1.Mechanisms of Huanglian Jiedutang and Its Major Active Constituents in Inhibiting LPS-induced M1 Polarisation of BV2 Microglia
Haojia ZHANG ; Kai WANG ; Kunjing LIU ; Xin LAN ; Zijin SUN ; Chunyu WANG ; Wenyuan MA ; Wei SHAO ; Jinhua HAN ; Liyang DONG ; Changxiang LI ; Xueqian WANG ; Youxiang CUI ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):44-55
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.
2.Huanglian Jiedutang Against Acute Ischemic Stroke: A Review
Liyang DONG ; Qinyuan ZHANG ; Yiping WU ; Yingping HE ; Wei SHAO ; Haojia ZHANG ; Xueqian WANG ; Changxiang LI ; Youxiang CUI ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):77-86
Huanglian Jiedutang (HLJDT), as a classical formula for clearing heat and removing toxins, has been widely applied in the treatment of various clinical diseases in recent years, particularly during the fire-heat stage of stroke, where it has attracted considerable attention. Based on previous studies, this paper systematically elaborates on the research progress on the active components of HLJDT, its clinical application in ischemic stroke, and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components, including baicalin, geniposide, and berberine. In the treatment of ischemic stroke, these components exert therapeutic effects through multi-target, multi-pathway, and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow, reduce cerebral infarct volume, and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition, the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities, promotion of angiogenesis, and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics, further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components, targets, and pathways. Combined with network pharmacology and molecular docking analyses, this study further clarifies the synergistic targets of the core components (berberine, baicalin, and geniposide), providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.
3.The evaluation value of CTP and CTA combined with serum NSE in collateral circulation status and prognosis of patients with post-stroke hemiplegia
Xin LIU ; Yu MA ; Kai LU ; Guicheng ZHANG ; Yue WU ; Fangmei HU ; Youxiang CUI ; Yunchuan SUN
Tianjin Medical Journal 2025;53(6):629-633
Objective To investigate the value of CT perfusion imaging(CTP)and CT angiography(CTA)combined with serum neuron-specific enolase(NSE)in assessing the status and prognosis of collateral circulation(CC)in hemiplegic patients with stroke.Methods A total of 106 patients with stroke hemiplegia were selected in this study.All patients underwent CTA and CTP,and patients were classified into the good CC group(n=67)and the poor CC group(n=39)based on CTA images.Patients were also classified into the good prognostic group(n=56)and the poor prognostic group(n=50)based on modified Rankin Scale(mRS)scores after 3 months of treatment.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum NSE levels.Pearson correlation analysis was used to analyse the correlation between CC scores and CTP parameters and serum NSE levels.The receiver operating characteristic(ROC)curve was used to analyze the evaluation value of serum NSE for the prognosis of hemiplegic patients after stroke.Kappa test was used to analyse the consistency of the prognosis and follow-up results of hemiplegic stroke patients assessed by CTP and CTA alone and in combination with serum NSE.Results The CTP parameters rCBF and rCBV were lower in the poor CC group than those in the good CC group(P<0.05),and levels of rTTP,rMTT and serum NSE were higher than those in the good CC group(P<0.01).CC score was positively correlated with rCBF and rCBV,and negatively correlated with rTTP,rMTT and serum NSE levels(P<0.05).The rCBF and rCBV were lower in the poor prognosis group than those in the good prognosis group,and the proportion of poor CC,rTTP,rMTT,serum NSE level and mRS score were higher than those in the good prognosis group(P<0.01).The area under the curve of serum NSE alone for predicting poor prognosis in hemiplegic patients with stroke was 0.878(95%CI:0.800-0.934),with a sensitivity of 74.00%and a specificity of 91.07%,which was in good agreement with the results of the follow-up(Kappa value=0.654,P<0.001).Conclusion CTP,CTA combined with serum NSE have a relatively high evaluation value for the assessment of the CC status and prognosis of stroke patients with hemiplegia.
4.Research progress on cell mechanics and extracellular matrix mechanics in tumor therapy
ZHANG Hui ; GAO Hui ; XIE Youxiang ; YU Dongsheng
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(10):896-907
During tumor progression, the mechanical properties of the tumor microenvironment play a pivotal regulatory role. As core mechanical indicators, cellular stiffness and extracellular matrix stiffness profoundly influence tumor development through multiple pathways, including cytoskeletal remodeling, activation of signaling pathways, and metabolic regulation. Studies have demonstrated that the tissue stiffness of various solid tumors is significantly higher than that of corresponding normal tissues, while their cellular stiffness exhibits the opposite trend. This mechanical characteristic is also observed in oral squamous cell carcinoma and exerts crucial regulatory effects during tumor progression. This review systematically summarizes the molecular composition and regulatory mechanisms underlying the stiffness of tumor cells and extracellular matrix (ECM). Mainstream stiffness detection technologies such as atomic force microscopy, microfluidic deformation, and real-time deformability cytometry are outlined, with particular emphasis on their applications and limitations in oncology research. This review comprehensively analyzes how mechanical properties regulate key processes in tumor progression, including growth, proliferation, invasion, metastasis, angiogenesis, lymphangiogenesis, drug resistance, and immune escape. This review synthesizes biomechanics-based therapeutic strategies, including: ① targeting the regulation of tumor cell stiffness through cytoskeletal modulators and cholesterol-depleting agents to enhance immune responses; ② reducing ECM stiffness by matrix remodeling enzyme inhibitors, ECM component modulators, or receptor antagonists to improve drug delivery efficiency, and combining with immunotherapy or photothermal therapy for enhanced therapeutic effects; ③ enhancing the mechanical adaptability and anti-tumor activity of immune cells through pharmacological or genetic approaches. This review establishes a robust conceptual framework for developing novel anti-tumor therapeutic strategies and provides insights for future clinical management of oral squamous cell carcinoma.
5.Clinical efficacy of isokinetic muscle strength training at different angular velocities for patients with knee hyperextension after stroke
Liangqing ZHANG ; Youxiang SHENG ; Chunzhen LI
Chinese Journal of Rehabilitation Medicine 2025;40(11):1679-1685
Objective:To observe the effects of isokinetic muscle strength training at different angular velocities on knee hyperextension in patients after stroke,and to find out better angular velocity.Method:Eighty patients with knee hyperextension after stroke were randomly divided into four groups:the control group,30°/s group,60°/s group and 90°/s group,20 cases in each group.The control group received only routine rehabilitation treatment,and the other three groups received an additional 30°/s,60°/s or 90°/s isokinetic knee flexion/extension training besides the routine treatment,respectively.Before and 3 weeks after treatment,peak torque(PT),peak torque to body weight ratio(PT/BW),average electromyographic(AEMG)and integrated electromyographic(iEMG)of the extensor and flexor knee muscles,the effective rate of knee hyperextension and lower limb Fugl-Meyer motor function score(FMA)were measured.Result:Before treatment,there was no significant difference among the four groups(P>0.05).After 3 weeks treatment,PT,PT/BW,AEMG,iEMG of the extensor and flexor knee muscles and FMA in four groups were significantly improved as compared with those before treatment(P<0.01).Moreover,the improvement of evaluation results in the 30°/s group,60°/s group and 90°/s group were higher than those in the control group(P<0.05),and those in the 30°/s group and 60°/s group were higher than those in the 90°/s group(P<0.05).However,no significant difference was found between 30°/s group and 60°/s group(P>0.05).In addition,the effective rate of knee hyperextension in the 30°/s group or 60°/s group(85%)was significantly higher than that in the control group(40%)(P<0.05),but there was no significant difference between the 90°/s group and the control group(P>0.05).Conclusion:Isokinetic muscle strength training at different angular velocities can increase the muscle strength of knee flexors and extensors,improve the control ability of knee joint,and better improve knee hyperexten-sion in patients after stroke.The lower angular velocity(≤60°/s)has a better effect.
6.The evaluation value of CTP and CTA combined with serum NSE in collateral circulation status and prognosis of patients with post-stroke hemiplegia
Xin LIU ; Yu MA ; Kai LU ; Guicheng ZHANG ; Yue WU ; Fangmei HU ; Youxiang CUI ; Yunchuan SUN
Tianjin Medical Journal 2025;53(6):629-633
Objective To investigate the value of CT perfusion imaging(CTP)and CT angiography(CTA)combined with serum neuron-specific enolase(NSE)in assessing the status and prognosis of collateral circulation(CC)in hemiplegic patients with stroke.Methods A total of 106 patients with stroke hemiplegia were selected in this study.All patients underwent CTA and CTP,and patients were classified into the good CC group(n=67)and the poor CC group(n=39)based on CTA images.Patients were also classified into the good prognostic group(n=56)and the poor prognostic group(n=50)based on modified Rankin Scale(mRS)scores after 3 months of treatment.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum NSE levels.Pearson correlation analysis was used to analyse the correlation between CC scores and CTP parameters and serum NSE levels.The receiver operating characteristic(ROC)curve was used to analyze the evaluation value of serum NSE for the prognosis of hemiplegic patients after stroke.Kappa test was used to analyse the consistency of the prognosis and follow-up results of hemiplegic stroke patients assessed by CTP and CTA alone and in combination with serum NSE.Results The CTP parameters rCBF and rCBV were lower in the poor CC group than those in the good CC group(P<0.05),and levels of rTTP,rMTT and serum NSE were higher than those in the good CC group(P<0.01).CC score was positively correlated with rCBF and rCBV,and negatively correlated with rTTP,rMTT and serum NSE levels(P<0.05).The rCBF and rCBV were lower in the poor prognosis group than those in the good prognosis group,and the proportion of poor CC,rTTP,rMTT,serum NSE level and mRS score were higher than those in the good prognosis group(P<0.01).The area under the curve of serum NSE alone for predicting poor prognosis in hemiplegic patients with stroke was 0.878(95%CI:0.800-0.934),with a sensitivity of 74.00%and a specificity of 91.07%,which was in good agreement with the results of the follow-up(Kappa value=0.654,P<0.001).Conclusion CTP,CTA combined with serum NSE have a relatively high evaluation value for the assessment of the CC status and prognosis of stroke patients with hemiplegia.
7.Clinical efficacy of isokinetic muscle strength training at different angular velocities for patients with knee hyperextension after stroke
Liangqing ZHANG ; Youxiang SHENG ; Chunzhen LI
Chinese Journal of Rehabilitation Medicine 2025;40(11):1679-1685
Objective:To observe the effects of isokinetic muscle strength training at different angular velocities on knee hyperextension in patients after stroke,and to find out better angular velocity.Method:Eighty patients with knee hyperextension after stroke were randomly divided into four groups:the control group,30°/s group,60°/s group and 90°/s group,20 cases in each group.The control group received only routine rehabilitation treatment,and the other three groups received an additional 30°/s,60°/s or 90°/s isokinetic knee flexion/extension training besides the routine treatment,respectively.Before and 3 weeks after treatment,peak torque(PT),peak torque to body weight ratio(PT/BW),average electromyographic(AEMG)and integrated electromyographic(iEMG)of the extensor and flexor knee muscles,the effective rate of knee hyperextension and lower limb Fugl-Meyer motor function score(FMA)were measured.Result:Before treatment,there was no significant difference among the four groups(P>0.05).After 3 weeks treatment,PT,PT/BW,AEMG,iEMG of the extensor and flexor knee muscles and FMA in four groups were significantly improved as compared with those before treatment(P<0.01).Moreover,the improvement of evaluation results in the 30°/s group,60°/s group and 90°/s group were higher than those in the control group(P<0.05),and those in the 30°/s group and 60°/s group were higher than those in the 90°/s group(P<0.05).However,no significant difference was found between 30°/s group and 60°/s group(P>0.05).In addition,the effective rate of knee hyperextension in the 30°/s group or 60°/s group(85%)was significantly higher than that in the control group(40%)(P<0.05),but there was no significant difference between the 90°/s group and the control group(P>0.05).Conclusion:Isokinetic muscle strength training at different angular velocities can increase the muscle strength of knee flexors and extensors,improve the control ability of knee joint,and better improve knee hyperexten-sion in patients after stroke.The lower angular velocity(≤60°/s)has a better effect.
8.Effects of gestational diabetes mellitus on brain development and miRNAs expression profile in neonatal mice
Wanyi HUANG ; Youxiang ZHANG ; Qiaoqun OU ; Yuanchun LIU ; Jiayu GUO
Chinese Journal of Child Health Care 2024;32(2):154-158
【Objective】 To study the effects of gestational diabetes (GDM) on morphological structure of brain tissue and microribonucleotide (miRNA) expression profile in neonatal mice, and to provide a new research target for the prevention and treatment of abnormal neurodevelopment in GDM progeny. 【Methods】 The pregnant mice were divided into model group and control group,each group consisted of 10 mice. The model group mice established a GDM model by injecting streptozotocin to measure fasting blood glucose (FPG) and random blood glucose (GLU) at different times. Successful molded mice were randomly divided into model group A and model group C, and control mice were divided into control group B and control group D, with 5 mice in each group. The newborn mice in groups A and B were used for hippocampal tissue GeneChip detection and brain morphology structure observation, and group C and D newborn mice were used for qRT-PCR detection of hippocampus tissue expression differences to verify the differentially expressed genes of miRANs obtained by GeneChip screening. After giving birth, the neonatal mice were sacrificed by decapitation, and the brain tissue was dissected to observe the overall morphological structure. The structural changes of hippocampus were observed under HE chromogenic microscope. The Agilent mouse miRNA oligonucleotide gene chip was used to detect the miRNA expression profile of mouse hippocampus, screen differential miRNAs and predict their target genes, and conduct GO analysis and signal transduction pathway analysis of target genes. The relative expression levels of the screened miRNAs were verified by qRT-PCR. 【Results】 Compared with the control group, the GLU increased significantly from the 3rd day after drug administration in the model group (P<0.01). Macroscopic observation of control group B mice had normal brain morphology and structure, smooth appearance, clear gyrus, close arrangement of hippocampus cell structure, uniform staining and complete structure; in model group A, the number of hippocampus cells decreased, loose arrangement and deep staining. In the initial screen of miRNA microarray, there were 11 differentially expressed miRNAs between control and model groups, all of which were downregulated miRNAs, including let-7b-5p、miR-130b-3p、miR-181c-5p、miR-181d-5p、miR-3099-3p、miR-3470a、miR-3473a、miR-3473b、miR-500-3p、miR-532-5p、miR-7047-5p(P<0.05). Two miRNAs (miR-3473b, miR-7047-75p) and 5 target genes (MAPK3, MAPK11, MAPK14, CALM3, AKT3). The relative expression of miR-3473b and miR-7047-5p in model group C were lower than that in control group D (t=19.13 and 6.24, P<0.05), and the validation results were consistent with the microarray test results. 【Conclusion】 Compared with the offspring of normal pregnant mice, GDM offspring mice have abnormal development of brain structure and damage of hippocampal nerve cells, and there are a large number of abnormal expression of miRNAs in hippocampal tissue. Differentially expressed miRNAs can be used as research targets for prevention and treatment of GDM offspring neurodevelopmental abnormalities.
9.Clinical characteristics of nasal respiratory epithelial adenomatoid hamartoma.
Ruxiang ZHANG ; Jiao XIA ; Shuhong ZHANG ; Hao TIAN ; Youxiang MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(5):338-343
〓 Objectives: To analyze the pathological and clinical features of nasal respiratory epithelial adenomatoid hamartoma(REAH), and summarize the diagnostic points, to improve the experience of diagnosis and treatment. Methods:The clinical data of 16 patients with REAH were analyzed retrospectively. The clinical manifestations, pathological features, imaging features, surgical treatment and prognosis were summarized. Results:16 cases of REAH were studied, 10 cases(62.50%) were associated with sinusitis, 1 case(6.25%) was associated with inverted papilloma, 1 case(6.25%) was associated with hemangioma. 5 cases(31.25%) had a history of nasal sinus surgery, including 1 case with 3 times of nasal sinus surgery, 1 case with 2 times of nasal sinus surgery, 3 cases with 1 time of nasal sinus surgery; 10 cases(62.50%) occurred in the bilateral olfactory cleft, 2 cases(12.50%) in the unilateral olfactory cleft, 3 cases(18.75%) in the unilateral middle turbinate, 1 case(6.25%) in the nasopharynx. All 16 patients were pathologically diagnosed as REAH. In the patients with lesions located in bilateral olfactory fissures, symmetrical widening of olfactory fissures and lateral displacement of middle turbinate were observed on preoperative sinus CT. The average width of bilateral olfactory fissures was (9.9±2.70) mm. The ratio of wide to narrow olfactory cleft was 1.21 ± 0.19. There was no significant difference in Lund-Mackay score between the two sides(P>0.05). All patients underwent surgery under general anesthesia and nasal endoscopy. The follow-up period ranged from 1 to 66 months, and no recurrence occurred. Conclusion:Preoperative diagnosis of REAH is facilitated by the combination of clinical manifestations and endoscopic and imaging features. Endoscopic complete resection can achieve a good therapeutic effect.
Humans
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Nasal Polyps/complications*
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Retrospective Studies
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Paranasal Sinuses/pathology*
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Adenoma
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Endoscopy/methods*
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Hamartoma/surgery*
10.Case report of infant perianal necrotizing fasciitis
Shuzhe XIAO ; Sirong LIU ; Zhihong HAO ; Xinzhou RONG ; Youxiang ZHANG
Chinese Journal of Applied Clinical Pediatrics 2021;36(5):385-386
The clinical data of a child with perianal necrotizing fasciitis admitted to the Department of Pedia-trics of Guangzhou First People′s Hospital were retrospectively analyzed.The child, girl, more than 5 months old, the clinical features of the onset of fever and diarrhea, only 10 days after the onset, the child′s skin progressed from redness and swelling to perianal skin and soft tissue ulcers, fat liquefaction, visible rectum exposure.After surgical incision, thorough debridement and drainage and selection of sensitive antibiotics, the child recovered and was discharged.Perianal necrotizing fasciitis is a rare necrotizing soft tissue infection caused by a variety of bacterial infections.Because its early performance is difficult to distinguish, the symptoms are serious, and the mortality rate is high.It should been pain attention in clinical work.


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