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: 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.

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.

Objective:To explore the clinical characteristics and genetic variant of a patient with desminopathy manifesting with atypical symptoms.Methods:A patient who was admitted to the Department of Neurology of Jing′an District Central Hospital on February 24, 2021 was selected as the study subject. Clinical data, laboratory tests, muscle pathology, muscle magnetic resonance imaging (MRI) and genetic testing of the patient were retrospectively analyzed.Results:The patient had developed myalgia after lower limb activity, and gradually developed asymmetrical muscle weakness and atrophy of the lower limbs. Cardiac examination revealed atrioventricular block and decreased left ventricular diastolic function. Muscle MRI showed that semitendinosus, sartorius, gracilis, fibula, gastronemius and supinator muscles were selectively involved at the early stage. Muscle biopsy confirmed pathological changes of desmin positive myofibrils. Genetic testing revealed that the patient has harbored a c. 1024A>G (p.n342d) missense variant in exon 6 of the DES gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS4_moderate+ PM2_supporting+ PP3_moderate+ PP1). Conclusion:Desmin disease has a great clinical heterogeneity. Postexercise myalgia of lower limbs is a rare clinical phenotype. For patients harboring the c. 1024A>G (p.n342d) variant of the DES gene, in addition to semitendinosus and fibula, Cardiac involvement is relatively insidious and easy to be ignored in clinic. Timely muscle MRI, muscle biopsy and gene detection will help the early diagnosis of the disease.

ObjectiveTo determine the antibody levels of varicella-zoster virus （VZV） in healthy individuals aged 1 to 30 years in Songjiang District of Shanghai， and to provide evidence for further development of varicella immunization strategies for healthy population. MethodsSix village committees were selected in Songjiang District through multi-stage stratified random sampling method from July to September 2022. Healthy individuals aged 1 to 30 years old in these villages were recruited and 3‒5 mL of venous blood was collected. Anti-VZV IgG antibody was tested by ELISA. Positive rate of anti-VZV IgG antibody and geometric mean concentration （GMC） were determined. ResultsA total of 315 healthy individuals aged （10.97±8.38） years were included in this study， of which 165 were males aged （11.00±8.52） years and 150 were females aged （10.96±8.25） years. Blood samples were collected and tested for anti-VZV IgG antibody， with the overall positive rate of 55.24% （174/315）. The GMC was calculated to be 99.73 mIU·mL^-1， with the GMC in those tested positive for anti-VZV IgG antibody of 413.11 mIU·mL^-1. The positive rate of anti-VZV IgG antibody and GMCs across age groups ranged between 13.33%‒86.67% and 16.36‒355.14 mIU·mL^-1， respectively. The highest GMC was found in the group of 20‒30 years old （355.14 mIU·mL^-1）， followed by 132.41 mIU·mL^-1 in the group of 5‒ years old and 138.12 mIU·mL^-1 in the group of 15‒ years old. Moreover， the positive rate was 38.47% in the group with 1-dose varicella vaccine and 63.49% in the group with 2 doses， while the GMC were 53.28 mIU·mL^-1 and 130.79 mIU·mL^-1 in these two groups， respectively. Multivariable analysis revealed that occupation was a risk factor associated with anti-VZV IgG antibody （OR=2.540）. Stratified analysis by varicella immunization history showed that among 2-dose vaccination group， time interval since the last dose was a protective factor （OR=0.315）. ConclusionsThe overall positive rate of anti-VZV IgG antibody in healthy population in Songjiang District of Shanghai remains low. The 2-dose varicella vaccination should be strengthened to improve the coverage in susceptible population.

【Objective】 To investigate the development of adaptability in children aged 2 - 6, and to explore its influencing factors, so as to provide reference for promoting the development of adaptability in young children. 【Methods】 Data were from the National Nutrition and Health Systematic Survey for Children in China, and 3 319 children aged 2 - 6 and their parents from 28 sites across 14 provinces were recruited in this study.The Development Scale for Children Aged 0 - 6 years (WS/T 580-2017) was used to measure the developmental quotient of children′s adaptive ability, and a survey questionnaire was used to collect relevant information about children and their parents. 【Results】 Among 3 319 children aged 2 - 6, the proportion of slightly low or low level of adaptability, moderate adaptability development, good and excellent adaptability development was 7.68%,66.25% and 26.06%, respectively.The proportion of children aged 5 - 6 with good and excellent adaptability was lower in 3-year-old and 4-year-old groups (χ²=59.29, P<0.05).Multiple stepwise linear regression showed that children′s gender (β=0.06), gestational age of birth (β=-0.05), only child (β=-0.04), left-behind child (β=-0.04), the main caregiver (β=-0.06), and the education level of parents (β=0.09, 0.10), whether parents actively pay attention to children′s emotions (β=-0.06) and whether children play with homemade toys (β=-0.04) were the influencing factors of children′s adaptive development quotient.Girls, full-term children, only children, non-left-behind children, children with parents as main caregivers, parents with a high level of education, parents who often take the initiative to pay attention to children′s emotions, and children who play with homemade toys had a higher level of adaptability development quotient. 【Conclusions】 The development level of adaptability in children aged 2 - 6 in China is mostly above the average level and is related to multiple factors.Targeted intervention work can be carried out on relevant factors in order to promote the development of children′s adaptability.

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.

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.