ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs'effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.We compared outcomes and side effects between patients with and without prior TB.Of 116 patients(40 with TB history,76 without),prior TB didn't reduce treatment effectiveness but did increase severe side effects.Notably,older patients(≥65 years)faced a higher risk of severe side effects.Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs,stressing the need for careful monitoring and personalized care.

Objective:To investigate the alteration in iodine nutritional status and influence on thyroid function in the elderly aged≥65 years following water source modification in high iodine areas.Methods:Data from Yaoji Town, Xuzhou, Jiangsu(an area with high iodine due to water sources) of the national epidemiological survey on thyroid diseases, iodine nutrition, and diabetes(TIDE study) in 31 provinces and cities in China from 2015 to 2017 were utilized. Additionally, data from the screening, monitoring, and intervention on thyroid diseases(TOPS study) in the elderly(≥65 years) in Shunhe Town, Suqian, Jiangsu(an area with iodine levels exceeding the recommended amount), and Yaoji Town, Xuzhou from May to August 2021, are included. Each subject completed a questionnaire, physical examination, laboratory tests and thyroid ultrasound examinations. A total of 2 717 subjects aged≥65 years were included, including group 1, 258 subjects in TIDE study; Group 2, 1 313 subjects in TOPS Xuzhou area; Group 3, 1 146 subjects in TOPS Suqian area.Results:The urinary iodine concentration(UIC) in group 2 was significantly lower than that in group 1 [(235.16±67.09)μg/L vs (491.58±384.93)μg/L, P<0.001], but no significant difference compared with group 3 [(235.16±67.09) μg/L vs(231.62±66.11) μg/L, P>0.05]. The serum TSH level in group 2 was significantly lower than that in group 1 [(2.92±5.14)μIU/mL vs (4.15±9.19)μIU/mL, P<0.001]. Compared with group 2 and 3, the prevalence of subclinical hypothyroidism in the elderly in group 1 was the highest(22.48% vs 10.13% and 8.12%, P<0.001). TSH levels were linearly correlated with age in both excessive iodine and more than adequate iodine nutrition areas. TSH level was gradually increased with age. Conclusion:The alteration in TSH levels among the elderly is notably linked to both aging and iodine status. The prevalence of hypothyroidism in the elderly can be significantly reduced when the iodine nutrition status of the elderly returns to normal.

Specific pathogen-free(SPF)chickens are widely used in the research of avian diseases and vaccines.Vertically transmissible diseases are transmitted to chickens through vertical transmission,seriously affecting their survival rate,increasing production costs,and causing significant economic losses to the poultry industry,while severely impacting the breeding and use of SPF chickens.Therefore,it is crucial for researchers and managers to enhance their understanding of vertically transmissible pathogens in chickens and to develop effective monitoring measures.Quality monitoring is an important part of ensuring the quality of SPF chickens,with pathogen detection being the primary step.Based on this,it is necessary to cultivate qualified SPF chickens through purification methods and biosecurity measures.This paper reviews the major vertically transmissible pathogens in chickens,including viral pathogens,bacterial pathogens and mycoplasmas,as well as their detection methods.This study compares the differences in microbiological testing items and methods for SPF chickens between the U.S.corporate standard and the Chinese national standard.Analysis of the results shows that in both standards,vertically transmissible pathogens such as Escherichia coli,Proteus mirabilis,Salmonella,and avian leukosis are not included in the microbiological testing items for SPF chickens.Instead,these pathogens are characterized by mixed infections,and outbreaks can seriously affect flock health.To produce higher-quality SPF chickens,it is necessary to include these pathogens in the mandatory testing items.The aim of this paper is to help readers understand the relevant standards for microbiological monitoring of SPF chickens,the hazards of vertically transmissible pathogens,and prevention and control strategies,so as to provide a reference for the detection and purification of pathogens in SPF chickens.

In recent years,with the gradual maturity of achievable remote collection of digital health technology,more and more clinical research have applied this technology to improve the quality of data collection and reduce the burden on subjects.However,its technological characteristics of detachment from the diagnostic and treatment environment and real-time transmission of sensitive information also pose corresponding risks to the protection of subjects'rights and interests and data standardization management,among which personal information protection and data control permissions are more prominent issues.Based on risk analysis and regulatory review,this paper explored the responsibilities of multiple parties,including the sponsors,researchers,clinical trial institutions,and ethics committee,as well as proposed five elements of special concern for ethical review,with a view to providing a reference for promoting the standardized development of digital health technology in clinical research.

Objective To analyze the epidemiological characteristics of leptospirosis in China from 2010 to 2022, so as to provide insights into formulation of the leptospirosis control strategy. Methods All data pertaining to clinically diagnosed cases and confirmed cases of leptospirosis reported in China from January 1, 2010 to December 31, 2022 was collected from Chinese Disease Prevention and Control Information Management System. The spatial, temporal and population distributions, and report and diagnosis institutions of leptospirosis cases were analyzed using a descriptive epidemiological method. Results A total of 4 559 leptospirosis cases were reported in China from 2010 to 2022, with an annual average number of 351 cases, and the number of reported leptospirosis cases reduced from 679 cases in 2010 to 158 cases in 2018. A total of 4 276 leptospirosis cases were reported in Sichuan Province, Yunnan Province, Guangdong Province, Hunan Province, Fujian Province, Zhejiang Province, Guangxi Zhuang Autonomous Region, Anhui Province, Jiangxi Province and Guizhou Province, accounting for 93.79% of the total number of leptospirosis cases in China. The number of leptospirosis cases had recently appeared a remarkable decline in Yunnan Province, while a significant rise was seen in the number of leptospirosis cases in two provinces of Zhejiang and Guangdong. No leptospirosis cases were reported in Henan Province from 2010 to 2020; however, there were 5 cases and 2 cases reported in 2021 and 2022, respectively. There was only one leptospirosis case reported in Shaanxi Province from 2010 to 2017; however, leptospirosis cases were reported in the province for 5 consecutive years since 2018. Leptospirosis cases were reported throughout the year in China from 2010 to 2022, with the peak of incidence found during the period between August and October, and the peak of leptospirosis incidence varied in provinces. A higher number of leptospirosis cases was seen among men than among women, with a male to female ratio of 2.3:1, and the median age of leptospirosis cases was 50 years (interquartile range, 23 years), with the highest proportion of leptospirosis cases reported at ages of 51 to 60 years (23.21%). Among all reported leptospirosis cases, 53.28% were confirmed cases, and the proportion of confirmed cases increased from 35.05% in 2010 to 61.66% in 2022. In addition, there were 67.22% of leptospirosis cases (2 937 cases) reported by comprehensive hospitals, 20.44% (893 cases) by disease control and prevention institutions, 7.23% (316 cases) by grassroots healthcare institutions and 5.10% (223 cases) by other healthcare and medical institutions, and the mortality of reported leptospirosis cases was 1.07% in China from 2010 to 2022, with a higher mortality seen among men than among women (1.39% vs. 0.36%; χ² = 9.52, P = 0.002). Conclusions The incidence of leptospirosis remained at a low level in China from 2010 to 2022, and southern China was still the main endemic area for leptospirosis. The epidemiological characteristics of leptospirosis cases varied in endemic provinces, and leptospirosis cases had been continued to be reported in Shaanxi and Henan provinces, which should be paid much attention to. Intensified surveillance of leptospirosis, improved diagnosis and treatment capability of leptospirosis cases and leptospirosis control with adaptations to local circumstance are recommended.

Objective To systematically evaluate qualitative studies on the experience of transition from adolescent to adult medical care for patients with congenital heart disease(CHD),and to provide a reference for exploring CHD transition management options and developing intervention strategies.Methods A computerized search of PubMed,Embase,Web of Science,Cochrane Library,EBSCO,CINAHL,China Knowledge Network,Wanfang database,Vipshop database,and China Biomedical Literature Database for qualitative studies on the transition experience of CHD patients from adolescence to adult medical care was conducted for the period from the establishment of the database to April 2023.The quality of the literature was evaluated using the Joanna Briggs Institute(JBI)Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016),and the results were integrated using meta-integration methods.Results A total of 9 studies were included,and 49 research results were extracted,and 11 categories were summarized.The final synthesis included 4 integrated results:①Complex attitudes towards healthcare transition,with both attachment and expectation:attachment to paediatric healthcare providers,expectation of transition to adult healthcare providers.(2)Facing multiple healthcare transition challenges:lack of adequate preparation for healthcare transition,parents withdrawing from the role of disease manager,large differences in services between paediatric and adult healthcare providers.③Expect to receive multiple supports:expect to receive comprehensive health education from healthcare personnel,expect healthcare institutions to set up healthcare transition counselling clinics and achieve handover of illness,expect to receive companionship and support from parents,expect to receive understanding and help from peers.④ Per-ceived benefits of medical transition:increased ability to manage illness,role change and personal growth.Conclusion Adolescents with CHD have a complex experience of transitioning to adult healthcare,and healthcare professionals should be attentive to their feelings,encourage them to deal with challenges positively,and provide adequate information and joint parental and peer support to facilitate a smooth transition to adult healthcare for adolescents.

Objective To evaluate and integrate the facilitators and barriers to adherence to diet or exercise interventions in patients with overweight or obesity.Methods PubMed,Web of Science,Embase,CINAHL,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and VIP Chinese Biomedical Literature Database were searched by computer from the establishment of the database to October 14,2023.The 2016 edition of the Joanna Briggs Institute(JBI)evidence-based health care center qualitative research evaluation criteria was used to evaluate and integrate the included literature.Results A total of 19 studies were included,and 38 outcomes were distilled into 12 categories,and the results were consolidated into facilitators(disease threat perception,self-body perception,self-adjustment,sense of responsibility,social support)and barriers to intervention adherence(poor treatment benefit,low self-efficacy,lack of knowledge,competitive priorities,extemal environmental constraints,economic conditions,poor intervention design).Conclusion There are many facilitators and barriers of diet or exercise intervention perceived by patients.It is suggested that follow-up intervention research should be used as a reference to improve the treatment compliance of patients.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.