Autophagy, a highly conserved cellular degradation mechanism, maintains intracellular homeostasis by removing damaged organelles and abnormal proteins. Its dysregulation is closely associated with various diseases. Autophagy-related protein 12 (ATG12), a core member of the ubiquitin-like protein family, covalently binds to ATG5 through a ubiquitin-like conjugation system to form the ATG12-ATG5-ATG16L1 complex. This complex directly regulates the formation and maturation of autophagosomes, making ATG12 a key molecule in the initiation of autophagy. Recent studies have revealed that ATG12 functions extend far beyond the classical autophagy context. It promotes apoptosis by binding to anti-apoptotic proteins of the Bcl-2 family (e.g., Bcl-2 and Mcl-1) and enhances host antiviral immunity by regulating the NF-κB and interferon signaling pathways. Moreover, ATG12 deficiency can lead to mitochondrial biogenesis impairment, energy metabolism disorders, and substrate-dependent metabolic shifts, underscoring its pivotal role in cellular metabolic homeostasis. At the disease level, dysregulation of ATG12 expression is closely linked to tumorigenesis and cancer progression. By modulating the dynamic balance between autophagy and apoptosis, ATG12 influences cancer cell proliferation, metastasis, and chemoresistance. Notably, ATG12 is abnormally overexpressed in multiple cancers, including breast, liver, and gastric cancer, highlighting its potential as a therapeutic target. Furthermore, in neurodegenerative diseases such as Parkinson’s disease, ATG12 mitigates protein toxicity by enhancing mitochondrial autophagy. In cardiovascular diseases, it alleviates ischemia-reperfusion injury by regulating cardiomyocyte autophagy and apoptosis, demonstrating its broad regulatory role across various pathological conditions. Genetic studies further underscore the clinical significance of ATG12. Polymorphisms in the ATG12 gene (e.g., rs26537 and rs26538) have been significantly associated with the risk of head and neck squamous cell carcinoma, hepatocellular carcinoma, and atrophic gastritis. Notably, the risk allele of rs26537 enhances ATG12 promoter activity, leading to its overexpression and promoting tumorigenesis. These findings provide a molecular basis for individualized risk assessment and targeted interventions based on ATG12 genotype. Despite significant progress, many aspects of ATG12 biology remain unclear. The precise regulatory mechanisms of its post-translational modifications (e.g., ubiquitination and acetylation) are yet to be fully elucidated. Additionally, the molecular pathways underlying its non-canonical functions, such as metabolic regulation and immune modulation, require further investigation. Moreover, the functional heterogeneity of ATG12 in different tumor microenvironments and its role in drug resistance warrant in-depth exploration. Future research should integrate advanced technologies such as cryo-electron microscopy, single-cell sequencing, and organoid models to decipher the intricate regulatory network of ATG12. Additionally, developing small-molecule inhibitors or gene-editing tools targeting its protein interaction interfaces (e.g., the ATG12-ATG3 binding domain) may help overcome current therapeutic challenges. Through interdisciplinary collaboration and clinical translation, ATG12 holds promise as a next-generation molecular target for precision intervention in autophagy-related diseases. This review summarizes the structure and function of ATG12, its role in autophagy initiation, its physiological functions, and its involvement in disease pathogenesis. Furthermore, it discusses future research directions and potential challenges, emphasizing ATG12’s potential as a biomarker and therapeutic target in autophagy-related diseases.

ObjectiveTo investigate the contamination status, transmission risk and drug resistance of Klebsiella pneumoniae (KP) on the object surfaces in the surrounding environment of hospitalized patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) , so as to provide a scientific guidance for the prevention and control of healthcare-associated infection. MethodsSamples from the surfaces of objects in the surrounding environment of CRKP infected patients living in the intensive care unit (ICU) and hand specimens from healthcare workers were collected for KP isolation and identification, as well as drug susceptible test in a medical institution located in Minhang District, Shanghai from 2021 to 2023. Additionally, both univariate and multivariate logistic regression analyses were used to identify the influencing factors associated with KP contamination in the hospital environment. ResultsA total of 546 surface samples were collected from the surrounding environment objects of 15 patients infected with CRKP, with a KP detection rate of 6.59% (36/546).The KP detection rate in the ICU of general ward (10.22%) was higher than that in the ICU of emergency department (2.94%) (χ²=12.142, P<0.001). Moreover, the KP detection rate on the surfaces of patient-contacted items (15.66%) was higher than that on shared-use items (6.25%), cleaning items (10.00%), and medical supplies (3.30%) (χ²=17.943, P<0.001). Besides, the detection rate of KP in items sent out of hospital for disinfection (15.38%) was higher than that in those self-disinfected (4.20%) (χ²=19.996, P<0.001).The highest detection rate of KP was observed in high-temperature washing (15.13%, 18/119) (χ²=21.219, P<0.001), while the lowest detection rate was observed in antibacterial hand sanitizer with trichlorohydroxydiphenyl ether sanitizing factor (0, 0/60) ( χ²=21.219, P<0.001).The detection rate of KP in samples taken more than 24 hours after the last disinfection (23.08%) was higher than that in those taken at 4 to24 hours (12.90%) and less than 4 hours (4.22%) (χ²=23.398,P<0.001).ICU of general ward (OR=4.045, 95%CI: 2.206‒7.416), patient-contacted items (OR=3.113, 95%CI: 1.191‒8.141), and self-disinfection ( OR=0.241, 95%CI:0.144‒0.402) were influencing factors for KP contamination in environmental surface. From 2021 to 2023, the drug resistance rates of hospital environmental KP isolates showed an upward trend (P<0.001) to antibiotics such as ceftazidime and gentamicin. Furthermore, high drug resistance rates of KP (>90%) were observed to ciprofloxacin, levofloxacin, cefotaxime, ceftriaxone, and cefepime. ConclusionCRKP can be transmitted outward through the surfaces of objects in the patients’ surroundings, and the drug resistance situation is severe. In clinical settings, it is necessary to implement isolation measures for CRKP infection patients, to increase the frequency of disinfection for objects in their surroundings, to strengthen hand hygiene practices, and to use antibiotics appropriately.

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Background::Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods::This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results::A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. Conclusion::The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.

Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P＜0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P＜0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P＜0.05).There was no significant difference in elbow tenderness between two groups at each time point(P＞0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.

Objective To compare the efficacy of arthroscopic rotator cuff repair using single row,double row,and suture bridge techniques in treating rotator cuff injuries and analyze the influencing factors of postoperative chronic pain.Methods Clinical data of 106 patients with rotator cuff injury to receive arthroscopic rotator cuff repair from January 2021 to February 2023 were retrospectively collected,were divided into single row group(n=35),double row(n=32)and suture bridge group(n=39).All patients from the three groups were evaluated using the pain visual analogue scale(VAS)and the Constant-Murley shoulder score(CMS)before surgery and 3,6,and 12 months after surgery,and their external rotation and forward flexion range of motion were measured.The incidence of postoperative retearing and chronic pain after surgery were compared among the three groups.Patients were divided into chronic pain group(n=21)and non-chronic pain group(n=85)depending whether chronic pain was seen or not after surgery and the clinical data was compared.Risk factors for postoperative chronic pain in arthroscopic rotator cuff repair patients were assessed via binary Logistic regression analysis.Results The VAS in suture bridge group was significant lower than that in single row group and double row group at 3,6 months after surgery,the VAS at 3,6,12 months after surgery in three groups were lower than that before surgery,the differences were statistically significant(P<0.05).The CMS score in suture bridge group was significant higher than that in single row group,double row group at 3,6 months after surgery,and all groups at 3,6,12 months after surgery were higher than that before surgery.The external rotation range of motion,and forward bending range of motion in suture bridge group were larger than those in single row group,double row group at 3,6 months after surgery,and all groups at 3,6,12 months after surgery were larger than those before surgery,the differences was statistically significant(P<0.05).The incidence of postoperative retearing in suture bridge group was significant lower than that in single row group and double row group,the difference was statistically significant(P<0.0167),but there was no difference between single row group and double row group(P>0.0167).The chronic pain occurrence was no statistical difference among the three groups(P>0.05).The chronic pain group had higher proportions of women,tear diameter<1.0 cm,and severe postoperative pain than those of non-chronic pain group(P<0.05).Other clinical data[age,body mass index(BMI),course of disease,location of injury,cause of injury,smoking and drinking history]were comparable between the two groups,the differences were not statistically significant(P>0.05).According to binary Logistic regression analysis,after adjusting for confounding factors(age,BMI,disease course,location and cause of injury),female gender,tear diameter<1.0 cm,and severe postoperative pain were independent risk factors for chronic pain after arthroscopic rotator cuff repair surgery(P<0.05).Conclusion In treating patients with rotator cuff injury,arthroscopic suture bridge outperforms single row and double row techniques in alleviating shoulder joint pain,promoting functional recovery and increasing range of motion,and presents lower risk of retearing.However,all three have some risk of chronic pain after surgery.Female gender,tear diameter<1.0 cm,and severe postoperative pain are independent risk factors for postoperative chronic pain.

Objective:To evaluate the extracorporeal membrane oxygenation (ECMO) related outcomes during hospitalization during the intensive care unit (ICU) in idiopathic pulmonary fibrosis (IPF) patients with high body mass index (BMI, >25 kg/m 2) undergoing lung transplantation with ECMO support. Methods:A retrospective observational study was conducted. IPF patients who received ECMO during lung transplantation admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from 2019 to 2020 were enrolled. Preoperative indicators including, demographics, comorbidities, arterial blood gas, and laboratory indicators; intraoperative indicators, such as lung lobe volume reduction, surgical type, surgical time, cold ischemia time, blood loss and transfusion volume; immediate indicators upon admission to the ICU, such as blood gas analysis and laboratory indicators; ECMO related outcomes, such as ECMO mode, ECMO support time, ECMO related complications (bleeding at the catheterization site, intraductal thrombosis, lower limb ischemia), and the length of ICU stay, duration of mechanical ventilation, and 30-day survival rate were collected. According to BMI, patients were divided into three groups: light weight group (BMI < 18.5 kg/m 2), normal weight group (BMI 18.5-24.9 kg/m 2), and overweight group (BMI ≥ 25.0 kg/m 2). Mainly to compare the relevant outcomes of ECMO among patients during ICU. Results:A total of 114 IPF patients who received ECMO support during lung transplantation were collected, including 23 cases in the light weight group, 63 cases in the normal weight group, and 28 cases in the overweight group. Compared with patients with underweight and normal weight, overweight patients were more likely to have hypertension (46.4% vs. 8.7%, 23.8%, P < 0.01) and coronary heart disease (32.1% vs. 4.3%, 20.6%, P < 0.05) before surgery, which was consistent with international guidelines for obesity. Other clinical data (preoperative, intraoperative, ICU characteristics) showed no statistically significant differences and were comparable. There was no statistically significant difference in terms of ECMO related outcomes, such as ECMO related complications [veno-venous (V-V) mode: 78.3%, 77.8%, 78.6%, veno-arterial (V-A) mode: 21.7%, 22.2%, 21.4%], ECMO support time (hours: 61.70±20.03, 44.57±5.76, 41.77±7.26), ECMO related complications (bleeding at the catheterization site: 4.3%, 7.9%, 14.3%; intraductal thrombosis: 8.7%, 12.7%, 17.9%; lower limb ischemia: 8.7%, 12.7%, 14.3%), and the length of ICU stay (days: 11±3, 7±1, 9±1), duration of mechanical ventilation [days: 2 (2, 11), 2 (2, 6), 3 (2, 8)] among the light weight group, normal weight group, and overweight group (all P > 0.05). Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 30-day cumulative survival rate among the three groups (Log-Rank test: χ2 = 0.919, P = 0.632). Conclusions:High BMI does not worsen ECMO-related outcomes or adversely affect early prognosis in IPF patients undergoing lung transplantation. BMI as a single parameter should not be a contraindication for the use of ECMO in lung transplantation surgery for IPF patients.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective To investigate the mental resilience of disabled elderly with suicidal ideation in nursing homes and analyze its related factors.Methods By using convenience sampling and the Chinese version of the Beck scale for suicide ideation,a total of 119 disabled elderly with suicidal ideation were screened from 8 nursing homes in Chongqing from May to October 2022.Then they were investigated with the general information questionnaire,the Memorial University of Newfoundland scale of happiness,the 10-item connor-davidson resilience scale and the hospital depression scale.Results The average score of resilience of disabled elderly with suicidal ideation was(1.58±0.70)points,which was at a lower level.There were statistically significant differences in the mental resilience of disabled elderly with suicidal ideation in terms of the nature of the nursing homes,the degree of disability and education,the length of stay,the frequency of communication with relatives and participation in collective activities.The mental resilience of disabled elderly with suicidal ideation was negatively correlated with depressive symptoms(r1=-0.631,P＜0.001),and positively correlated with subjective well-being(r2=0.652,P＜0.001).Among disabled elderly with suicidal ideation,the degree of education and subjective well-being positively predicted mental resilience,while depressive symptoms negatively predicted mental resilience(adjusted R2=0.521,P＜O.001).Conclusion The mental resilience level of disabled elderly with suicidal ideation in nursing homes is lower.Nursing homes should focus on improving the mental resilience of disabled elderly with lower educational level,lower subjective well-being and higher depression symptoms,so as to improve their adaptability.