Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.

Bacterial resistance and excessive inflammation are common issues that hinder wound healing.Antimicrobial peptides(AMPs)offer a promising and versatile antibacterial option compared to traditional antibiotics,with additional anti-inflammatory properties.However,the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation.TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs.Therefore,in this study,a composite hydrogel(HAMA/t-GL13K)was prepared via the photocross-linking method,in which tFNAs carry GL13K.The hydrogel was injectable,biocompatible,and could be instantly photocured.It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS.Thereby,the hydrogel inhibited bacterial infection,shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring.The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

Objective:To observe the changes of 5-hydroxytryptamine (5-HT) level in myocardial tissue of pre-treatment mice with sepsis myocardial injury by electroacupuncture at Zusanli point, and to explore the protective effect and possible mechanism of electroacupuncture on myocardial injury in sepsis.Methods:Twenty male C57BL/6 mice were divided into control group (NC group), sepsis model group (LPS group), electroacupuncture group (EA group) and electroacupuncture + fluoxetine group (EA+FLU group) by random number table method, with 5 mice in each group. The myocardial injury model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 g/L. The NC group was intraperitoneally injected with the same amount of normal saline. 3 days before mold making, EA group and EA+FLU group were electrocuted at Zusanli point on both sides for 15 minutes, once a day for 3 days. The EA+FLU group was intraperitoneally injected fluoxetine 1.4 g/L before electroacupuncture. After modeling, the cardiac histopathological changes were observed by hematoxylin-eosin (HE) staining. The serum levels of inflammatory cytokines interleukins (IL-6, IL-8), and tumor necrosis factor-α (TNF-α), the content of 5-HT in myocardial tissue, myocardial injury markers MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTnI), and the levels of adenosine triphosphate (ATP) and lactic acid in myocardial tissue were detected. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expressions of 5-hydroxytryptamine transporter (5-HTT), hexokinase 2 (HK2) and glucose transporter 4 (GLUT4) in myocardial tissue. GLUT4 expression in myocardial tissue was detected by immunofluorescence assay.Results:Compared with NC group, the serum levels of IL-6, IL-1β and TNF-α, myocardial 5-HT content, myocardial tissue injury markers CK-MB, cTnI in LPS group and EA+FLU group were significantly increased. Compared with LPS group, the above indexes in EA group were significantly decreased [IL-6 (ng/L): 443.03±156.16 vs. 19?843.75±0.00, IL-1β (ng/L): 75.72±10.60 vs. 894.66±350.88, TNF-α (ng/L): 46.17±4.71 vs. 533.01±170.58, 5-HT (μg/L): 161.19±5.96 vs. 244.74±14.38, CK-MB (ng/L): 468.21±12.46 vs. 662.02±22.54, cTnI (ng/L): 0.83±0.05 vs. 0.99±0.08, all P < 0.05]. Compared with NC group, the levels of ATP in myocardium of LPS group, EA group and EA+FLU group were significantly decreased, the levels of lactic acid in myocardium were significantly increased. Compared with LPS group, the level of ATP in myocardium of EA group was significantly increased, the level of lactic acid in myocardium was significantly decreased [ATP (mmol/L): 0.10±0.01 vs. 0.08±0.01, lactic acid (mmol/L): 56.03±1.07 vs. 72.45±4.32, both P < 0.05]. Compared with NC group, the mRNA expression of HK2 in myocardium of LPS group was significantly increased, and the mRNA expressions of GLUT4 and 5-HTT were significantly decreased. Compared with LPS group, the mRNA expression of HK2 in myocardium of EA group was significantly decreased, the mRNA expressions of GLUT4 and 5-HTT were significantly increased [HK2 mRNA (relative expression level): 0.73±0.19 vs. 1.82±0.57, GLUT4 mRNA (relative expression level): 1.00±0.33 vs. 0.47±0.18, 5-HTT mRNA (relative expression level): 1.18±0.31 vs. 0.38±0.15, all P < 0.05]. Compared with NC group, the fluorescence intensity of GLUT4 in LPS group and EA+FLU group were significantly decreased. Compared with LPS group, the fluorescence intensity of GLUT4 in EA group was significantly enhanced. Conclusions:Electroacupunctureat Zusanli can reduce the content of 5-HT in myocardial tissue of sepsis mice, and its regulatory mechanism may be related to the regulation of 5-HTT and GLUT4.

Sepsis,a syndrome characterized by organ dysfunction caused by infection,exhibits high incidence and mortality.The pathogenesis of sepsis is complex and involves a cascade of immune reactions,with no specific drugs currently available.Sepsis is mainly treated with Western medical supportive therapies such as antibiotics,hemodynamic management,and mechanical ventilation.However,the occurrence of immune cas-cades significantly increases patients'vulnerability to secondary infections,leading to septic shock and unfavor-able prognoses.International consensus indicates that initiating dynamic monitoring of patients'immune function within 48 h post-sepsis diagnosis can effectively decelerate sepsis progression.Extensive studies have indicated that macrophages,serving as the first line of defense in the innate immune system against pathogens,play a vital role in treating immune system disorders by regulating macrophage polarization and the ratio of cytokines activated.Mitophagy,a hot topic in recent years,has increasingly been shown to play a crucial role in regulating inflammatory signal transduction.Promoting mitophagy during the stage of cytokine storm can mitigate uncontrolled infection and excessive inflammation in sepsis,and inhibiting mitophagy during immunosuppression can enhance host immunity,facilitate bacterial clearance,and improve the survival rate of patients.The idea of treating dis-ease before its onset in traditional Chinese medicine(TCM)coincides with the current consensus among sepsis experts on prevention and interception.The TCM therapies such as extracts of Chinese medicine decoction pieces,TCM compound prescriptions,and acupuncture and moxibustion have the effects of clearing heat and detoxifying,activating blood and resolving stasis,reinforcing healthy qi and consolidating root,and purging.These approa-ches dynamically regulate the levels of mitophagy-related proteins,such as phosphatase and tension homology-induced putative kinase 1,Parkin-E3 ubiquitin protein ligase,light chain 3,and p62,while maintaining a suitable ratio between M1 and M2 macrophages.Consequently,they effectively prevent,halt,or even reverse the progression of sepsis,offering a novel perspective on sepsis management by emphasizing prevention before disease onset and controlling development of existing disease.

Objective:To investigate the application of combined deep learning and radiomic features derived from enhanced arterial phase CT imaging with clinical data to differentiate between T2 and T3 staging in patients with esophageal cancer.Methods:A retrospective study was conducted using clinical and CT data from 388 patients with pathologically confirmed esophageal cancer treated at The First Affiliated Hospital of Wannan Medical College between May 2015 and April 2024.The dataset was randomly divided into a training set(271 cases)and validation set(117 cases)in a 7:3 ratio.Radiomic and deep learning features were extracted from enhanced arterial phase CT images.The least absolute shrinkage and selection operator algorithm was employed for feature reduction and selection,leading to the development of radiomic(Radscore)and deep learning(Deepscore)scores.Univariate and multivariate Logistic regression analyses were conducted to identify independent risk factors,and clinical,radiomic,deep learning,and combined models were constructed.A nomogram was gener-ated for the combined model.The diagnostic performance of the models was evaluated using the area under the receiver operating charac-teristic curve(AUC)and compared using the DeLong test.Clinical net benefit was assessed through decision curve analysis,and model calib-ration was evaluated using calibration curves.Results:Nine radiomicand 12 deep learning features were selected after dimensionality reduc-tion.Multivariate Logistic regression identified tumor length,boundary,Radscore,and Deepscore as independent risk factors for distinguish-ing between T2 and T3 staging.In the training set,the AUC of the combined model was 0.867,which was significantly higher than that of the clinical(0.774,P<0.001),radiomic(0.795,P<0.001),and deep learning(0.821,P=0.001)models.In the validation set,the AUC of the com-bined model was 0.810,which was significantly higher than that of the clinical(0.653,P=0.002),radiomic(0.719,P=0.033),and deep learn-ing(0.750,P=0.009)models.The decision curve analysis indicated that the combined model provided the highest clinical benefit in both datasets.The calibration curves demonstrated a good fit for both datasets(P=0.084,0.053).Conclusion:The integration of deep learning and radiomic features obtained from enhanced arterial phase CT images with clinical data offers a reliable method for accurately distinguishing between preoperative T2 and T3 staging in esophageal cancer,thereby supporting clinical decision-making for treatment planning.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Background The complex and diverse occupational disease hazards in automobile manufacturing industry pose high occupational health risks to workers. Objective To explore the methods that can accurately reflect the workplace health risk grade of automobile manufacturing enterprises, and to guide enterprises to practice risk classification management. Methods Comprehensive index method, International Commission on Mining and Metals occupational health risk assessment method (ICMM method), and risk index method were used toassess health risks of occupational disease hazards in major workstations such as welding, polishing, and painting in three automobile manufacturing enterprises in Hunan Province. Kappa consistency test was used to test the grading results of the three assessment methods. The re-examine results and detection rate of contraindications of occupational health examinations in the past three years were used to verify the assessment results. Results The results of comprehensive index method showed that the hazards of each selected workstation in enterprises A and B were evaluated as grade 2-3, among which NO₂ in enterprise A was grade 3, and welding fume, NO₂, and formaldehyde in enterprise B were all grade 3. The hazards of each selected workstation in enterprise C were grade 3-4, among which NO₂ and benzene in were grade 4, and welding fume, manganese and its compounds, grinding wheel dust, and xylene were grade 3. The hazards evaluated by ICMM quantitative method were grade 2 and grade 5, among which manganese and its compounds in enterprise A and welding fume, grinding wheel dust, and benzene series in enterprise C were graded as grade 5. The hazards evaluated by risk index method were grade 1-4, among which manganese and its compounds in enterprises A and B were grade 3, and manganese and its compounds and benzene in enterprise C were grade 4. The Kappa value between comprehensive index method and ICMM method was 0.084 (P>0.05), that between comprehensive index method and risk index method was −0.046 (P>0.05), and that between ICMM method and risk index method was 0.014 (P>0.05), indicating poor consistency. By comparing the results of occupational health surveillance with the results of occupational health risk assessment, one worker was found to have occupational contraindication of manganese exposure and 1 worker was found to have excessive manganese in hair in enterprise A. However, the comprehensive index method graded low risk for manganese and its compounds in enterprise A and the result is conservative. The key workstations identified by ICMM method were consistent with the occupational health examination results, but the assessment grades were all extremely high risk, and the results were too strict. One worker was found to be contraindicated to welding fumes, and 2 polishers were found to have severe mixed pulmonary ventilation dysfunction in enterprise C. Mild and moderate pulmonary ventilation dysfunction was found to be common in welding and polishing workstations in each enterprise. The assessment results of welding fumes and grinding wheel dust by the risk index method were negligible risks, which were inconsistent with the occupational health examination results. Conclusion The comprehensive index method, ICMM method, and risk index method can basically identify workstations with serious occupational hazards, but they have certain limitations and applicability. In general, the evaluation results of the comprehensive index method were generates more consistent with the results with occupational health surveillance than the other two methods, is more comprehensive and objective in consideration, and is more suitable for health risk assessment of automobile manufacturing enterprises.

Background The mining of non-coal underground mines may come into contact with various types of dust, such as lead, zinc, copper, and non-metallic minerals. Dust of various kinds commonly exists in all aspects of mining and selection, and is one of the main occupational hazard groups in non-coal underground mines. Objective To compare the application of two risk assessment methods in the occupational health risk assessment of productive dust in non-coal underground mines, and to provide a reference for the selection of dust hazard health risk assessment methods and the management of dust hazards in non-coal mines. Methods A field investigation of the dust hazards of three typical non-coal underground mining enterprises (lead-zinc mines, copper mines, and fluorite mines) was carried out, and the comprehensive index method and the occupational health risk assessment method from the International Council on Mining and Metals (ICMM) were used to perform risk assessments. The comprehensiveindex method considers the following factors: dust monitoring data, the aerodynamic diameter of dust, hazard control measures, occupational health management, daily usage, and daily exposure time to determine exposure levels. The ICMM method determines the risk level based on the consequences caused by dust, exposure probability, exposure time, and uncertainty coefficient. Kendall consistency test was used to compare agreement between the results generated by the two methods. Results The results generated by the comprehensive index method were as follows: level 3 (medium risk) or level 4 (high risk) for silica dust or lead dust; level 1 (negligible risk) or level 2 (low risk) for other dust (dust with free SiO₂ content<10% and containing lead, zinc, and copper, using other dust limit values for comparison), fluorspar mixed dust, fluorine and its compounds, zinc oxide, and copper dust. The risk levels graded by the ICMM method were as follows: level 4 (very high risk) and level 3 (high risk) for exposure to silica dust and lead dust, respectively, and level 1 (tolerable risk) or level 2 (potential risk) for exposure to other dust (dust with free SiO₂ content <10% and containing lead, zinc, and copper, using other dust limit values for comparison), fluorspar mixed dust, fluorine and its compounds, zinc oxide, and copper dust. The consistency level between the results graded by the two methods was very high (Kendall W coefficient=0.974, P < 0.05). Conclusion For the occupational health risk assessment of productive dust in non-coal underground mines, the consistency level of risk assessment results between the ICMM method and the comprehensive index method is very high. The ICMM method is more convenient to operate and should be preferred in assessing health risks of dust hazard in non-coal underground mines.

Objective: An isochronous substitution model was established to explore the association and substitution effect between college students 24 hour activity behavior and physical health, so as to provide specific activity behavior suggestions for college students to improve their physical health. Methods: A stratified random cluster sampling method was used to conduct physical fitness tests and 24 hour activity behavior surveys among 2 794 college students in 12 colleges and universities in Tianjin.Time spent on sedentary behavior(SB), light intensity physical activity(LPA), moderate to vigorous physical activity(MVPA) and sleep(SLP) time. The isochronous method of components was used to explore the relationship between 24 h activity behavior and physical health. Results: Except for 50 m running, MVPA was negatively correlated with BMI Z ( β =-0.62, P <0.05), but positively correlated with other physical fitness indexes ( β =0.34~274.23, P <0.05). LPA was not associated with lung capacity, sitting forward flexion and 50 m running, and negatively correlated with other physical fitness indexes ( β =-14.30- -0.19, P <0.05). SB was negatively correlated with most physical fitness indexes ( β =-11.57- -0.33, P <0.05), but positively correlated with BMI Z ( β =0.45, P < 0.05 ). In addition to lung capacity, SLP was positively correlated with BMI Z , total physical fitness score,1 minute sit-ups, pull ups, 800/1 000 m running, sitting forward flexion, and 50 m running ( β =0.27-11.21, P <0.05), but negatively correlated with long jump ( β =-0.10, P <0.05）. Isochronous substitution showed that the adverse effects of 30 min/d SB and LPA substitution of MVPA were much greater than the beneficial effects of MVPA substitution for corresponding behaviors (total physical score: SB, -0.58 vs 0.47 points; LPA, -0.50 vs 0.38 points). Conclusion MVPA and SLP have been found to have a positive effect on physical fitness among college students. Therefore, in the process of improving the physical health of college students, ensuring adequate sleep, improving MVPA and reducing SB as much as possible may be one of the effective methods.

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.