Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective: To understand anxiety symptoms among medical college students and their relationship with social ecological risk factors, so as to provide reference for mental health promotion among medical students. Methods: From September to October 2021, a convenient cluster sampling method was used to include 1 274 freshmen to senior students of a medical school in Taiyuan City, and the Generalized Anxiety Disorder-7 and adolescent social ecological risk factors assessment questionnaire were used. Multivariate binary Logistic regression was used to analyze the association between anxiety symptoms and social ecological risk factors among medical students. Results: The overall detection rate of anxiety symptoms among medical students was 16.2%. The rate of anxiety varied significantly by grade (freshman: 19.9%, sophomore: 13.0%, junior: 14.0%, senior: 18.9% ) and number of friends (≤2: 22.8%, 3-5: 14.4%, ≥6: 11.8%) ( χ 2=8.70, 16.34, P <0.05). Spearman correlation analysis showed that individual, family, school, community, policy, culture, time, and total score in socio ecological risk factors were positively associated with anxiety symptom scores at different levels of risk ( r=0.33, 0.25, 0.32, 0.16, 0.15, 0.16, 0.16, 0.35, P <0.01). Logistic regression analysis showed that high risk for personal dimension of the socio ecological risk factors was positively associated with rate of anxiety symptoms among medical students ( OR=3.32, 95%CI =1.66-6.61), and remained positively associated ( OR=2.98, 95%CI =1.49-5.94) after adjusting for grade and number of friends ( P <0.01). Conclusions Exposure to high personal dimensions of socio ecological risk factors increases the risk of developing anxiety symptoms among medical students. A focus should be placed on the personal factors associated with anxiety to promote medical students mental health.

Objective To systematically retrieve,evaluate and integrate the best evidences on the early fluid resuscitation management in the patients with acute pancreatitis(AP)at home and abroad to provide ref-erence for clinical decision.Methods The related evidences on the early fluid resuscitation management in the AP patients were retrieved by computer from the databases of BMJ Best Practice,Up To Date,JBI,National Institute for Health and Care Excellence,Registered Nurses Association of Ontario,Guideline International Network,Scottish Intercollegiate Guidelines Network,International Association of Pancreatology,American Pancreatic Association,American College of Gastroenterology,Yimaitong,Cochrane Library,PubMed,Em-bass,CINAHL,The Web of Science,CNKI,Wanfang databases.The retrieval time limit was from the data-base establishment to March 20,2022.The literatures types included thematic evidence summarization,guide-lines,evidence summaries,systematic reviews and expert consensus.The researchers conducted the literature quality evaluation.The literatures meeting the standard conducted the evidence extraction.Results A total of 13 arti-cles were included,including 3 special subject evidence summary,4 guidelines,2 evidence summary,2 systematic evalu-ation and 2 expert consensus.A total of 16 pieces of best evidence were integrated,involving 4 aspects of organization management,evaluation and monitoring,fluid infusion strategy and health education.Conclusion It is recommended to use the target-oriented therapy for early fluid resuscitation management,and perform the fluid resuscitation immediate-ly after diagnosis,according to the patient's underlying disease,disease changes and monitoring indicators,implement precise early fluid resuscitation in order to reverse pancreatic microcirculation disorder,increase tissue perfusion and improve the patient's prognosis.

Objective:Retinal vein occlusion(RVO)is the second most common retinal vascular disease worldwide,and the retinal perfusion status is closely related to the prognosis of the disease.Macular perfusion status is particularly correlated with visual acuity.This study aims to investigate the changes in macular perfusion indicators in RVO using optical coherence tomography angiography(OCTA)and analyze the correlation between macular perfusion status and visual acuity. Methods:This cross-sectional study included 41 RVO patients,who were divided into 2 groups based on the occlusion site:18 cases in the central retinal vein occlusion(CRVO)group and 23 cases in the branch retinal vein occlusion(BRVO)group.Additionally,they were categorized into ischemic RVO(23 cases)and non-ischemic RVO(16 cases)groups based on the presence of ischemia(2 eyes were excluded due to hemorrhage obscuring the peripheral retina,making it impossible to confirm the area of non-perfusion).A control group of 29 healthy individuals matched by sex and age was also recruited.Macular perfusion indicators were measured using OCTA,and the correlation between macular perfusion status and visual acuity was analyzed. Results:Compared with healthy eyes,RVO eyes showed an increased foveal avascular zone(FAZ)area and significantly reduced superficial and deep vessel density(P＜0.001).However,there were no significant differences in central foveal thickness(CFT)or macular perfusion indicators between the CRVO and BRVO groups(P＞0.05).The best corrected visual acuity(BCVA)at the logarithm of the minimum angle of resolution(logMAR BCVA)was significantly negatively correlated with both superficial and deep retinal vessel density in RVO eyes(unstandardized coefficient B=-0.039,B=-0.042;P=0.017,P=0.040).The average BCVA in the ischemic RVO group was significantly worse than that in the non-ischemic RVO group(0.82±0.44 vs 0.45±0.29,P=0.007).The ischemic RVO group also had a larger FAZ area(P=0.003)and lower superficial and deep retinal vessel density(P＜0.001,P=0.008,respectively)compared with the non-ischemic RVO group.The severity of macular ischemia did not correspond directly with the peripheral ischemia severity in RVO. Conclusion:Macular perfusion status is significantly reduced in RVO eyes compared to healthy eyes,which negatively impacts and limits visual acuity in RVO patients.Eyes with ischemic RVO have poorer visual acuity and macular perfusion status than those with non-ischemic RVO.OCTA is advantageous for observing vascular morphology and quantifying macular perfusion status,making it an effective tool for assessing disease progression.

This article mainly elaborated the acupuncture and moxibustion treatment scheme of"eighteen needles for reproduction"based on Professor You Zhaoling's reproductive axis theory of"heart-kidney-Chong Ren-uterus".The"eighteen needles for reproduction"aims to regulate the disordered reproductive axis in gynecological reproductive diseases.It selects the acupoints on the main viscera and meridians of the reproductive axis as the main acupoints,and the acupoints regulating the qi and blood of the related viscera as the matching acupoints.Through specific manipulation,it can regulate the qi and blood,dredge the meridians,and treat the viscera,so as to nourish the essence and help pregnancy,and provide ideas and reference for the treatment of gynecological reproductive diseases with acupuncture and moxibustion.

Spinal muscular atrophy(SMA)is a rare genetic neuromuscular disease characterized by significant clinical heterogeneity among patients.According to the severity and progression rate of the condition,the disease is classified into five types.In recent years,because of the promotion of multidisciplinary manage-ment and the application of disease-modifying therapies,the prognosis of SMA patients has significantly im-proved,resulting in more patients entering into the stage of adolescence and adulthood.The varying conditions of different types of patients in the adolescence and adulthood make the manifestations more complex and diverse,leading to the difficulty in identification and diagnosis.Because of the vast territory and large popula-tion in China,coupled with uneven health care development among different regions of the country,the diagno-sis and treatment for adolescent and adult SMA patients are very challenging.Misdiagnosis or delayed diagnosis remains a primary unresolved issue for many patients.The fact that patients have to visit various departments in their initial consultation highlights the importance of enhancing the recognition of high-risk adolescent and adult SMA populations among the non-neuromuscular specialists.This article attempts to explore a simple,clear,and highly operational"portrait"way of identifying the high-risk adolescent and adult SMA patients in the popula-tion,aiming at assisting the non-neuromuscular specialists to diagnose SMA patients in a way of early recogni-tion and diagnosis and to ensure patients receiving standardized treatment as early as possible.The ultimate goal is for the higher clinical gain and a better life for patients and their families.