Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective: To explore the relationship between sleep characteristics, physical activity patterns, with depressive and anxiety symptoms in college students, so as to provide reference for student mental health promotion. Methods: From September to November 2023, a convenience sampling method was used to select 7 954 college students aged 18-22 years from 9 universities in Shanghai, Hubei, and Jiangxi. Assessments were conducted using the International Physical Activity Questionnaire Short-Form (IPAQ-SF), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI) to evaluate physical activity, depressive and anxiety symptoms, and sleep quality, respectively. Logistic regression analysis was employed to explore the impact of sleep characteristics and physical activity patterns on depressive and anxiety symptoms and their comorbidity among college students. Results: The detection rates for depressive symptoms, anxiety symptoms, and comorbid depression and anxiety symptoms were 25.67%, 35.39%, and 23.15%, respectively. Factors such as gender, grade, household registration, parental education level, annual family income, family structure, and dietary habits were all associated with the detection rates of depressive and anxiety symptoms and their comorbidity (χ2=4.41-118.39, P<0.05). Physical activity patterns, sleep duration, sleep quality, and sleepwake characteristics were also associated with the occurrence of depressive and anxiety symptoms and their comorbidity (χ2=9.66-627.70, P<0.05). Logistic regression analysis showed that college students who stayed up late and slept less than 7 had the highest risk of depressive and anxiety symptoms and their comorbidity (OR=1.93, 1.85, 1.88, P<0.05). Compared to regular physical activity patterns, insufficient physical activity patterns were associated with an increased risk of depressive and anxiety symptoms (all OR=1.18, P<0.05). Further stratified analysis results showed that the risk of depression, anxiety and their comorbidity increased in college students who stayed up late and slept less than 7 h, went to bed before midnight and slept less than 7 h, or went to bed before midnight and slept more than 7 h but did not have sufficient physical activity (P<0.05). Conclusions Sleep characteristics and physical activity patterns significantly affect depressive and anxiety symptoms in college students. Universities should strengthen sleep management and implement flexible physical activity interventions to help students establish healthy lifestyles.

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

By reviewing modern research and integrating clinical practice， this paper elucidates the correlation between the traditional Chinese medicine theory of pathological accumulation from collateral obstruction and gap junction intercellular communication （GJIC）， as well as its theoretical connotation and clinical application in tumor prevention and treatment. Physiologically， gap junction and collateral channels share similarities in structural distribution， substance exchange and information transmission. Pathologically， metabolic coupling mediated by dysfunctional gap junction resembles collaterals stagnation， forming the basis of tumor pathogenesis. The establishment of heterotypic gap junction parallels collateral hyperactivity， contributing to tumor metastasis. The post-translational modifications （PTMs） disorder of connexins is similar to the deficiency of collaterals， serving as a driver of tumor progression. Clinically， tumor treatment should follow the pathomechanism of collateral obstruction leading to pathological accumulation. In the early stage， detoxifying and unblocking collaterals can restore intercellular communication and inhibit tumorigenesis； in the progressive stage， calming hyperactivity and suppressing aberrant collateral pathways can prevent metastasis by interrupting heterotypic gap junction formation； and in the terminal stage， supporting vital qi and modulating PTMs of connexins can help delay tumor progression.

Objective Electrocardiogram(ECG)signal quality degrades when the level of activity is high and motion artifacts are severe.Poor quality signals may result in false alarms,poor patient monitoring,imprecise measurement,and misleading diagnosis.The quantitative assessment of ECG signal quality forms the basis of automatic ECG noise reduction and heart disease diagnosis.Methods The ECG signal quality index(SQI)was obtained by statistically analyzing the heartbeat similarity and the slope character,respectively,namely rSQI and kSQI.Results Using MIT-BIH Noise Stress Test Database to test,both rSQI and kSQI decreased when the Signal Noise Ratio(SNR)decreased,which revealed the ECG signal quality.Based on the quasiperiodic property,the waveform similarity,as a beat-to-beat index,is obtained by cross correlation between two ECG cycles with high precision but heavy computation.Slope-based method dispenses with QRS detection and is very simple and real-time,but its sensitivity is lower than similarity-based method and it only get statistical data.Conclusion Both morphology similarity and slope character algorithms could provide objective estimation of ECG quality.Slope-based method is an attractive measure due to its simplicity and mathematical convenience,while similarity-based method is more accurate and robust for ECG quality assessment.

Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

Objective:To analyze the efficacies of unilateral biportal endoscopy(UBE)and percutaneous endoscopic transforaminal discectomy(PETD)in treatment of lumbar disc herniation(LDH),and to explore the optimal selection of minimally invasive surgical approaches for the The LDH patients.Methods:A retrospective analysis was performed on the clinical data of 64 LDH patients who underwent surgery at Liwan Central Hospital of Guangzhou City in Guangdong Province,between January 2020 and June 2024.The surgical approaches were determined through physician-patient communication,and the patients were divided into UBE group(n=30)and PETD group(n=34).The materials of patients were recorded including gender,age,body mass index(BMI),percentages of affected segments,course of disease,duration of hospitalization,operation duration,intraoperative blood loss,numbers of intraoperative fluoroscopy,total incision length,and time to full weight-bearing(WB).The therapeutic outcomes were evaluated using Oswestry disability index(ODI),Visual Analog Scale(VAS)scores for low back pain and leg pain,MacNab criteria,and spinal canal areas at the affected segment.the postoperative complications of the patients in two groups were analyzed.Results:There were no statistically significant differences in age,gender composition ratio,BMI,course of disease,and percentages of affected segments of the patients between UBE group and PETD group(P＞0.05).Compared with PETD group,the intraoperative blood loss,total incision length,and time to full WB of the patients in UBE group were significantly increase(P＜0.01),while the number of intraoperative fluoroscopy time was decreased(P＜0.01).Compared with pre-operation,the ODI scores and VAS scores for low back and leg pain of the patients at final follow-up in both groups were decreased(P＜0.01),and the spinal canal areas at the affected segments of the patients were increased(P＜0.01).At final follow-up,compared with PETD group,the ODI score and VAS scores for low back and leg pain of patients in UBE group were decreased(P＜0.01),while the spinal canal areas at the affected segments of the patients was increased(P＜0.01).According to MacNab criteria,the percentages of excellent and good had no significant difference between two groups(P＞0.05).The incidence of complication showed no statistical difference between two groups(P＞0.05).Conclusion:Both UBE and PETD yield satisfactory outcomes in the treatment of single-segment LDH.PETD is less invasive and permits earlier time to full WB,whereas UBE provides more extensive decompression and superior long-term efficacy.The surgical approach selection should be individualized based on specific factors in the clinic.

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.