ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 （CDK4）-early 2 factor （E2F） signaling pathway. MethodsFor the cell experiment， 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group （administrated with an equal volume of 0.9% sodium chloride injection） and a Qiangjing tablets group （20 rats in each group） according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L^-1 H₂O₂， and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC （1 mmol·L^-1） was used as the positive control for eliminating reactive oxygen species （ROS）. Cells were intervened with Qiangjing tablets-containing serum at low （2.5%）， medium （5%）， and high （10%） concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）， and the protein levels of CDK4， E2F1， and E2F2 were analyzed by Western blot. In the animal experiment， 19-month-old naturally aging rats were used as the model group， and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg^-1·d^-1 testosterone propionate. Qiangjing tablets were administered by gavage at low， medium， and high doses of 0.72， 1.44， 2.88 g·kg^-1·d^-1， respectively. The general conditions of rats were observed， and the protein levels of CDK4， E2F1， and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment， compared with the blank control group， the model group showed upregulated expression of CDK4 and E2F1 （P<0.05） and slightly downregulated expression of E2F2. Compared with that in the model group， the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group （P<0.05）， slightly upregulated in the medium-dose Qiangjing tablets group， and downregulated in the high-dose Qiangjing tablets group （P<0.05）. The NAC group showed downregulated expression of E2F1 （P<0.05） and E2F2， and the low-， medium-， and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 （P<0.05）. Compared with that in the NAC group， the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose （P<0.05） groups. The expression of E2F1 was down-regulated in all the three dose groups， with statistically significance in the high dose group （P<0.05）， and that of E2F2 were downregulated in all the three dose groups （P<0.05）. In the animal experiment， compared with the young control group， the model group exhibited downregulated expression of CDK4 （P<0.05） and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group， the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group （P<0.05） but increased in the medium-dose （P<0.05） and high-dose groups. In addition， the expression of E2F1 decreased （P<0.05）， and that of E2F2 was slightly elevated. Compared with that in the NAC group， CDK4 expression was elevated in the Qiangjing tablets groups， with statistical significance in the medium- and high-dose groups （P<0.05）. Similarly， the E2F1 expression was also upregulated in the Qiangjing tablets groups， with statistical significance in the medium-dose group （P<0.05）. The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.

LIU Wansu， as the foremost of the four great masters of the Jin-Yuan period， established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke， thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background， academic origins， and core connotations of its theoretical construction. The study found that， based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic （Huang Di Nei Jing） and combined with clinical practice， LIU Wansu proposed that fire-heat is the fundamental cause of stroke， and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire， emphasizing differentiated treatment of exterior and interior syndromes， Six Meridians syndrome differentiation， and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period， but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi， thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine （TCM）. Modern pharmacological research provides solid scientific evidence， confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses， oxidative stress， and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents， such as Huanglian Jiedu Tang and baicalin， can exert multi-target neuroprotective effects by regulating inflammatory signaling， enhancing antioxidant enzyme activity， and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis， and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.

LIU Wansu， as the foremost of the four great masters of the Jin-Yuan period， established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke， thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background， academic origins， and core connotations of its theoretical construction. The study found that， based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic （Huang Di Nei Jing） and combined with clinical practice， LIU Wansu proposed that fire-heat is the fundamental cause of stroke， and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire， emphasizing differentiated treatment of exterior and interior syndromes， Six Meridians syndrome differentiation， and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period， but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi， thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine （TCM）. Modern pharmacological research provides solid scientific evidence， confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses， oxidative stress， and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents， such as Huanglian Jiedu Tang and baicalin， can exert multi-target neuroprotective effects by regulating inflammatory signaling， enhancing antioxidant enzyme activity， and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis， and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Haloacetic acids(HAAs),as a class of disinfection byproducts in drinking water,pose potential threats to human health,so the rapid,accurate and simultaneous detection of HAAs is of great significance for ensuring drinking water safety.Aiming at the challenges in HAAs detection and risk analysis,a novel method for synchronous rapid detection of seven kinds of HAAs in drinking water based on in situ derivatization technology and headspace gas chromatography was developed in this study.Through single-factor optimization experiments,the optimal reaction parameters for in situ derivatization were determined,including the type and dosage of salting-out agent,the acidity of reaction system,the amount of phase transfer catalyst,the dosage of derivatization agent,and the extraction solvent volume.Methodologic validation showed that the seven kinds of HAAs exhibited excellent linear relationships within their respective detection concentration ranges(R2>0.998).The method detection limits(MDLs)ranged from 0.04 to 0.33 μg/L,and the limits of quantification(LOQs)were between 0.14 and 1.34 μg/L.For real water samples,the average spiked recoveries of the seven HAAs ranged from 90.9%to 107.7%,with relative standard deviation(RSDs)between 1.55%and 6.49%,and the HAAs contents in all tested samples were below the limits specified in the Standards for Drinking Water Quality(GB 5749-2022)of China.This method was featured with simple operation,fast analysis speed,high sensitivity,and good accuracy,providing an efficient and reliable technical support for routine monitoring of HAAs contaminants in drinking water and showing promising application value for widespread promotion.

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

Objective:To investigate the clinicopathological features, immunophenotype and molecule characteristics of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue.Methods:The clinical and pathological data of 2 cases of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue diagnosed at the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China from May 2023 to May 2024 were analyzed. Immunohistochemical study, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) were performed. Relevant literature was reviewed.Results:There were one male and one female patients, aged 35 and 29 years, respectively. The tumors developed in the somatic soft tissue, including calf and chest wall, and were 6.0 and 6.2 cm in size, respectively. The imaging studies suggested space-occupying lesions in muscle tissue. Case 1 did not involve the bone, while Case 2 showed fracture of the 8th rib. Microscopically, a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. The tumors were composed of small to medium-sized round and short spindle-shaped cells, showing nodular or sheet-like pattern. The tumor cells showed round nuclear outline, coarse chromatin with prominent nucleoli. Immunohistochemically, tumor cells showed diffuse positivity of ALK (D5F3), MUM1 and Syn, focal or patchy positivity of CKpan, EMA, S-100, NSE, WT-1 and SMA, and a high Ki-67 index (20%-30%). FISH demonstrated break-apart signals of EWSR1 gene in the 2 cases. NGS revealed EWSR1::CREM gene fusion. Case 2 showed an ATRX gene mutation. The two patients were free of recurrence or metastasis at the 10-month and 1-month follow-up, respectively.Conclusions:EWSR1::CREM fusion malignant epithelioid neoplasm is rare and lacks distinctive morphological and immunohistochemical features. FISH and NGS can help make a definitive diagnosis.

OBJECTIVES: This study aims to analyze the biomechanics of three kinds of rigid internal fixation methods for condylar head fractures. METHODS: A three dimensional finite element model of the normal mandible was constructed. It was then used to prepare condylar head fracture finite element model and three kinds of rigid internal fixation finite element model (unilateral tension screw, bilateral tension screw, tension screw+titanium plate). The mechanical characteristics and changes of the mandible condyle under the same mechanical conditions were compared among the three different rigid internal fixation methods. RESULTS: The maximum equivalent stress and displacement of the non-free end of condyle under the rigid internal fixation method of unilateral tension screw were 71.03 MPa and 4.72 mm, respectively. The maximum equivalent stress and displacement of the free end of condyle were 78.45 MPa and 4.50 mm, respectively. The maximum stress of fracture suture was 3.27 MPa. The maximum equivalent stress and displacement of the non-free end of condyle under the rigid internal fixation method of bilateral tension screw were 70.52 MPa and 4.00 mm, respectively. The maximum equivalent stress and displacement of the free end of condyle were 72.49 MPa and 3.85 mm, respectively. The maximum stress of fracture suture was 2.33 MPa. The maximum equivalent stress and maximum displacement of the non-free end of condyle under the rigid internal fixation method of tension screw+titanium plate were 67.26 MPa and 2.66 mm, respectively. The maximum equivalent stress and maximum displacement of the free end of condyle were 69.66 MPa and 2.50 mm, respectively. The maximum stress of fracture suture was 2.18 MPa. CONCLUSIONS The tension screw+titanium plate rigid internal fixation method is the most conducive to biomechanical distribution for condylar head fractures.
Fracture Fixation, Internal/instrumentation* ; Mandibular Condyle/surgery* ; Biomechanical Phenomena ; Bone Screws ; Finite Element Analysis ; Humans ; Mandibular Fractures/surgery* ; Bone Plates ; Titanium ; Stress, Mechanical

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective:To develop and validate CT radiomics models based on machine learning for predicting recurrence of chronic subdural hematoma (cSDH) after endoscopic treatment.Methods:A retrospective study was performed; 252 patients with cSDH who underwent endoscopic treatment in Department of Neurosurgery, the Second Affiliated Hospital of Soochow University from October 2016 to October 2024 were selected. The clinical and imaging data of these patients were collected, and these patients were divided into a training set ( n=176) and a validation set ( n=76) at a ratio of 7:3. Patients in both sets were further sub-divided into a recurrence group and a non-recurrence group based on whether they had recurrence within 3 months of discharge. (1) Radiomics features of cSDH on initial non-enhanced CT images were extracted using 3D-Slicer software. Optimal features were selected through univariate analysis and least absolute shrinkage and selection operator (LASSO) regression analysis; based on these optimal features, 3 machine learning algorithms (Logistic, support vector machine [SVM], and K-nearest neighbor [KNN]) were used to construct CT radiomics models. Differences in predictive performance of different radiomics models were compared by analyzing indicators such as sensitivity, specificity, and area under receiver operating characteristic (ROC) curve (AUC), and the best model was selected. (2) Based on the initial non-enhanced CT images, cSDH was classified into homogeneous type, laminar type, septated type, and trabecular type according to Nakaguchi classification system; combined these cSDH typing with clinical features (clinical Markwalder's grade and bilateral hematoma), univariate analysis and multivariate Logistic regression analysis were used to screen the independent risk factors for cSDH recurrence. Based on these factors, the 3 machine learning algorithms (Logistic, SVM, KNN) were used to construct hematoma typing-clinical feature models; differences in predictive performance of different hematoma typing-clinical feature models were compared by analyzing indicators such as sensitivity, specificity, and AUC, and the best model was selected. (3) DeLong's test was used to compare the ROC curve differences between the CT radiomics model and hematoma typing-clinical feature model. Decision curve analysis was used to compare the effective scope of the CT radiomics model and hematoma typing-clinical feature model. Results:(1) Seven optimal CT radiomics features based on wavelet transform were obtained after univariate analysis and LASSO regression: one gray-level dependence matrix feature, one first-order energy feature, two gray-level co-occurrence matrix features, two gray level size zone matrix features, and one gray-level run-length matrix feature. The KNN model constructed based on these 7 optimal features had the best performance in predicting cSDH recurrence, with an AUC of 0.845, a sensitivity of 0.833, a specificity of 0.857, a recall rate of 0.833, and an F1 score of 0.476 in patients from the validation set. (2) Three independent risk factors for cSDH recurrence were screened out through univariate analysis and multivariate Logistic regression analysis: hematoma Nakaguchi classification, Markwalder's grade, and bilateral hematoma. Logistic model constructed based on these 3 factors had the best performance in predicting cSDH recurrence, with an AUC of 0.675, a sensitivity of 0.609, a specificity of 0.654, a recall rate of 0.609, and an F1 score of 0.311 in patients from the validation set. (3) DeLong's test showed that the AUC of the CT radiomics model was significantly greater than that of the hematoma typing-clinical feature model in patients from the training set and validation set ( P=0.027 and P=0.035). Decision curve analysis showed that in the CT radiomics model, the net benefit of the model was >0 when the risk threshold was 0.05-0.95; in the hematoma typing-clinical feature model, the net benefit of the model was >0 when the risk threshold was 0.05-0.55. Conclusion:The KNN model based on 7 CT radiomics features in this study can effectively predict the cSDH recurrence in patients after endoscopic treatment, and its performance is obviously better than that of hematoma typing-clinical feature model constructed in this study.