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.

The treatment of war wounds is the core content of military medicine. Considering the development of weapons, the change of war mode and the need of health services, the treatment of war wounds must be adapted to the requirements of the new situation. Wounds in modern wars are the traumas caused in all-domain hybrid warfare. Through local wars and related military operations, foreign armed forces especially the US armed forces have implemented or improved many technologies and health service countermeasures for the treatment of war wounds, and put forward new concepts and strategies for war wound treatment, which may serve as a valuable reference in the establishment of Chinese combat casualty care system in the conditions of future warfare and a combat casualty care system that fits the Chinese characteristics. For this purpose, the author introduced the new concept and strategy of wound treatment in modern wars from two aspects of the overall health and self-rescue and mutual rescue training, extension of the rescue force and application of new technologies in combat casualty care, hoping to provide a reference for the establishment of a combat casualty care system with Chinese characteristics in the conditions of future warfare.

Objective To investigate the clinical characteristics,treatment and prognosis of tuberculosis in patients with autoimmune diseases after tumor necrosis factor-αinhibitors.Methods Clinical data of 33 patients with TB after biologics(tumor necrosis factor-α inhibitors)treated in Guangzhou Chest Hospital from January 2019 to March 2023 were collected,including 25 males and 8 females,with a median age of 32 years.The clinical symptoms,laboratory results,imaging and tracheoscopic features,pathological features,treatment and outcome were analyzed retrospectively.Results The common clinical manifestations were cough(26/33),sputum(23/33)and fever(17/33).The most common cases were pulmonary tuberculosis(32/33),bronchial tuberculosis(15/33),mediastinum and hilar lymph node tuberculosis(11/33).Bilateral lung spread of tuberculosis(21/33),intrapulmonary spread of tuberculosis(bronchus,mediastinal hilar lymph nodes,pleura)(19/33),extrapulmonary tuberculosis(18/33),pulmonary tuberculosis with intrapulmonary or extrapulmonary tuberculosis(26/33).Blood CD4+T lymphocyte test was normal(23/33),and blood IGRA test was positive(27/33).Pulmonary imaging miliary nodules(8/33).The histopathology of the lymph nodes showed atypical granulomatous nodules.The duration of anti-tuberculosis treatment is 8-32 months.1 case of death.Conclusion Patients with autoimmune diseases complicated with tuberculosis after the application of tumor necrosis fact-α inhibitor are more likely to have double lung lesions,which are easy to spread to lung tissues and multiple organs of the body,and have decreased immune function.Most of them need to extend the treatment course,and the prognosis is generally good after comprehensive treatment.

Objective To preliminarily investigate the association between changes in intestinal microbiota and oral microbiota of allogeneic hematopoietic stem cell transplantation(allo-HSCT)patients and early gastrointestinal acute graft versus host disease(aGVHD),and try to explore potentially effective biomarkers and provide theoretical basis for early prediction and intervention of gastrointestinal aGVHD.Methods Ten acute leukemia patients who developed gastrointestinal aGVHD within 1 month after receiving allo-HSCT in Department of Hematology of Sichuan Provincial People's Hospital from September 2021 to June 2023 were enrolled,and their fecal samples and saliva samples before and after the aGVHD were collected.16S rRNA sequencing analysis was applied for the differential changes in intestinal and oral microbiota before and after the development of early gastrointestinal aGVHD.Results ① A decrease in Bacteroides spp.and an increase in Enterococcus spp.and Enterobacteriaceae spp.in the intestinal microbiota were positively correlated with the occurrence of early upper gastrointestinal aGVHD(P＜0.05),whereas no significant difference was observed in the overall microbial diversity of the oral microbiota(P＞0.05).② LEfSe analysis of the intestinal microbiota before and after gastrointestinal aGVHD revealed an increase in Klebsiella spp.and Enterococcus spp.and a decrease in Escherichia coli;In the oral microbiota,LEfSe analysis revealed 10 microbial markers with significant difference,of which Gamma proteobacteria was the most significant.③ The difference in β-diversity of the intestinal microbiota was significant(P=0.03),whereas there was no significant difference in the α-and β-diversity of the oral microbiota.Conclusion Significant differences are found in intestinal microbiota before and after the occurrence of early gastrointestinal aGVHD in patients after Allo-HSCT,and the occurrence may have a correlation with the chang in oral microbiota.

Objective:To explore high-risk sexual behaviors of HIV/AIDS and related factors in young students in Guangzhou.Methods:A cross-sectional survey was conducted in 5 different types of Guangzhou colleges by convenience sampling with minimum number of classes per grade and 600 samples per school from September to November 2021. The R 4.2.2 software was used to consolidate databases. Simultaneously, a logistic regression model and a decision tree algorithm model, stratifying by whether sexual behaviors had occurred before, were constructed. In each layer, the prediction performance of the two models was evaluated through area under receiver operating characteristic and the confusion matrix, and then the model with high prediction performance was retained.Results:A total of 7 346 students were surveyed. The proportion of the respondents reporting sexual experience were 9.08% (667/7 346), in whom 26.24% (175/667) had risky sexual activity in the past year. The decision tree algorithm model performs well in predicting whether high-risk sexual behaviors have occurred in the past year. When the complexity parameter value is 0.018, and nsplit reaches 4, which means there are 5 leaf nodes in the model, the cross error of the tree will be the smallest. The first best grouping variable in the decision tree was whether to use condoms throughout the first sexual behavior. If condoms were used at their sexual debut, but homosexual practices have occurred in the past year, the probability of risky sexual behavior will increase. If homosexual practices have not occurred in the past year, but the age of sexual debut was below 18 years old while the period of HIV education was after high school, the probability of risk sexual behavior will also increase.Conclusions:AIDS-related risky behaviors of young students still deserved attention. The experience of sexual debut and whether AIDS-related health education has been received before the sexual debut were significant predictors for the occurrence of high-risk sexual behavior. The decision tree algorithm model has particular applicability for predicting and screening potential risk populations.

The construction of wound repair discipline system with Chinese characteristics is a process of continuous optimization and improvement. Due to the different conditions and the situations that vary widely from region to region and from hospital to hospital, various forms of wound repair specialty or consortium will exist within a period of time and to a extent plays a key role in promoting the construction of the wound repair discipline system with Chinese characteristics. This article introduced several kinds of construction modes of wound repair specialty or regional alliance of wound repair specialty in recent years. Their successful experience is worth learning and drawing lessons from.

Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Cisplatin/metabolism* ; Esophageal Neoplasms/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Growth Differentiation Factor 15/therapeutic use* ; Receptor, Transforming Growth Factor-beta Type II/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

China has experienced three-year anti-epidemic struggle against coronavirus disease 2019 (COVID-19) epidemic and obtained fruitful achievements in the construction of rescue system for major infectious disease. Treatment of severe mass trauma is a major national need. How to learn from the successful experiences of the construction of this rescue system for major infectious disease is a question worth considering. The author rethink s on how to further promote the construction of the traumatology discipline system with Chinese characteristics from six aspects, ie, the construction of the traumatology discipline system as a national strategy, the connotation of the trauma treatment system with Chinese characteristics, the role of the self-characteristics of traumatology in the trauma treatment chain, the new breakthrough in the basic theory and key technology of trauma treatment, the construction of innovative talents in traumatology to a new level as well as public training and education and the legislation strengthening.