Objective: To analyze the factors associated with high level fear of negative evaluation (FNE) among junior high school students and to construct a nomogram risk prediction model, so as to provide scientific tools for psychological health intervention for junior high school students. Methods: A convenience sampling combined with cluster random sampling method was used to select 5 485 junior high school students from 4 cities (Wuhan, Huanggang, Xianning and Xiaogan) for an online questionnaire survey in March 2025. The total sample was randomly split into a training set ( n =3 839) and a validation set ( n =1 646). Univariate analysis was performed in the training set using Chi-square test and t-test. Variables with statistical significance were subsequently included in multivariate Logistic regression to identify independent predictors and to construct a nomogram based risk prediction model. The discriminative ability and clinical utility of the model were evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: There were 1 649 junior high school students with low level FNE and 2 190 with high level FNE in the training set. The self control ability of junior high school students with lowlevel and high level FNE showed a statistically significant difference (23.96±3.96, 21.48±3.37, t=25.15, P < 0.01 ). Statistically significant differences in the detection rate of high level FNE were observed among junior high school students with different genders, family types, parenting styles, academic rankings, psychological flexibility, mobile phone addiction tendencies, emotional management training, exercise frequency, left behind experiences, and places of origin ( χ 2=82.01- 1 126.68 , all P <0.01). The results of Logistic regression analysis revealed that, the following factors were identified as significant factors influencing high level FNE among junior high school students:exercise frequency ( OR=0.21, 95%CI =0.17-0.26); parenting style ( OR=0.48, 95%CI =0.40-0.58); left behind experience ( OR=3.88, 95%CI =3.27-4.61); smartphone addiction proneness ( OR=2.19, 95%CI =0.89-0.93); self-control ability ( OR=0.91, 95%CI =0.89-0.93); and psychological flexibility ( OR=0.16, 95%CI =0.10-0.28) (all P <0.05). The AUC for the training and validation set were 0.88 (95% CI =0.87-0.89) and 0.87 (95% CI =0.85-0.89), respectively. The Hosmer-Lemeshow goodness of fit test yielded χ 2=8.57, 15.20 (both P >0.05). Conclusion The risk prediction model with high level FNE demonstrates good accuracy and can assist educators and parents in timely screening of junior high school students with high level FNE, thereby providing a basis for implementing targeted interventions.

As essential concepts of the traditional Chinese medicine theory,"deficiency"and"toxin"have been enriched and developed continuously since Huangdi Neijing.By tracing back and combing"deficiency"and"toxin",this paper sums up their relationship,analyzes and explains their basic connotation,and discusses their extension.The"deficiency-toxin"theory has two meanings:it covers the pathological state of the human body with deficiency of vital qi and excess of pathogenic toxin,and it also refers to the pathological evolutionary process in which"deficiency"and"toxin"promote each other.Based on the connotation and dynamic pathogenesis of the"deficiency-toxin"theory,it is pointed out that this theory can be applied to the prevention and treatment of infectious diseases and chronic debilitating diseases,including the"inflammation-cancer transformation"of inflammatory bowel disease.Taking inflammatory bowel disease as an example and combining its Western medical background,this paper expounds on the pathogenesis and treatment of the"inflammation-cancer transformation"of inflammatory bowel disease,and provides a paradigm of"deficiency-toxin"theory guiding clinical research.

Wound healing is a complex process of biological integration in which the adverse conditions such as excessive inflammatory reactions, cell proliferation and migration disorders, and cellular secretion impairment can lead to refractory wounds. Characterized by complex etiology, protracted condition, and high morbidity and recurrence rate, refractory wounds severely impair patients′ physical and mental health. In clinical practice, refractory wounds are primarily treated with surgical debridement and skin transplantation, but there still exist problems such as large surgical wounds, prolonged recovery time, and high recurrence rate. In recent years, owing to the multipotent differentiation, immunomodulatory, and paracrine functions of stem cells, cell-assisted lipotransfer (CAL) technique, which involves intra-body injection of a mixture of autologous adipose-derived stem cells (ADSCs) and granular fat for refractory wound repair, has demonstrated promising application prospects. It is of great significance in its clinical application to clarify the mechanism of effects of CAL technique in refractory wound repair. The authors reviewed the research progress in the mechanism of effects of CAL technique in repairing refractory wounds to provide references for the research and treatment of refractory wounds.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4⁺Tnni1⁺ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.
Animals ; Mice ; Diploidy ; Heart ; Myocytes, Cardiac/metabolism* ; Cell Communication ; Gene Expression Profiling ; Mitochondria ; Regeneration ; Mammals/genetics*

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8⁺ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

AIM: To observe the effect of PCSK9 inhibitors on blood lipid levels and common inflammatory factors in patients with coronary heart disease. METHODS: The clinical data of 201 patients with coronary heart disease who were admitted to the Department of Cardiology of Shanghai East Hospital from April 2020 to June 2021 were retrospectively analyzed. The patients were divided into PCSK9 inhibitor treatment group (101 cases: statin + PCSK9 inhibitor) and control group (100 cases: statin treatment only) according to their medication status. Blood lipids, blood routine, CRP and FIB were re-examined after 1 month of treatment. The changes of blood lipids and inflammatory factors before and after treatment were compared. RESULTS: Before treatment, there was no significant difference in blood lipids, blood routine, CRP and FIB between the two groups (P> 0.05). The levels of sdLDL and Lp(a) were significantly decreased (P< 0.05); the levels of WBC, CRP, N and FIB were significantly decreased (P< 0.05). Compared with the control group, the levels of TC, HDL, LDL-C, CRP and FIB in the PCSK9 inhibitor group were significantly changed (P< 0.05), and the results were statistically significant. CONCLUSION: PCSK9 inhibitors can not only reduce LDL-C levels, but also reduce Lp(a) levels. PCSK9 inhibitors can reduce CRP and FIB levels, suggesting that it can partially improve inflammation in peripheral blood in patients with coronary heart disease.

Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution. Unfortunately, classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification. We developed a single-cell DNA library preparation method without preamplification in nanolitre scale (scDPN) to address these issues. The method achieved a throughput of up to 1800 cells per run for copy number variation (CNV) detection. Also, our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification (MDA) method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation. We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepato-cellular carcinoma (HCC). We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome. Furthermore, we observed that a minor clone of the primary tumor containing additional alterations in chro-mosomes 1q, 10q, and 14q developed into the dominant clone in the recurrent tumor, indicating clonal selection during recurrence in HCC. Overall, this approach provides a comprehensive and scalable solution to understand genome hetero-geneity and evolution.

Objective:To synthesize a new β-amyloid (Aβ) radioactive tracer (2-((2-6-[ 18F]fluoro-5-(methylamino)pyridin-2-yl)benzothiazol-6-yl)thio)ethanol ( 18F-FINH-Me), and evaluate its biological distribution and affinity to Aβ plaques. Methods:18F-FINH-Me was synthesized by GE FN automated module, and the quality control and stability of 18F-FINH-Me were determined with high performance liquid chromatography (HPLC). The biodistribution of 18F-FINH-Me was observed in normal C57BL/6 mice ( n=25). MicroPET/CT imaging was performed in Alzheimer′s disease (AD) model mice( n=5) and matched normal C57BL/6 mice( n=5). The brain tissues of mice were taken for Aβ immunohistochemical staining. 18F-FINH-Me autoradiography was performed in postmortem brain sections of one AD patient (female, 69 years old) and one healthy volunteer (female, 66 years old). Results:The decay correction yield of 18F-FINH-Me was (53±4)% ( n>20) with the radioactive purity of more than 98% ( n>20) and the specific activity of 79.90-122.00 GBq/μmol ( n=10). 18F-FINH-Me was stable in phosphate buffered solution (PBS) after incubation for 4 h at room temperature. The biodistribution showed that 18F-FINH-Me was mainly excreted through the liver and kidneys. MicroPET/CT imaging showed that 18F-FINH-Me was obviously uptaken in the brain of AD mice. After injection for 1-2 min, the uptake of 18F-FINH-Me reached the peak, and the elution speed was fast (whole brain standardized uptake value: 0.73±0.17 for 1 min, 0.31±0.06 for 30 min). The immunohistochemistry showed that there were abundant Aβ plaques in the brain of AD model mice but not in the normal C57BL/6 mice brain. The autoradiographic results showed that 18F-FINH-Me exhibited substantial plaque labeling in brain sections of one AD patient but not in the healthy volunteer. Conclusion:18F-FINH-Me may be an effective PET agent for detecting Aβ plaques in brain.