It is difficult to treat malignant tumors, neurodegenerative diseases, and vascular diseases. For pathogenesis complexity of these diseases, researchers have focused on finding more drugs with high efficacy and low side effects. As a potential first-in-class drug, RRx−001 is expected to be an important first-line drug in tumor immunology, radiosensitizer and radio protecter. Currently, RRx−001 entered phase Ⅲ clinical trials. The data of the phase Ⅱ clinical trials demonstrated its safety and effectivity as a single agent and in combination with first-line clinical drugs. The novel mechanisms of RRx−001 and the result of main clinical trials were summarized, which could be valuable to further optimization and clinical application.

ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess， and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 （STAT3）/vascular endothelial growth factor （VEGF） signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine， 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method， with 30 cases in each group. The control group received conventional treatment， while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7^th， 14^th and 21^st day after operation， enzyme-linked immunosorbent assay （ELISA） was used to measure the expression levels of serum interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）. Hematoxylin eosin （HE） staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 （p-STAT3） and vascular endothelial growth factor （VEGF） proteins， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain， secretion volume score， and healing rate of patients on the 3^rd， 7^th， 14^th， and 21^st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group （P<0.05）. For intra-group comparison， the pain score of the control group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The secretion volume score decreased on the 14^th and 21^st days after operation （P<0.05）. The pain score and secretion volume score of the treatment group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The levels of various inflammatory factors decreased in both groups （P<0.05）. Compared with those on the surgical day， the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7^th and 21^st days after operation （P<0.05）. There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period （P<0.01）. For inter-group comparison， on the 7^th and 14^th days after operation， the pain score in the treatment group was lower than that in the control group. On the 7^th， 14^th and 21^st days after operation， the secretion volume scores and healing rate of the treatment group were better than those of the control group （P<0.05）. The levels of various inflammatory factors in the treatment group were lower than those in the control group （P<0.05）， and the decline rate was faster （P<0.05）. On the 7^th day after operation， the levels of p-STAT3， VEGF protein， and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group （P<0.05）. HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly， and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery， reduce secretions， and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β， IL-6， and TNF-α， reducing the inflammatory response of the wound， upregulating the expression of p-STAT3 and VEGF proteins， and stimulating the STAT3/VEGF signaling pathway， thereby accelerating angiogenesis and promoting wound healing.

High-field magnetic resonance imaging (MRI), typically referring to systems with a magnetic field strength of ≥ 3 Tesla (T), offers significant advantages over conventional MRI in terms of higher signal-to-noise ratio (SNR) and improved resolution. These advantages have opened new prospects for the assessment of kidney diseases. This review summarizes the application progress of high-field MRI in evaluating kidney diseases, focusing on advanced techniques for refined assessment of renal anatomy and function, including arterial spin labeling (ASL) perfusion imaging, blood-oxygen-level-dependent (BOLD) oxygenation imaging, sodium (23Na) imaging, and quantitative evaluation of renal fibrosis. Furthermore, the review explores the value of high-field MRI in the diagnosis of renal tumors and kidney stones, tumor characterization, and its role in supporting treatments such as percutaneous nephrolithotomy (PCNL). Specifically, high-field MRI provides new approaches for early diagnosis and accurate staging of renal tumors, as well as radiation-free detection, composition analysis, and preoperative planning for PCNL in kidney stones. Finally, the review discusses current technical challenges, practical issues such as equipment accessibility, and future development directions. High-field MRI is emerging as a powerful non-invasive tool, providing crucial support for improving the diagnosis, management, and research of kidney diseases.

BackgroundCurrent studies on the relationship between depressive symptoms and the risks of stroke and all-cause mortality mostly focus on the elderly population or high-risk groups with chronic diseases. The long-term impact of depressive symptoms in young and middle-aged people on the risks of stroke and all-cause mortality still lacks systematic assessment， and the relevant evidence is insufficient. ObjectiveTo explore the association between depressive symptoms and the risks of stroke and all-cause mortality in young and middle-aged adults， thereby expanding the risk evidence in this age group and providing epidemiological basis for early identification of high-risk individuals and the development of targeted intervention strategies. MethodsBased on data from the National Health and Nutrition Examination Survey （NHANES） database （2009–2018）， a total of 14 947 young and middle-aged respondents aged 18 to 64 were included as the research subjects. Logistic regression and restricted cubic spline （RCS） models were employed to examine the association between depressive symptoms and stroke. Cox proportional hazards model， RCS model， and Kaplan-Meier （K-M） survival curves were used to clarify the relationship between depressive symptoms and all-cause mortality risk. To verify the robustness of main findings， sensitivity analysis was conducted stratified by gender， hypertension， diabetes， hyperlipidemia， body mass index （BMI）， and age. ResultsLogistic regression analysis revealed that compared with the non-depressed group， the risk of stroke in the mild depression group increased by 53.50% （OR=1.535， 95% CI： 1.147–2.053）， while the moderate-to-severe depression group showed the highest risk with a 132.90% increase （OR=2.329， 95% CI： 1.733–3.129）. RCS analysis indicated an approximately linear dose-response relationship between PHQ-9 score and the risk of stroke （P_{for non-linearity}=0.089）， with stroke risk increasing as PHQ-9 scores rose. As the PHQ-9 score increased， the risk of stroke also showed an upward trend. Cox regression analysis demonstrated that compared with the non-depressed group， the risk of all-cause mortality in the mild depression group increased by 48.80% （HR=1.488， 95% CI： 1.164–1.902）， and the moderate-to-severe depression group had a 70.60% increased risk （HR=1.706， 95% CI： 1.310–2.221）. RCS analysis showed a linear dose-response relationship between PHQ-9 scores and all-cause mortality risk （P_{for non-linearity}=0.440）. K-M curves indicated that as the severity of depressive symptoms increases， the risk of all-cause mortality gradually rises （P<0.05）. Sensitivity analysis confirmed that the associations between depression symptoms and risks of stroke and all-cause mortality were not modified by gender， hypertension， diabetes， hyperlipidemia， BMI， or age， demonstrating robust findings. ConclusionAmong the young and middle-aged population， both mild and moderate-to-severe depression were associated with increased risks of stroke and all-cause mortality， with the moderate-to-severe depression group showed more pronounced risk elevations. A positive dose-response relationship was observed between depressive symptoms and these risks.

AIM:To study the efficacy and molecu-lar mechanism of PX-478 in enhancing radiotherapy effect of lung cancer.METHODS:H460,A549 cells were divided into blank group,radiation group and radiation combined PX-478 group.In addition to the blank group,the radiation group and the PX-478 group were given 2Gy X-ray irradiation to estab-lish the radiation model,and the radiation com-bined with the PX-478 group was given 20 μmol/L PX-478 intervention after modeling,and cultured for 24 h.Inverted microscope was used to observe cell growth and cell number,CCK-8 method was used to detect cell viability,cloning was used to ob-serve cell proliferation,flow cytometry was used to detect cell apoptosis,and Western blot was used to detect HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA pro-tein expression.RESULTS:Compared with blank group,the number of H460,A549 cells in radiation group decreased,cell viability and proliferation abil-ity decreased,cell apoptosis rate increased,HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression increased(P＜0.01).Compared with the radiation group,the number of H460,A549 cells in the radia-tion combined PX-478 group was significantly de-creased,the cell viability and proliferation ability were significantly weakened,the apoptosis rate was significantly increased,and the protein expres-sions of HIF-1α,GLUT1,HK2,PFK1,PKM2 and LDHA were significantly decreased(P＜0.01).CONCLU-SION:PX-478 can regulate the HIF-1α-mediated gly-colysis in A549,H460 cells after radiation,regulate the energy metabolism,increase the apoptosis of tumor cells,and improve the effect of radiotherapy.

AIM:To explore the efficacy and safe-ty of two drugs in diagnosed idiopathic membra-nous nephropathy(IMN).METHODS:A retrospec-tive study was conducted on 113 patients diag-nosed with IMN by renal biopsy or PLA2R antibody positive at the department of nephrology,yijishan hospital,wannan medical college from november 2019 to July 2024,of whom 55 received cyclophos-phamide treatment and 58 received rituximab treatment,and follow-up was ≥6 months.RESULTS:At 6 months,38 patients(69.09％)in the cyclophos-phamide treatment group and 36 patients(62.07％)in the rituximab treatment group had achieved a combined response(complete or partial response).At 12 and 18 months,there was no statistical differ-ence in the combined response rate between the two groups(70.83％vs.83.87％,P=0.186 and 73.68％vs.73.68％,P=1.000),but at 12 months,the combined response rate in the rituximab group was higher than that in the cyclophosphamide group.In IMN patients with eGFR＜60 mL/(min·1.73 m2),rituximab significantly improved renal function(P=0.008).Over the entire follow-up peri-od,the total number of adverse events was higher in the cyclophosphamide group than in the ritux-imab group(57 vs..45),and the incidence of non-serious adverse events was higher than in the ritux-imab group(P=0.039).CONCLUSION:The efficacy of rituximab in the treatment of IMN is not inferior to that of cyclophosphamide,and it has better safety.Rituximab improved renal function better than cy-clophosphamide in patients with eGFR＜60 mL/(min·1.73 m2)IMN.

Objective:To analyze the four lab test results of infectious diseases among patients in a stomatological hospital in Shaanxi Province from 2018 to 2023,so as to provide evidence for clinical prevention and control of infection.Methods:The pa-tients who see a doctor in stomatological hospital from January 2018 to December 2023 were tested for four infectious diseases.HB-sAg and anti-HIV were detected by electrochemical luminescence method,and anti-HCV and anti-TP were detected by ELISA method.Results:There was no statistical difference in the positive rates of HBsAg,anti-HCV and anti-HIV in each year,and the positive rate of anti-TP decreased year by year.There was no statistical difference in the positive rate of anti-HCV between different sexes,and the positive rates of HBsAg,anti-TP and anti-HIV are higher in male than in female.HBsAg and anti-HCV positive pa-tients were mostly concentrated in 51-60 years old.Anti-TP positive patients were mostly concentrated in people over 60 years old and anti-HIV positive patients were mostly concentrated in 41-60 years old.78.38％of HIV-positive patients with oral mucosal dis-eases were initially diagnosed as oral candidiasis.Conclusion:Male and people over 41 years old were the high-risk groups of vari-ous infectious diseases.

Objective To investigate how KHSRP regulates the malignant development process of cardia gastric cancer through JAK1/STAT3 signaling pathway,and to reveal the molecular mechanisms.Methods Quantitative real-time fluores-cence polymerase chain reaction(qRT-PCR)was used to detect KHSRP in cancer cell lines(MKN-28,OE-33,HGC-27,KYSE-50,CRL-5822,SNU-1)as well as human normal epithelial cell lines(GES-1).Cell counting kit-8(CCK-8)and Transwell assay were used to detect the biological characteristics of cell proliferation,migration and invasion,respectively.Experimental subjects were divided into four groups in cellular and animal experiments:Sh-KHSRP group(KHSRP knockdown group),Sh-NC group(KHSRP control group),KHSRP group(KHSRP overexpression group),Vector group(KHSRP control group).The expres-sion levels of JAK/STAT and KHSRP proteins in stably transfected cells were detected by Western blotting.The mRNA and protein expression levels of KHSRP in different experimental groups were determined by real-time fluorescence quantitative PCR.Nude mouse experiments were performed to analyze the role of KHSRP in living animals.Results The qRT-PCR showed that the expression of KHSRP was significantly elevated in cancer cell lines(MKN-28,OE-33,HGC-27,KYSE-50,CRL-5822,SNU-1)and tumor tissues compared with human normal epithelial cells(GES-1)and tissues.The results of cell function experi-ments showed that knockdown of OE-33 and HGC-27 cell lines(sh-KHSRP group)significantly inhibited cell proliferation,mi-gration,and invasive ability,whereas the control group(sh-NC group)did not exhibit this inhibitory effect.These features were significantly enhanced in KHSRP overexpressing cells.In nude mice experiments,knockdown of KHSRP in nude mice led to re-duction in tumor volume and weight,lower cell proliferation rate,and lower number of lung nodal metastases compared with the control group(sh-NC group).These changes were reversed while KHSRP was overexpressed.Signaling pathway experiments showed that the expression of JAK1 and STAT3 was significantly downregulated in the sh-KHSRP group compared to the sh-NC group,with opposite results in the overexpression group.The results of cell rescue assay indicated that KHSRP promoted the proliferation,migration and invasion ability of cardia gastric cancer cells by regulating the JAK1/STAT3 signaling path-way.Conclusion KHSRP promotes the malignant process of cardia gastric cancer metastasis by regulating the JAK1/STAT3 signaling axis.

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 squa-mous cell carcinoma organoid bank,ZL202311378598.3).Through groundbreaking optimization of cul-ture media,enzymatic digestion kinetics,and stepwise cryopreservation,we achieved a biobanking suc-cess 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 as-says;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 transi-tion(pEMT).This"holographic patient-mirroring"platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Techni-cal Guidelines(Technical guideline for establishing patient-derived oral squamous cell carcinoma or-ganoid banks,CHSA 2024-08).Future integration of immune-competent organoids,3D-bioprinted vas-culature,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.

BACKGROUND:Human endometrial mesenchymal stem cells can directly repair the damaged endometrium,promote angiogenesis,and restore the morphological structure of the uterus.However,after the direct injection of stem cells into the damaged endometrium,the cell survival rate is low,the retention time is short,and the repair effect is limited.OBJECTIVE:To observe the effect of polycaprolactone-hyaluronic acid electrospinning membrane combined with human endometrial mesenchymal stem cells on endometrial injury in rats.METHODS:(1)Cell experiment:Human endometrial mesenchymal stem cells were extracted by collagenase digestion method.Polycaprolactone-hyaluronic acid electrospinning membrane was prepared by electrospinning technology.The human endometrial mesenchymal stem cells were inoculated on polystyrene culture plate and polycaprolactone-hyaluronic acid electrospinning membrane.The proliferation and adhesion of the cells were observed by DNA quantitative analysis,WST-1 cell activity test,phalloidin staining,and scanning electron microscopy.The mRNA expressions of CD90 and Meflin in electrospun membrane were detected by qRT-PCR.(2)Animal experiments:27 female SD rats in estrus were selected to establish uterine adhesion model by mechanical scratching method and randomly divided into three groups with nine rats in each group:The blank control group did not receive any treatment;the control group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane;the experimental group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell mesh.Samples were collected at 3,7,and 14 days after surgery.Hematoxylin-eosin staining was used to observe the morphological structure of uterus and the number of glands.qRT-PCR and immunofluorescence staining were used to observe the expression of CD31 and vascular endothelial growth factor in uterine tissue.RESULTS AND CONCLUSION:(1)Cell experiment:Compared with polystyrene culture plate,polycaprolactone-hyaluronic acid electrospinning membrane could promote the proliferation and adhesion of human endometrial mesenchymal stem cells.Polycaprolactone-hyaluronic acid electrospinning membrane supported the expression of CD90 and Meflin genes of human endometrial mesenchymal stem cells.(2)Animal experiments:Hematoxylin-eosin staining showed that polycaprolactic-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell patch could promote the recovery of endometrial morphological structure after injury.The endometrial thickness and number of gland on day 14 after surgery were higher than those in blank control group and control group(P<0.05).qRT-PCR and immunofluorescence staining showed that the mRNA and protein expressions of CD31 and vascular endothelial growth factor in the experimental group were higher than those in the blank control group and the control group at 7 and 14 days after surgery(P<0.05).(3)The results showed that polycaprolacton-hyaluronic acid electrospinning membrane could improve the survival rate of stem cells and prolong the contact time between stem cells and the damaged tissue,and the composite transplantation of the two could better repair the damaged endometrial tissue.