ObjectiveTo explore the clinical efficacy and safety of Da Chaihutang （DCH） for the treatment of sepsis with Yang syndrome. MethodsA total of 70 patients suffering from sepsis with Yang syndrome were randomly divided into an observation group and a control group， with 35 cases in each group. They both received standard Western medicine treatment. The observation group was additionally given a dose of DCH， which was boiled into 100 mL and taken twice. The control group was additionally given an equal volume and dosage of warm water. The intervention lasted for three days. The 28-day all-cause mortality and the changes in the following indicators before and after intervention were compared between the two groups， including sequential organ failure assessment （SOFA）， acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score，white blood cell （WBC），the percentage of neutrophils （NEU%），C-reactive protein （CRP），procalcitonin （PCT），alanine transaminase （ALT），aspartate transaminase （AST），total bilirubin （TBil），creatinine （Cr），blood urea nitrogen （BUN），acute gastrointestinal injury （AGI） grade，gastrointestinal dysfunction score （GDS），serum intestinal fatty acid-binding protein （iFABP）， citrulline （CR），platelet （PLT），prothrombin time（PT），activated partial thromboplastin time （APTT），fibrinogen （Fib），international normalized ratio （INR），and D-dimer （D-D）. ResultsThere was no significant difference between the two groups regarding 28-day all-cause mortality. After the intervention，SOFA，WBC，PCT，and Cr were significantly decreased， and PLT was significantly increased in the control group （P<0.05）. SOFA，APACHE Ⅱ，NEU%，CRP，PCT，ALT，AST，Cr，BUN，AGI grade，GDS，and serum iFABP and CR were significantly improved in the observation group （P<0.05）. After the intervention，APACHE Ⅱ，PCT，AGI grade，GDS，and serum iFABP in the observation group were significantly lower than those in the control group ，while CR and PLT were higher （P<0.05，P<0.01）. There were significant differences regarding the gap of SOFA，APACHE Ⅱ，AST，TBil，AGI grade，GDS，iFABP，CR， and PLT between the two groups （P<0.05，P<0.01）. There were slight differences regarding PT，APTT，Fib，INR，and D-D between the two groups，which were in the clinical normal range. ConclusionOn the basis of Western medicine， DCH helped to reduce sepsis severity and improved multiple organ dysfunction with high clinical efficacy and safety， but further research on its impact on the prognosis of patients with sepsis is still required.

OBJECTIVE To evaluate the impact of the specialized centralized procurement policy for insulin on daily cost and affordability of insulin， and provide data support for the enhancement of relevant policies. METHODS In this research， the insulin purchasing data were obtained from provincial centralized procurement platforms in provinces before and after the specialized centralized procurement of insulin （October-December 2021 and October-December 2022）， and the cost variations of insulin before and after the centralized procurement were analyzed by the defined daily dose cost （DDDc） of various types of insulins. The changes in the affordability of various types of insulins before and after the specialized centralized procurement were evaluated， using the percentage of annual expenditure on various types of insulins relative to annual per capita disposable income （i.e. the proportion of annual expenditure） as an indicator. RESULTS After the specialized centralized procurement， DDDc of various types of insulins decreased by 20.7%-71.8%， with an average reduction of 45.7%. Moreover， the reduction in DDDc for third-generation insulin exceeded that for second-generation insulin. The reduction in the proportion of annual expenditure on insulin ranged from 24.3% to 73.4%， with an average decrease of 48.5%. Premixed insulin analogs experienced the greatest reduction （73.4%）. Following the specialized centralized procurement， DDDc of insulin decreased in all provinces. Except for Guangxi （10.2%）， the average proportion of annual expenditure on insulin in the remaining provinces dropped to below 10%. CONCLUSIONS The specialized centralized procurement policy for insulin has significantly reduced insulin costs and improved affordability， thereby alleviating the economic pressure on patients with diabetes. There are notable cost disparities among provinces and among insulin categories， which require attention.

Objective: To examine the association between the left behind status and health risk behaviors (HRB) among adolescents, so as to provide empirical evidence for identifying high risk groups and developing intervention measures for HRB. Methods: From October to November 2023, by using a combination of convenient sampling and cluster sampling,14 964 adolescents from 6 schools in a county level city in Hubei Province (3 junior high schools and 3 senior high schools) and 7 schools in a county level city in Hunan Province (all junior high schools) were selected as the research subjects. The adolescents were divided into non-left-behind, father absent, mother absent, and both parents absent groups based on their left behind status. A self designed adolescent HRB questionnaire was utilized to investigate the prevalence of 12 types of HRBs and their co-existence among the subjects. Multifactorial Logistic regression and unordered multinomial Logistic regression analyses were used to explore the association between the left behind status of adolescents and the occurrence of individual HRBs as well as the co-existence of multiple HRBs. Results: After controlling for gender, age, only child, and subjective socioeconomic status, the results of the multiple factor Logistic regression analysis showed that having father in absence for working was positively associated with screen use long time on school days ( OR= 1.15, 95%CI =1.05-1.26) and rest days ( OR=1.16, 95%CI =1.06-1.26); having mother in absence for working was significantly associated with increased risks of smoking ( OR=1.68, 95%CI =1.22-2.32), spending long time on screen during school days ( OR= 1.19, 95%CI =1.00-1.41)and rest days ( OR=1.36, 95%CI =1.16-1.59), skipping breakfast ( OR=1.20, 95%CI =1.03-1.39), skipping dinner ( OR=1.20, 95%CI =1.01-1.43), not eating fruit ( OR=1.34, 95%CI =1.12-1.61), and consuming sugar sweetened beverages ( OR=1.30, 95%CI =1.09-1.55); having both parents in absence for working was positively associated with screen use on rest days ( OR=1.51, 95%CI =1.38-1.65), skipping dinner ( OR=1.15, 95%CI =1.04-1.27), not eating fruit ( OR=1.80, 95%CI =1.62-1.99),and non suicidal self injury ( OR=1.16, 95%CI =1.04-1.29), and negatively associated with fast food consumption ( OR=0.72, 95%CI =0.65-0.79)(all P <0.05).The results of unordered multiclass Logistic regression analysis showed that mother absence for working was associated with an increased risk of moderate and high co-occurrence of HRBs ( OR= 1.25, 95%CI=1.06-1.47; OR=1.67, 95%CI =1.30-2.13), both parents absence for working was also positively correlated with a high cooccurrence risk of HRBs ( OR=1.29, 95%CI =1.11-1.50) (all P <0.05). Conclusion Father absence for working is only related to adolescents screen time, while adolescents with mother absence or both parents absent for working are priority groups for HRB prevention.

BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective: To explore the facilitating and hindering factors of mental health promotion activities in junior and senior high schools from teachers perspectives, as well as coping strategies, so as to provide evidence for implementing teacher led mental health promotion programs. Methods: From September 2023 to September 2024, by using purposive sampling method, 5 junior high schools, 5 regular high schools, 2 vocational high schools in four provinces and municipalities (Tianjin, Shanxi, Shandong, and Jiangxi) were selected. A total of 92 teachers (78 homeroom teachers and 14 full time or part time psychological counselors) were interviewed using semi structured focus group discussions (one session per school, totaling 12 sessions). Thematic analysis was applied to code and analyze the interview transcripts. Results: The implementation of mental health promotion activities in middle schools was influenced by three levels: teachers, schools and society. Specifically, teachers exhibited a high support low capability phenomenon (81 participants supported conducting such activities, but 71 felt lacking in professional capacity); activity effectiveness and support systems were imbalanced (42 mentioned significant effects, while 78 reported insufficient support); there was a mismatch between student demand and activity content (9 mentioned students had psychological needs, but 11 indicated existing activities failed to meet these needs); administrative support and sustainability showed disparities (14 believed sufficient administrative support existed, while 37 noted sustainability issues); parental awareness and participation remained inadequate (11 highlighted parents need for mental health knowledge, and 37 perceived insufficient understanding of psychological issues among parents). Effective strategies included enhancing teachers effectiveness, providing essential skill training, focusing on the needs of teenagers,enhancing program sustainability, and eliminating misconceptions about mental health among parents. Conclusion Mental health promotion activities in junior and senior high schools should focus on enhancing teachers skills, improving activity sustainability, reducing stigma among parents, and establishing a collaborative network for school based mental health promotion.

Objective To compare the difference in the efficacies of arthroscopic microfracture operation for talar osteochondral injuries with hyperuricemia and non-hyperuricemia,and to explore the correlation be-tween blood urate level and efficacy.Methods Fifty-three patients with talar osteochondral lesions meeting the inclusion and exclusion criteria from February 2015 to August 2021 were selected as the research subjects and divided into the hyperuricemia group (22 cases) and non-hyperuricemia group (31 cases) according to whether or not the preoperative blood uric acid level exceeding 420 μmol/L.The joint range of motion (ROM),visual analog scale (VAS) score,American Foot and Ankle Surgery Society (AOFAS) score,mag-netic resonance score of cartilage repair tissue (MOCART) score and postoperative satisfaction before and af-ter surgery were compared between the two groups.Results The preoperative blood uric acid level in the hy-peruricemia group was higher than that in non-hyperuricemia group,and the difference was statistically signif-icant[(504.35±86.40)μmol/L vs.(332.56±45.80)μmol/L,P<0.05].The ROM score,VAS score and AOFAS score in postoperative 1 year follow up and last follow up in the two groups were significantly im-proved compared with before operation (P<0.001).The AOFAS scores before operation,in postoperative 1 year and postoperative last follow up in the hyperuricemia group were lower than those in the non-hyperurice-mia group (P<0.05).The VAS scores before operation and postoperative last follow up in the hyperuricemia group were higher than those in the non-hyperuricemia group (P<0.05).The uric acid level was negatively correlated with the postoperative AOFAS score (r2=0.076,P=0.041).The MOCART score in postopera-tive last follow up in the hyperuricemia group was lower than that in the non-hyperuricemia group,and the difference was statistically significant (P<0.05).The cartilage defect repair and filling degree and the fusion of repaired tissue with adjacent cartilage had statistical differences between the hyperuricemia group and non-hyperuricemia group (P<0.05).Conclusion Arthroscopic microfracture operation in treating talar osteo-chondral injuries has good clinical effect,the postoperative clinical effect in the patients with complicating hy-peruricemia is lower than that in the patients with non-hyperuricemia and the blood uric acid level is negative-ly correlated with the AOFAS score after microfracture surgery.

Objective:To establish a cell line stably expressing the transient receptor potential melastatin 2(TRPM2)channel for screening TRPM2 inhibitors based on PiggyBac transposition system.Methods:A plasmid PiggyBac-human TRPM2(pPB-hTRPM2)eukaryotic expression vector was constructed using PiggyBac transposition system.The plasmid and a helper plasmid were co-transfected into HEK293T cells to express TRPM2,which was identified by fluorescence and patch-clamp assays.The high throughput screening performance was assessed with the Z'factor.Calcium imaging and patch clamp techniques were employed to assess the initial activity of eleven compound molecules,confirming the inhibitory effects of the primary molecules on TRPM2.The protective effect of the screened compounds on damaged cells was validated using the oxygen-glucose deprivation/reperfusion(OGD/R)injury model and CCK-8 kit.The level of cellular reactive oxygen species(ROS)was detected by flow cytometry.The neuroprotective effects of the compounds were evaluated using a transient middle cerebral artery occlusion(tMCAO)mouse model.Results:The HEK293T cells transfected with pPB-hTRPM2-EGFP showed high TRPM2 expression.Puromycin-resistant cells,selected through screening,exhibited robust fluorescence.Whole-cell patch results revealed that induced cells displayed classical TRPM2 current characteristics comparable to the control group,showing no significant differences(P＞0.05).With a Z'factor of 0.5416 in calcium imaging,the model demonstrated suitability for high-throughput screening of TRPM2 inhibitors.Calcium imaging and electrophysiological experiments indicated that compound 6 significantly inhibited the TRPM2 channel.Further experiments showed that 1.0 μmol/L of compound 6 enhanced cell viability(P＜0.05)and reduced the level of ROS(P＜0.05)of SH-SY5Y under OGD/R injury.0.3 and 1.0 mg/kg of compound 6 reduced the cerebral infarction volume in tMCAO mice(both P＜0.05).Conclusions:A stable TRPM2 gene expressing cell line has been successfully established using PiggyBac gene editing in this study.TRPM2 channel inhibitors were screened through calcium imaging and patch clamp techniques,and an inhibitor compound 6 was identified.This compound can alleviate cell damage after OGD/R by reducing cellular ROS levels and has a protective effect against cerebral ischemia-reperfusion injury in mice.

Objective:To investigate the application effects of a novel framework: the external septal retention bionic framework in East Asian rhinoplasty.Methods:A retrospective analysis was performed based on the clinical data of the patients who received treatments in Department of Plastic and Aesthetic ( Burn) Surgery, the Second Xiangya Hospital, Central South University from January 2022 to July 2023 using an external septal retention bionic framework with autologous costal cartilage rhinoplasty. The patients were all treated with a V-shaped incision at the nasal columella, which continued to both sides of the nose to form a bird-shaped incision. During the operation, the sixth or seventh costal cartilage was sculpted to form the nasal columella support grafts (sturt), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft were implanted in a mortise-and-tenon joint structure to form a septum bionic retained external stent in order to lengthen the nasal columellar column and strengthen the septum. A capsular graft was used to shape the tip of the nose and the rectus abdominis fascia was covered to soften the tip of the nose, and the shield grafts were used to fill out the subnasal lobules. A bulb was sculpted, shaped and implanted in the dorsal space to elevate the nasal dorsum. To observe the postoperative results and complications, a postoperative satisfaction survey was completed using the rhinoplasty outcome evaluation (ROE) and the visual analogue scale (VAS) with regular follow-up. Comparison of preoperative and postoperative scale scores was performed using paired samples t-test. Nasal stent stability was assessed by measuring the patients’ preoperative and postoperative nasolabial angle and nasal tip protrusion. The comparison of preoperative and postoperative nasolabial angle was performed using the paired-sample t-test, and the comparison of nasal tip protrusion was performed using the Wilcoxon signed rank-sum test, P<0.05 considered a statistically significant difference. Results:A total of 33 patients were enrolled, including 4 males and 29 females, with average age of 23.8 years(15-42 years). The follow-up period is (14.52 ± 4.72) months (3 to 21 months). Thirty-three patients recovered well after surgery, and no short-term complications such as infection or bleeding occurred. The patients' nasal aesthetic problems such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and rounded shield of the nasal tip were improved after surgery. Satisfaction survey results: ROE and VAS scores were significantly higher than those before surgery, which were [(17.92±2.56) vs.(12.78±3.14)] and [(8.08±1.66)vs(5.15±1.99)], ( P<0.05), 87.9% (27/33)of the patients were satisfied with the aesthetic and functional outcomes of the nose. Comparisons of nasolabial angle [(87.28±2.58)° vs. (97.64±1.95)°] and tip protrusion [1.88 (1.78, 1.95) cm vs. 2.16(2.01, 2.32) cm] measurements between preoperative and postoperative period of the 33 patients, the differences were statistically significant ( P<0.05). Conclusion:Rhinoplasty for East Asians employs an external septal retention bionic framework to retain the nasal septum. This technique can avoid septal cartilage resorption caused by compression of grafts transplanted in the future, and cause less damage to the anatomy and physiology of the nose. The framework is relatively easy to construct, with a stable and strong stent, and good patient satisfaction. It can achieve a more desirable aesthetic effect of the nose.