Objective: To explore the association between meat consumption and anxiety symptoms in first year junior high school students in Yunnan Province, and to provide theoretical support for preventing and relieving anxiety symptoms in junior high school students. Methods: From October to December 2022, a random cluster sampling method was used to select 8 500 first year junior high school students from 11 counties in Yunnan Province as the survey subjects for a questionnaire survey. The study used Food Frequency Questionnaire and the Chinese version of the Depression Anxiety Stress Scale-21 (DASS-21) to assess the meat consumption and anxiety symptoms of junior high school students.The distribution differences in anxiety symptoms among first year junior high school students with different demographic characteristics were analyzed statistically by using the Chi-square test,and the association between meat consumption and anxiety symptoms in students was analyzed by using a generalized linear model. Results: The detection rate of anxiety symptoms was 48.47%. After controlling for demographic variables and confounding factors, the consumption of livestock meat, poultry meat, processed meat, cured meat, barbecued meat and raw skin meat was statistically significant with anxiety symptoms ( β =-0.05, 0.04, 0.04, 0.08, 0.14, 0.17, all P <0.05). Stratified by ethnicity, The consumption of livestock meat, cured meat and barbecue was statistically correlated with anxiety symptoms in Han adolescents ( β =-0.07, 0.14, 0.22 ); the consumption of processed meat and raw skin meat was statistically correlated with anxiety symptoms in ethnic minority adolescents ( β =0.08, 0.18) (all P <0.05). Conclusions There is a statistical association between meat comsumption and the risk of anxiety symptoms in first year junior high school students in Yunnan Province. Guidance on meat consumption should be strengthened to prevent the occurrence of anxiety symptoms.

ObjectiveTo investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

Abstract Improving the coping ability of parents of adolescents with non-suicidal self-injury (NSSI) can help reduce the frequency of NSSI, improve the quality of life of adolescents with NSSI, and alleviate the physical and psychological burden on their parents. The review summarizes the concept and significance of parental coping ability among adolescents with NSSI, as well as the current status of research and intervention strategies in China and abroad, with the aim of providing a reference for relevant research.

ObjectiveTo investigate the clinicopathological features， molecular profile， treatment response， and prognosis of SMARCA4 （BRG-1） and SMARCB1 （INI-1）-deficient undifferentiated tumors of the digestive system， aiming to enhance the understanding of this rare and highly aggressive molecular subtype. MethodsThis study is a single-center retrospective analysis. We included 9 cases of malignant digestive system tumors with loss of BRG-1 expression and 3 cases with loss of INI-1 expression， all pathologically confirmed at Sun Yat-sen University Cancer Center between April 2022 and December 2025. By reviewing clinical data， histological morphology，immunohistochemistry and next-generation sequencing （NGS） results from partial cases， we systematically summarized their clinicopathological and molecular characteristics， treatment strategies， and survival outcomes. Results​ Among the 12 patients， 6 were male and 6 were female， with a median age of 62 （44-70） years. 9 cases exhibited SMARCA4 deficiency， and 3 cases exhibited SMARCB1 deficiency. Tumors originated in the stomach （5 cases）， colon （3 cases）， pancreas （1 case）， with the primary site unknown in 3 cases. The histology predominantly showed undifferentiated carcinoma， with 1 case of poorly differentiated carcinoma. The tumor cells were epithelioid with significant atypia. Epithelial markers （e.g. CKpan） were often lost or markedly decreased， while vimentin could be positive. All 9 cases tested for MMR status were mismatch repair proficient （pMMR）， and the Ki-67 proliferation index was high ［median 80% （60%-90%）］. A discordance was observed between IHC findings and NGS results in the 6 sequenced cases. The NGS profiling revealed frequent co-occurring mutations， including TP53， KRAS， and NRAS， with no germline mutations identified.The median follow-up time was 277 （55-867） days. 9 of the 12 patients presented with stage Ⅳ disease at the time of initial diagnosis. Among 3 newly diagnosed patients without metastasis who received treatment， 2 achieved prolonged recurrence-free survival. Patients with advanced disease at initial diagnosis primarily underwent platinum-based chemotherapy or combination regimens， yet their prognosis was generally poor， with a median overall survival of 60 （45-541） days， ranging from 16 to 867 days. Notably， several patients who received chemotherapy combined with targeted therapy and immunotherapy achieved extended survival. ConclusionSMARCA4/SMARCB1-deficient undifferentiated tumor of the digestive system is a distinct molecular subtype characterized by high aggressiveness and poor prognosis， predominantly affecting middle-aged and elderly individuals. Diagnosis relies on the immunohistochemical loss of BRG-1 or INI-1 proteins. While no standard of care currently exists， treatment often refers to regimens for adenocarcinoma of the primary site. Combined immunotherapy and targeted therapy may offer potential benefits， warranting further validation in large-scale prospective studies.

[Objective] To explore the strategy of blood management in patients with massive transfusion in the frigid plateau region. [Methods] The treatment process of a patient with liver rupture in the frigid plateau region was analyzed, and the blood management strategy of the frigid plateau region was discussed in combination with the difficulties of blood transfusion and literature review. [Results] The preoperative complete blood count (CBC) test results of the patient were as follows: RBC 3.14×10¹²/L, Hb 10⁶ g/L, HCT 30.40%, PLT 115.00×10⁹/L; coagulation function: PT 18.9 s, FiB 1.31 g/L, DD > 6 μg/mL, FDP 25.86 μg/mL; ultrasound examination and imaging manifestations suggested liver contusion and laceration / intraparenchymal hematoma, splenic contusion and laceration, and massive blood accumulation in the abdominal cavity; it was estimated that the patient's blood loss was ≥ 2 000 mL, and massive blood transfusion was required during the operation; red blood cell components were timely transfused during the operation, and the blood component transfusion was guided according to the patient's CBC and coagulation function test results, providing strong support and guarantee for the successful treatment of the patient. The patient recovered well after the operation, and the CBC test results were as follows: RBC 4.32×10¹²/L, Hb 144 g/L, HCT 39.50%, PLT 329.00×10⁹/L; coagulation function: APTT 29.3 s, PT 12.1 s, FiB 2.728 g/L, DD>6 μg/mL, FDP 25.86 μg/mL. The patient was discharged after 20 days, and regular follow-up reexamination showed no abnormal results. [Conclusion] Individualized blood management strategy should comprehensively consider the patient’s clinical symptoms, the degree of hemoglobin decline, dynamic coagulation test results and existing treatment conditions. Efficient and reasonable patient blood management strategies can effectively improve the clinical outcomes of massive transfusion patients in the frigid plateau region.

BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

AIM: To investigate the protective effect of β-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS: A dry ARMD mouse model was established by NaIO3 injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD.

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*