BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

The critical role of protein disequilibrium in driving carcinogenesis has long been recognized. Though several inhibitors of heat shock protein (HSP) family members have entered clinical trials, none of them have been approved for clinical use as a result of inevitable toxicity, leading to the identification of safer therapeutic approaches sharing a similar efficacy relevant and urgent. Through delineating the role of HSP90 inhibitors in arresting cancer hallmarks, this paper identified HSP90 inhibition as an effective therapeutic strategy capable of concomitantly targeting multiple key transformed properties of cancers via modulating cellular proteostasis. Through interrogating intrinsic connections between proteostasis and redox homeostasis, this paper proposed cold atmospheric plasma (CAP) as a possible alternative of HSP90 inhibitors with little adverse effects. This paper extended the therapeutic spectrum of HSP90 inhibitors and CAP to inflammation-driven pathologies including autoimmune diseases, as inflammation is a manifestation of failed proteostasis. These insights may conceptually advance our understandings on the driving force of cancers that can be easily extended to other disorders originated from imbalanced proteostasis and abnormal inflammation. Tools proposed here for inhibiting HSP90 including CAP and its possible synergy with HSP90 inhibitors may shift the current treatment paradigm to a new avenue in oncology and other relevant fields.

Objective:To explore the therapeutic law of moxibustion in Professor Zhou Meisheng's medical manuscripts for epidemic hemorrhagic fever (EHF) based on data mining and knowledge map technology.Methods:The manuscript data of Professor Zhou Meisheng's moxibustion treatment of EHFwere collected from Infectious Diseases Department of Dangshan County People's Hospital from December 16, 1985 to December 25, 1987. Graphpad Grism 8.0 software was used for descriptive analysis. PHP 5.4 program code was used for association rule analysis. SPSS Statistics 26.0 was used for clustering analysis. Neo4j Community 3.5.25 database was used to analyze the syndrome-weight graph.Results:205 prescriptions were included. There were 21 symptoms with frequency>40, in which the frequency of aversion to cold, fever, rash and irritability was 100%. The main types of moxibustion methods used in the treatment included moxibustion frame fumigation moxibustion, Wanying acupoint moxibustion pen moxibustion, and fire needle instead of moxibustion. There were 29 acupoints with a frequency of >25, including Zhongwan (CV12), Shenshu (BL23) and Mingmen (DU4), etc. Association rules showed that Sanyinjiao (SP6)-Zhongwan (CV12)-Feishu (BL13)-Shenshu (BL23)-Zhiyang (DU9) had the highest correlation. Six effective clustering combinations of moxibustion for EHF were summarized by clustering analysis. The weight graph can obtained the first 30 relationships with high correlation of target syndromes.Conclusions:Professor Zhou applied the idea of "moxibustion for heat syndrome" to the treatment of EHF, and took the method of "acupoint selection according to symptoms" as the main acupoint selection idea for moxibustion treatment of EHF. In clinical practice, moxibustion combined with auxiliary operation of TCM is often used to treat EHF, which can achieve good results.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To establish a diagnostic decision tree model for parotid tumors closely related to clinical treatment decisions based on multiparametric MRI and to explore and validate its clinical value in parotid tumor diagnosis.Methods:This study was a cross-sectional study that retrospectively collected MRI data from 461 patients with pathologically confirmed parotid tumors from June 2018 to December 2022 at the Ninth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, including 364 cases of benign tumors, 82 cases of malignant epithelial tumors, and 15 cases of lymphoma. Stratified random sampling was performed according to pathological results to divide the data into a training set (326 cases) and a validation set (135 cases). In the training set, there were 256 cases of benign tumors, 59 cases of malignant epithelial tumors, and 11 cases of lymphoma, while in the validation set, there were 108 cases of benign tumors, 23 cases of malignant epithelial tumors, and 4 cases of lymphoma. Based on MRI and clinical features, a decision tree model was established using the Chi-squared Automatic Interaction Detector (CHAID) algorithm, and the model was used for classification diagnosis. The diagnostic accuracy for benign tumors, malignant epithelial tumors, and lymphoma was calculated, and receiver operating characteristic curves were plotted to evaluate the diagnostic performance for each tumor type individually.Results:In the training set, four optimal diagnostic indicators for tumors were obtained through the CHAID algorithm, including tumor capsule, shape, apparent diffusion coefficient value, and time-signal curve type. A decision tree model was established based on these indicators. The overall diagnostic accuracy of the model for benign tumors, malignant epithelial tumors, and lymphoma was 90.8% (296/326) in the training set and 94.1% (127/135) in the validation set. The area under the curve for independent diagnosis of benign tumors, malignant epithelial tumors, and lymphoma in the training set was 0.964, 0.957, and 0.980, respectively, while in the validation set, it was 0.958, 0.944, and 0.992, respectively.Conclusion:The decision tree predictive model based on multi-parameter MRI demonstrates high efficacy in diagnosing benign tumors, malignant epithelial tumors, and lymphoma of the parotid gland.

Objective:To study the efficacy of endoscopic papillary balloon dilatation (EPBD) in the treatment of non-dilated small choledocholithiasis.Methods:Clinical data of 142 patients with non-dilated small choledocholithiasis admitted to Zhanjiang Central People's Hospital from April 2021 to March 2023 were retrospectively analyzed, including 63 males and 79 females, aged (55.1±15.4) years old. Patients were divided into the EPBD group ( n=63) and endoscopic sphincterotomy (EST) group ( n=79). Blood amylase, liver enzymology, liver metabolism, and blood routine were monitored before and 48 hours after treatment. The occurrences of intraoperative bleeding, perforation, post-ERCP pancreatitis (PEP), and cholangitis were compared between the groups. Patients were followed up and screened for stone recurrence by outpatient review 3 to 12 months from discharge. Results:Compared to preoperative data, the white blood cell count, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bili-rubin, and direct bilirubin decreased 48 hours after treatment (all P<0.05). The operation time in EPBD group was slightly longer than that in EST group [(43.1±5.9) min vs. (38.5±4.5) min, P=0.064] without statistical significance. There were no case of perforation in both groups. The incidences of intraopera-tive bleeding [3.17%(2/63) vs. 6.33%(5/79)], PEP [17.46%(11/63) vs. 10.53%(8/79)], and postoperative cholangitis [4.76%(3/63) vs. 1.27%(1/79)] were comparable between the groups (all P>0.05). Conclusion:EPBD could be feasible for non-dilated small choledocholithiasis, which does not increase the operation time and incidence of adverse events compared to EST.

ObjectiveTo explore the histological characteristics of the kidney in Mongolian gerbils of different ages. MethodsTen Mongolian gerbils of 2, 6, and 12 months old (half male and half female) were selected. After euthanasia, the kidneys were taken and paraffin sections were made. After HE, MASSON and PAS staining, the structural differences of different parts of the kidney tissue in gerbils of different ages were observed by digital scanning, and the relevant data of the kidney tissue were measured by image analysis software. ResultsThe number of proximal convoluted tubules was more than that of distal convoluted tubules in the renal cortex and outer medulla of gerbils. With age, the glomerular density decreased, the glomerular diameter increased, the basement membrane of renal tubules thickened, and the fibrous components between renal tubules increased. ConclusionThe histological structure of Mongolian gerbil's kidney varies with age, which may be related to glomerulosclerosis and parenchymal cell reduction. The specific mechanism needs further study.

This study explores the effects of enhancing the definitive hematopoiesis(DH)signals during the differentiation of human embryonic stem cells(hESCs)into hematopoietic stem/progenitor cells on the generation efficiency and effector function of natural killer(NK)cells generated from hESCs(also known as hESC-NK cells).The hESC(H1)were transformed into embryoid bodies(Ebs)by centrifugation,and during the induction of K562,were used to analyze the efficiency of hematopoietic differentiation,the efficiency of NK cell generation from hESC,the in vitro effector functions,and the expression of effector function related surface receptors.Compared to the control group,the DH group had a significant increase in the number of arterial hematopoietic endothelial cells(CD34+DLL4+)and a significant decrease in primitive hematopoietic related cells(CD34-CD43+)on day 8 of hematopoietic differentiation(P<0.05).On day 28 of NK cell differentiation,the DH group demonstrated a significant increase in the number of NK cells(CD45+CD56+),while a slight increase in the expression of effector function-related molecules such as IFN-γ,Granzyme B,Perforin and CD107a without statistical significance.Furthermore,the activation receptors CD16a and CD69 were significantly increased,NKP46 was significantly decreased,the inhibitory receptor NKG2A was significantly increased,while CD96 was significantly decreased on hESC-NK cells of DH groups(P<0.05).Conclusively,enhancing the signals for definitive hematopoiesis during hESC differentiation into hematopoietic stem/progenitor cells significantly improves the yield of NK cells and the expression of CD16a without affecting their in vitro effector functions.Our study provides a new approach to improving the efficiency of hESC-NK cell or iPSC-NK cell generation.

Objective: To examine the prevalence and factors influencing the inconsistency for knowledge and behavior in condom use among college students, so as to provide suggestions for AIDS prevention and education in universities. Methods: From October to December 2019, a multistage cluster sampling method was employed to collect data relating to inconsistency for knowledge and behavior in condom use and other related factors among 1 303 students from six colleges in Zhuhai, China. Chi square test and Logistic regression were performed to analyze the influencing factors and moderating effect. Results: The reporting rate of in consistency of knowledge and behavior in condom use among college students was 41.1%. Multivariate Logistic regression analysis showed that seeking sexual partners offline was negatively correlated with inconsistency for knowledge and behavior in condom use ( OR=0.70, 95%CI =0.51-0.95). However, condom nonuse during the first sexual experience (OR=7.11, 95%CI=5.23-9.67), smoking before sex ( OR=1.47, 95%CI =1.07-2.02), drinking before sex ( OR=1.44, 95%CI =1.09-1.91), history of intimate partner violence ( OR=1.53, 95%CI =1.13-2.07), and having multiple sexual partners ( OR=1.69, 95%CI =1.25-2.29) were positively correlated with inconsistency for knowledge and behavior in condom use ( P <0.05). The moderating effect analysis showed that condom use during the first sexual experience had a moderating effect on smoking before sex and inconsistency for knowledge and behavior in condom use ( β=0.92, P <0.05). Among students who did not use condoms during the first sexual experience, a positive correlation was observed between smoking before sex and inconsistency for knowledge and behavior in condom use ( OR= 2.76 , 95%CI=1.09-6.99, P <0.05). However, no correlation was found between smoking before sex and inconsistency for knowledge and behavior in condom use ( OR=1.32, 95%CI=0.92-1.88, P >0.05) among students who used condoms during the first sexual experience. Conclusion High levels of inconsistency for knowledge and behavior in condom use are found among college students in Zhuhai City. Colleges should carry out sex education activities as soon as possible, and explore new health education models to promote the transformation of their knowledge into behavior.