Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

BackgroundDepression is a prevalent emotional problem in adolescents， and parental psychological control is an important predictor of adolescent depression. However， existing research on the acting mechanism between the two is not adequate. ObjectiveTo explore the pathway of negative perfectionism and academic stress between parental psychological control and depressive symptoms among secondary school students， so as to provide references for reducing the incidence risk of depression in such population. MethodsFrom February to April 2023， 1 100 students across 2 middle schools and 2 high schools in Zhongshan city were selected as subjects. The survey was conducted adopting Parental Psychological Control Questionnaire， Chinese Frost Multidimensional Perfectionism Scale （CFMPS）， sense of academic stress subscale in Mental Health Inventory of Middle School Student （MMHI-60） and Center for Epidemiological Studies-Depression Scale （CES-D）. Spearman correlation analysis was adopted to examine the correlation between scores of all scales above， and Amos 24.0 was used to test the mediating path of negative perfectionism and academic stress between parental psychological control and depressive symptoms among secondary school students. ResultsAmong the 1 009 valid questionnaires withdrew （91.73% of the total）， 261 students were detected to have depressive symptoms （25.87%）. As the results of Spearman correlation analysis showed， the scores of the Parental Psychological Control Questionnaire， score of negative perfectionism dimension in CFMPS， score of sense of academic stress subscale in MMHI-60 and CES-D score were positively correlated with each other （r=0.323~0.644， P<0.05 or 0.01）. The direct effect value of parental psychological control on depressive symptoms in secondary school students was 0.128 （95% CI： 0.061~0.201）， accounting for 31.37% of the total effect. Negative perfectionism and academic stress played independently as intermediatory roles between parental psychological control and depressive symptoms in secondary school students， and the indirect effect values were 0.099 （95% CI： 0.068~0.133） and 0.100 （95% CI： 0.060~0.143）， accounting for 24.27% and 24.51% of the total effect， respectively. Negative perfectionism and academic stress acted combinedly as the chain effect pathway between parental psychological control and depressve symptoms in secondary school students， with the indirect effect value of 0.081 （95% CI： 0.060~0.106） accounting for 19.85% of the total effect. ConclusionParental psychological control can affect the depressive symptoms among secondary school students directly， and through independent or chain paths of negative perfectionism and academic stress indirectly. ［Funded by Zhongshan Social Welfare Technology Research Project （number， 2022B1060）］

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

OBJECTIVE To investigate of the regulatory effects of Budi Shenlian Recipe on gut microbiota and the phenotypic transition of tumor-associated macrophages(TAMs)in colorectal cancer(CRC)mice.METHODS Forty male BALB/c mice were divided into blank control group,model group,positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group(n=8).CRC-bearing models were established by subcutaneous injection of CT26 cells.Additionally,10 male BALB/c mice were divided into the Budi Shenlian Recipe fecal microbiota transplantation(BFMT)group and model fecal microbiota transplantation(MFMT)group(n=5).The gut microbiota of these mice was cleared using a mixed solution of quadruple antibiotics,followed by subcutaneous injection of CT26 cells to construct pseudo-germ-free CRC-bearing mice.Fecal samples from the model group and high-dose Budi Shenlian Recipe group were collected to prepare fecal microbiota solutions.The BFMT group received gavage with fecal microbiota solution from the high-dose Budi Shenlian Recipe group,while the MFMT group received gavage with fecal micro-biota solution from the model group.Tumor volume changes were observed and recorded.HE staining was used to assess pathological changes in tumor tissues.16S sequencing was performed to analyze changes in gut microbiota.Flow cytometry and immunofluorescence staining were used to evaluate the proportion of M1/M2 type TAMs in tumor tissues.ELISA was used to detect differences in TNF-α and IL-10 levels in tumor tissues.RESULTS Compared to the model group,the tumor volume of mice in the positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group grew more slowly(P<0.01).HE staining showed necrotic areas in tumor tissues and reduced mitotic figures in the positive control and Budi Shenlian Recipe groups compared to the model group.16S rRNA sequencing showed no significant differences in Chao1 and ACE indices between the high-dose Budi Shenlian Recipe group and the model group.PCoA analysis indicated a distinct microbial community structure between the blank group and mod-el group,with the microbial structure of CRC mice in the Budi Shenlian Recipe group closer to that of the blank group.Compared to the blank group,the model group showed a significant decrease in the proportion of Muribaculaceae,Muribaculum,Alloprevotella,and Prevotellaceae_UCG-001,and a significant increase in Lachnospiraceae_NK4A136_group,Bacteroides,and Helicobacter.After admin-istering Budi Shenlian Recipe to CRC mice,the community structure of some mice partially reverted to the level of the blank group.Transcriptome sequencing revealed that the most significant biological process(BP)among upregulated genes was the negative regulation of macrophage migration,suggesting that Budi Shenlian Recipe can reduce macrophage migration.Moreover,compared to the model group,the proportion of TAMs cells in the tumor tissues of the Budi Shenlian Recipe group significantly decreased(P<0.001).Simultaneously,compared to the model group,the proportion of M1 type TAMs in the Budi Shenlian Recipe group significant-ly increased(P<0.000 1),while the proportion of M2 type TAMs significantly decreased(P<0.05).Immunofluorescence analysis showed the same trend as flow cytometry.The content of TNF-α in tumor tissues of the Budi Shenlian Recipe group significantly in-creased(P<0.001),and IL-10 content significantly decreased(P<0.001).Additionally,compared to the MFMT group,the tumor volume in the BFMT group grew more slowly(P<0.0001).HE staining showed increased necrotic areas,sparser cell arrangement,and reduced pathological mitosis in the BFMT group.Furthermore,compared to the MFMT group,the proportion of TAMs cells in the tumor tissues of the BFMT group significantly decreased(P<0.01).Compared to the MFMT group,the proportion of M1 type TAMs cells in the BFMT group increased(P<0.000 1),while the proportion of M2 type TAMs cells decreased(P<0.01).Immunofluores-cence analysis further confirmed that Budi Shenlian Recipe fecal microbiota transplantation can reduce the proportion of TAMs in the tumor tissues of CRC mice and promote the conversion from M2 to M1 type,thereby reducing immune suppression in the tumor micro-environment.CONCLUSION Budi Shenlian Recipe can improve gut microbiota dysbiosis in CRC mice and exert anti-CRC effects by reducing tumor infiltration of TAMs and modulating the phenotypic transition of TAMs.There may be a certain correlation between these two effects.

The development of malignant tumors is influenced by multiple factors,including genetics,environment,lifestyle,and pathogen infection.Viral infection plays a significant role in tumor development and progression.This article integrates the common pathways of seven oncogenic viruses(HPV,EBV,HBV,HCV,KSHV,HTLV-1,and HIV)based on the theory of cancer toxin pathomechanism.The findings reveal that cancer toxin formation is influenced by both internal factors(healthy qi deficiency,viscus dysfunction,and qi,blood,and body fluid stagnation)and external factors(viral infection,environmental factors,and the six exogenous pathogens),driving tumor development,metastasis,and recurrence.Viral infection not only provides the material foundation for cancer toxin but also accelerates its maturation and spread through chronic inflammation and immune imbalance,forming a complex pathogen-esis of"viral toxicity-endogenous cancer toxin",which translates into a three-stage strategy of"prevention,treatment,and post-recovery prevention".This article systematically discusses the pathogenesis of major cancer toxins and their associated tumors.Inte-grating the cancer toxin theory,the article explores preventive and therapeutic strategies for virus-associated malignancies,providing a theoretical basis and practical reference for the integrated prevention and treatment of tumors using traditional Chinese and Western medicine.

OBJECTIVE To investigate the inhibitory effect mechanism of Anzheng Kangliu Decoction against colorectal cancer by suppressing glycolysis through regulation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.METHODS Human colorectal cancer SW620 cells were treated with Anzheng Kangliu De-coction,and cell proliferation and migration abilities were assessed.Forty-two BALB/c nude mice were randomly divided into a blank control group,model group,5-fluorouracil(5-FU)group(0.025 g·kg-1),Anzheng Kangliu Decoction low-dose group(7.67 g·kg-1),medium-dose group(15.34 g·kg-1),and high-dose group(30.68 g·kg-1).The inhibitory effect of Anzheng Kan-gliu Decoction on subcutaneous xenograft tumors was evaluated by observing body weight,tumor volume,tumor mass,HE staining,im-munohistochemical staining of Ki67 and other indicators.High-throughput transcriptome sequencing was performed to identify differen-tially expressed genes and pathways in tumor tissues between the model group and the Anzheng Kangliu Decoction medium-dose group,elucidating the potential mechanism of Anzheng Kangliu Decoction against colorectal cancer.Glucose and lactate assay kits were used to measure glucose consumption and lactate production in SW620 cells and tumor tissues after Anzheng Kangliu Decoction intervention.Western blot was employed to detect the expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,hexokinase 2(HK2),and lactate dehydrogenase A(LDHA)in SW620 cells and tumor tissues following Anzheng Kangliu Decoction treatment.RE-SULTS In vitro cell experiments demonstrated that,compared with the blank control group,Anzheng Kangliu Decoction intervention significantly inhibited the proliferation and migration of SW620 cells(P<0.01),reduced glucose consumption and lactate production(P<0.05,P<0.01),and downregulated the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).In vivo animal experiments revealed that,compared with the model group,Anzheng Kangliu Decoction suppressed the growth of subcutaneous xenograft tumors in nude mice(P<0.01),increased tumor tissue necrosis,decreased glucose consumption and lactate production in tumor tissues(P<0.05,P<0.01),and reduced the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).CONCLUSION Anzheng Kangliu Decoction exerts an in-hibitory effect on colorectal cancer,and its mechanism may be associated with the suppression of glycolysis through regulation of the PI3K/Akt/mTOR signaling pathway.

Objective To explore the impact of gender factors in participant selection during bioequivalence studies,and to provide insights for improving the screening success rate in subsequent trials.Methods A retrospective study was con-ducted to summarize the screening information of healthy subjects in the bioequivalence study conducted in the Phase Ⅰ Clinical Trial Laboratory of the Affiliated Hospital of Xiangnan University from July 2021 to July 2023.The number of failed screening ca-ses in different stages of screening for each project was counted,and the influence of gender factors on subject screening was ana-lyzed.Results A total of 32 bioequivalence studies involving 2 794 subjects,including 1 816 males and 978 females,were in-cluded in the study.The proportion of males was higher in vital signs and BMI abnormalities,and the proportion of females was higher in ECG abnormalities and active withdrawal,and the pass rate was lower in males than in females(40.0％ vs.45.8％),and the existence of the two was statistically significant(P＜0.05).The results of PC A showed that the distribution of data in males was more dispersed,and the distribution of data in females was centralized,and the two could be clearly differentiated.Binary lo-gistic regression analysis showed significant differences between males and females in laboratory test screening failures and BMI(P＜0.05).Further analysis showed that the screening failure rates of blood biochemistry,urine routine,coagulation function and blood transfusion were higher in males than in females,but the screening failure rates of blood routine were lower than those of fe-males.Conclusions Gender is an important influencing factor in the screening process of bioequivalence studies.Including subjects with appropriate gender ratios can help improve enrollment speed and reduce clinical trial costs.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.