ubiquitin probes and highlights their latest applications in living cells. These probes incorporate cell-penetrating peptides to enable their internalization into cells, allowing for direct visualization and manipulation of ubiquitin-modified proteins within their native environment. Overall, this review offers insights into the design, synthesis, and applications of ubiquitin probes, highlighting their significance in elucidating ubiquitin-mediated cellular processes.

Objective To investigate the effects of rhynchophylline on methamphetamine-dependent SH-SY5Y cells model and microRNA-375-3p(miR-375-3p)/embryonic lethal abnormal vision drosophila-like 4(Elavl4)expression.Methods A methamphetamine-dependent cell model by maximum safe dose induction was established.The cells were divided into normal group(complete culture medium),control group(complete culture medium+400 μmol·L-1 rhynchophylline incubated for 48 h),model group(complete culture medium+100 μmnol·L-1 methamphetamine incubated for 48 h)and experimental group(complete culture medium+400 μmol·L-1 rhynchophylline incubated for 15 min,then 100 μmol·L-1 methamphetamine incubated for 48 h).The cyclic adenosine monophosphate(cAMP)and 5-hydroxytryptamine(5-HT)expression were detected by enzyme-linked immunosorbent assay(ELISA),miR-375-3p expression was detected by quantitative real time polymerase chain reaction(qRT-PCR),and Elavl4 expression was detected by Western blot.Results The cAMP expression levels of normal group,control group,model group and experimental group were(6.33±0.93),(6.57±1.12),(10.89±1.03)and(7.81±1.32)pmol·mg-1;5-HT were(682.46±17.32),(690.31±15.09),(510.11±27.67)and(649.99±21.42)pg·mL-1;miR-375-3p expression were 1.00±0.13,1.13±0.24,3.48±0.18 and 1.58±0.19;Elavl4 expression were 1.00±0.05,0.89±0.10,0.50±0.09 and 0.90±0.11,respectively.The differences between above indicators in model group and normal group were statistically significant(P＜0.01,P＜0.05);the differences between above indicators in experimental group and model group were statistically significant(P＜0.01,P＜0.05).Conclusion This study preliminarily established a methamphetamine-dependent cell model,and also found that rhynchophylline may regulate miR-375-3p/Elavl4 expression to antagonize methamphetamine addiction.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To analyze the cognition level of health care workers(HCWs)and the management status of various levels of medical institutions towards allergy reactions to commonly used antimicrobial agents.Methods HCWs and clinical pharmacists who were related to the diagnosis and treatment of antimicrobial agents in 14 medical institutions of city-level and autonomous prefectures in Gansu Province were randomly selected for a questionnaire survey.The survey contents included respondents'basic information,criteria for judging antimicrobial allergy,awareness on procedures related to antimicrobial allergy,and antimicrobial management level of different levels of medical institutions.Results A total of 8 670 valid questionnaires from HCWs were collected,including 3 300 phy-sicians,5 024 nurses and 328 pharmacists.160,775,2 123 and 5 612 HCWs were with senior,associate,interme-diate and junior professional titles,respectively.87.66％of the HCWs received relevant training on antimicrobial management in the past two years,the proportion of HCWs from different levels of medical institutions who have received training on antimicrobial management in the past two years was statistically significant different(x2=42.668,P＜0.001).HCWs with senior professional titles had the highest proportion of receiving relevant training(93.75％),there was a statistically significant difference in the proportion of receiving antimicrobial management training among HCWs with different professional titles in the past two years(x2=69.782,P＜0.001).50.98％of HCWs were not clear about penicillin allergy,and most of whom were with junior professional titles,accounting for 68.52％.25.19％of HCWs expressed uncertainty about whether patients with penicillin allergy could use cephalosporins,225 of whom were with associate professional titles,accounting for 29.03％of the total number of HCWs with associate profe-ssional titles.6.11％of HCWs had no experience in skin test procedure;46.94％of HCWs expressed that their medical institutions had no or unclear about whether their medical institutions had an antimicrobial allergy assess-ment team.Conclusion HCWs'judgment on allergy reactions to commonly used antimicrobial agents and aware-ness on antimicrobial application is not high enough,and the overall management level of antimicrobial allergy in all levels of medical institutions is poor.The popularity of antimicrobial allergy assessment teams is not high,and there is an urgent need to strengthen supervision,management,training,et al.

Objective:Utilizing a seven-year panel data set of a targeted admission medical student cohort,this study aims to examine their career development and provide insights for retaining healthcare talent in township health centers and village clinics in the central and western rural areas of China.Method:Starting from 2015,cohorts of targeted and general clinical graduates from four medical colleges in central and western China were selected and tracked for their career progression.Results:The targeted graduates'standardized residency training and medical licensing examination pass rates were similar to those of general clinical graduates.They advanced more quickly in professional titles and positions,with 82.5%becoming attending physicians and 16.2%obtaining positions in the seventh year after graduation.However,their monthly income was significantly lower than that of general clinical graduates,and this income discrepancy expanded annually.As of December 2022,among the 493 targeted graduates who completed their contracts,38.5%stayed in grassroots positions.Of those who left,60%moved to county-level or higher public hospitals,7.9%pursued further studies,and 27.7%were unemployed.Conclusion:Targeted graduates are well-trained and advance rapidly in their careers,but their lower income significantly impacts their willingness to remain at the grassroots level.After completing their service period,about one-third of the targeted graduates choose to stay in grassroots positions.

Background The subway environment, characterized by dense crowds, relatively enclosed architectural structures, and insufficient ventilation, poses various health hazards. Population health risk attributable to subway hygiene have become an important public health issue. Objective To evaluate the current environmental hygiene of metro line X in Nanjing, and to provide a scientific basis for the prevention and control of harmful factors and the establishment of relevant standards. Methods Station halls, platforms, and carriages of Nanjing metro line X were monitored in March 2023. Six stations were selected by stratified sampling, and monitored once during the morning peak hours (9:00—11:00). Carriage monitoring was conducted after a full day of operation (21:00—22:00). The monitoring indicators included physical factors such as temperature, relative humidity, wind speed, illuminance, and noise (A-weighted); air quality factors such as carbon dioxide (CO₂), carbon monoxide (CO), respirable particulate matter (PM₁₀), fine particulate matter (PM_2.5), ammonia (NH₃), formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), ozone (O₃), total bacterial count, and total fungi count; hygiene status of the inner surface of the central air conditioning ventilation system, such as dust accumulation, total bacterial count, and total fungi count; supply air, such as PM_10, PM_2.5, total bacterial count, and total fungi count; and surface microorganisms on objects, such as total bacterial count, total fungi count, coliform bacteria, and Staphylococcus aureus. Results were evaluated and discussed according to Hygienic indicators and limits for public places (GB 37488-2019) and Hygienic specification of central air conditioning ventilation systems in public buildings (WS 394-2012). Results The environmental temperature medians (P₂₅, P₂₅) in the platforms and carriages of Nanjing metro line X were 20.7 (19.95, 21.65) ℃ and 21.8 (19.80, 35.80) °C, respectively, which exceeded the standard limits. The relative humidity and noise level in the carriages were 38.80% (24.6%, 46.3%) and 79.50 (76.25, 82.00) dB, respectively, failing to meet the national health standards. The total fungi count in supply air in 22.2% of the monitoring points exceeded the standard value. Coliform bacteria and Staphylococcus aureus were detected on the surfaces of some high-touch objects, with the bathroom faucet being the most severely contaminated. The medians (P₂₅, P₂₅) of temperature [21.8 (19.8, 35.8) ℃], wind speed [0.48 (0.39, 1.02) m·s⁻¹], noise [79.5 (76.25, 82.00) dB, and CO₂ content [0.079% (0.070%, 0.091%)] in the carriages were higher than those in the station halls and platforms (P<0.05). There were significant differences in microclimate, air particulate matter, and air microbial levels between urban and suburban stations (P<0.05); the concentrations of PM₁₀ [0.076 (0.046, 0.079) mg·m⁻³)] and PM_2.5 [0.063 (0.044, 0.068) mg·m⁻³)] in suburban stations were 2 times higher than those of urban stations. The temperature [21.60 (20.45, 21.80) ℃], humidity [45.20% (40.95%, 50.10%)], CO₂ [0.100% (0.100%, 0.825%)], and PM₁₀ concentration [0.070 (0.041, 0.080) mg·m⁻³] in transfer stations were all significantly higher than those in non-transfer stations (P<0.05). The temperature at stations was significantly correlated with the CO₂ content (r_s=0.6107, P<0.001), the concentration of air particulate matter and the content of air microorganisms were positively correlated with the relative humidity (P<0.05), and the air PM₁₀ and PM_2.5 concentrations were positively correlated with the total bacterial count and the total fungi count (P<0.05). There was a significant positive correlation between the total bacterial count and the total fungi count on the inner surface of the air duct (r_s=0.5877, P<0.05). The concentrations of PM₁₀ and PM_2.5 in supply air were positively correlated (r_s=0.9635, P<0.001), and both were also positively correlated with the total bacterial count in supply air (r_s=0.6848 and 0.6511, P=0.002 and 0.003). Conclusion All chemical factors of metro line X in Nanjing meet the national standards, while physical factors (temperature, relative humidity, wind speed, and noise) exceed the standards, and coliform bacteria and Staphylococcus aureus are detected on the surfaces of bathroom faucets and carriage poles. It is advisable to reinforce microclimate management and noise reduction measures in carriages, while ensuring regular cleaning and disinfection of public facilities and equipment.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Objective:To investigate the pathogenic role and possible mechanism of NADPH oxidase 4 (Nox4) in type 1 diabetic keratopathy mouse models.Methods:Forty Nox4 knockout ( Nox4-/-) heterozygous male mice were selected and 120 age- and sex-matched wild-type C57BL/6 ( Nox4+ /+ ) mice were selected as controls. Nox4-/- and Nox4+ /+ mice were randomized into diabetic group (DM group) and non-DM group by random number method.Type 1 DM model was established in DM groups by intraperitoneal injection of streptozotocin.The DM and non-DM groups of Nox4+ /+ mice were randomized into regular feed group and Nox4 inhibitor GKT137831 (GKT) supplementary feed group by random number method.At 16 weeks after modeling, tear secretion of mice in different groups was measured by the phenol red thread test.Corneal epithelial integrity was evaluated by fluorescent staining.Changes in corneal never fiber density were observed by the in vivo laser scanning confocal microscopy.Reactive oxygen species (ROS) products in corneal epithelium were assayed by CellROX staining.The expressions of E-Cadherin and nuclear factor-κB (NF-κB) proteins were detected by immunofluorescence staining.Central corneal nerve fiber density was examined by flatmount staining with TUBB3 antibody.The use and care of laboratory animals complied with ARVO statement.The study protocol was approved by Laboratory Animal Care Committee of Xi'an Jiaotong University (No.XJTULAC201301). Results:In Nox4+ /+ mice, the tear secretion was (2.40±1.18)mm/minute in DM group, which was significantly less than (5.30±1.02)mm/minute in non-DM group ( P<0.01).The tear secretion was (4.19±0.63)mm/minute in DM group of Nox4-/- mice, which was significantly more than that in DM group of Nox4+ /+ mice ( P<0.05).Significant difference was found between (2.23±0.83)mm/minute of regular feed group and (4.02±0.71)mm/minute of GKT supplementary feed group ( P<0.01).In Nox4+ /+ mice, the DM group showed significantly increased corneal staining score, reduced corneal nerve fiber density, increased fluorescence intensity of ROS in corneal epithelium, weakened fluorescence intensity of E-Cadherin protein expression, and enhanced fluorescence of NF-κB protein expression compared with non-DM group.In Nox4-/- mice and mice fed with GKT supplementary feed, the increased fluorescence of ROS and decreased fluorescence of E-Cadherin protein expression were seen in the corneal epithelium of the DM groups compared with non-DM groups.In Nox4-/- mice and mice fed with GKT supplementary feed, NF-κB protein fluorescence was weak in corneal epithelial cells in DM groups, which was similar to that in non-DM groups.Immunofluorescence staining of corneal flatmount showed that the density of TUBB3-stained nerve fibers in DM group of Nox4+ /+ mice was significantly lower than that in non-DM group of Nox4+ /+ mice, and there was no significant reduction of nerve fibers in the corneal stromal layer in DM group of Nox4-/- mice or mice fed with GKT supplementary feed. Conclusions:Nox4 is involved in the pathogenic process of diabetic keratopathy, and its mechanism may be related to oxidative stress-induced aggregation of ROS products and activation of NF-κB-mediated inflammatory responses.