1.Research progress on non-surgical treatment of intermittent exotropia
International Eye Science 2026;26(1):91-95
Intermittent exotropia(IXT)is the most prevalent form of childhood strabismus, with an estimated prevalence of approximately 3.26% in the Chinese population. Although patients can intermittently maintain orthotropia, the deviation angle often fluctuates markedly, and frank exotropia may become evident during fatigue or lapses in attention. Without intervention, roughly 75% of cases progress over time. Management comprises surgical and non-surgical approaches. Surgery remains the most definitive treatment, however, the optimal timing is controversial, and postoperative outcomes may include under- or over-correction, necessitating additional procedures. Non-surgical options include observation, refractive correction, over-minus lens therapy, prisms, orthoptic exercises, and botulinum toxin-A injections. These modalities are particularly suitable for young, or uncooperative children, patients with small-angle, well-controlled deviations, or those seeking to defer surgery, in such cases, non-surgical treatment can maintain binocular alignment and preserve monocular function, thereby delaying or avoiding surgery. Because the efficacy of each non-surgical strategy varies, this review summarizes the current evidence on non-surgical treatment of IXT.
2.Multicenter machine learning-based construction of a model for predicting potential organ donors and validation with decision curve analysis
Xu WANG ; Wenxiu LI ; Fenghua WANG ; Shuli WU ; Dong JIA ; Xin GE ; Zhihua SHAN ; Tongzuo LI
Organ Transplantation 2026;17(1):106-115
Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.
3.Improvement effects and mechanism of astragaloside Ⅳ on neuroinflammation
Mimi WANG ; Yonggang FENG ; Yun HAN ; Kaixin SHAN ; Fuyu LIU ; Mingsan MIAO ; Xiaoyan FANG
China Pharmacy 2026;37(1):30-35
OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ (AS- Ⅳ ) on lipopolysaccharide (LPS)-induced neuroinflammation. METHODS BV2 cells were divided into control group, LPS group, AS-Ⅳ groups at concentrations of 20 and 40 μmol/L, and dexamethasone group (2 μmol/L). Except for control group, neuroinflammation model was established with LPS (1 μg/mL) in other groups after medication. The levels of inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO)] in cell supernatant were measured in each group. Mice were randomly divided into normal group, model group, positive control group (Aspirin enteric-coated tablet, 20 mg/kg), AS-Ⅳ low- and high-dose groups (10, 20 mg/kg), with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection, once a day, for 14 consecutive days. Except for normal group, other groups were intraperitoneally injected with LPS (250 μg/kg) 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication; histopathological morphology of cerebral tissue in mice were observed; the co-localization of inducible nitric oxide synthase (iNOS)/ionized calcium binding adapter molecule 1 (Iba1) and CD206/Iba1 in the cerebral cortex region of mice was observed; the expressions of proteins related to the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway in brain tissue of mice were also determined, including NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), extracellular signal-regulated kinase (ERK), and phosphorylated ERK (p-ERK). RESULTS In the cell experiments, compared with control group, the levels of IL-6, TNF- α and NO in the cell supernatant of the LPS group were increased significantly (P<0.05); compared with LPS group, the levels of IL-6, TNF-α and NO were decreased significantly in the administration groups (P<0.05). In the animal experiments, compared with the normal group, the serum levels of IL-6 and TNF- α, the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex, and the phosphorylation levels of p38 MAPK, NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group (P<0.05); the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased (P<0.05). The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group, above quantitative indexes of mice were all reversed significantly in administration groups (P<0.05); the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway, promote the M2-type polarization of microglia, and thereby suppress neuroinflammatory responses.
4.Comparison of Wild and Cultivated Bupleurum scorzonerifolium Based on Traditional Quality Evaluation
Changsheng YUAN ; Feng ZHOU ; Xingyu LIU ; Yu SHI ; Yihan WANG ; Huaizhu LI ; Yongliang LI ; Shan GUAN ; Huaizhong GAO ; Yanmeng LIU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):203-214
ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots(BSR), and explore the underlying molecular mechanisms, providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin(YLW) served as the quality reference, we conducted comparative analysis among YLW, locally domesticated wild germplasm in Yulin(YLC3), Daqing germplasm introduced and cultivated in Yulin(YLDQC3), and locally cultivated germplasm in Daqing(DQC3). A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed, including macroscopic traits(appearance, odor), microscopic features(proportions of cork, phloem, xylem), cell wall component contents(hemicellulose, cellulose, lignin), carbohydrate contents(starch, water-soluble polysaccharides), marker compound contents(ethanol-soluble extracts, total saponins, liposoluble extracts, and saikosaponins A, B2, C, D), metabolomics, and transcriptomics, in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically, Yulin-produced BSR(YLW, YLC3, YLDQC3) exhibited significantly greater weight, length, and upper and middle diameters than Daqing-produced BSR(DQC3). Odor-wise, YLW and YLC3 had a a fragrance taste, YLDQC3 had a rancid oil odor, and DQC3 had a sweet and fragrant taste. Microscopically, Yulin germplasm(YLW, YLC3) and Daqing germplasm(YLDQC3, DQC3) shared similar structural features, respectively. However, Yulin germplasm showed significantly higher proportions of cork and phloem, as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents, Yulin germplasm contained significantly higher levels of ethanol-soluble extracts, total saponins, and saikosaponins A, B2, C, D, while Daqing germplasm had significantly higher levels of hemicellulose, starch, and liposoluble extracts. After introduction to Yulin, the Daqing germplasm(YLDQC3) showed increased starch, water-soluble polysaccharides and liposoluble extracts contents, decreased cell wall component content, but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm, while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway, including one acetyl-coenzyme A(CoA) acetyltransferase gene(ACAT), one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene(HMGS), two hydroxymethylglutaryl-CoA(HMG-CoA) reductase genes(HMG), one phosphomevalonate kinase gene(PMK), one 1-deoxy-D-xylose-5-phosphate synthase gene(CLA), one hydroxymethylbuten-1-aldol synthase gene(HDR), two farnesyl pyrophosphate synthase genes(FPPS), one squalene synthase gene(SQS), one β-amyrin synthase gene(BAS), 102 cytochrome P450(CYP450) gene family members, and 32 uridine diphosphate-glucuronosyltransferase(UGT) gene family members. ConclusionAmong the three cultivated types, YLC3 most closely resembles YLW in appearance, microscopic features, contents of major bioactive constituents, metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm, and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings, it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.
5.Comparison of Wild and Cultivated Polygalae Radix Based on Traditional Quality Evaluation
Yihan WANG ; Yanmeng LIU ; Huaizhu LI ; Yongliang LI ; Shan GUAN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):215-224
ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties, this paper systematically contrasted the quality differences between wild Polygalae Radix(WPR) and cultivated Polygalae Radix(CPR) from the aspects of character, microscope and chemical composition by modern scientific and technological means, providing a basis for high-quality production and quality control. MethodsCPR and local WPR in Yulin city, Shaanxi province from 1 to 6 years were collected, and a systematic comparative analysis was conducted using traditional pharmacognosy research methods combined with modern multi-omics analysis techniques, including character traits(length, weight, diameter), cross-sectional microscopic features(proportions of cork, phloem, xylem, etc), cell wall component content(hemicellulose, cellulose, lignin), extracts content(water-soluble extract and alcohol-soluble extract), carbohydrate content(starch, water-soluble polysaccharides), contents of total flavonoids, total saponins and specific marker compounds(3,6′-disinapoyl sucrose, polygalaxanthone Ⅲ, tenuifoliside A, tenuifoliside C, sibiricose A5 and A6) and other indexes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to conduct comparative analysis of secondary metabolites in WPR and CPR, and multivariate statistical analysis such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined to screen the key differential components of them. ResultsIn terms of appearance, there were significant differences between WPR and CPR. The characteristics of WPR conformed to the "thick wrinkles on the epidermis" recorded in ancient books, featuring a wrinkled surface and grayish-brown appearance. However, CPR had a finer texture and a yellowish white appearance, with weight, length, and diameter increasing with longer cultivation periods. In terms of microscopy, WPR exhibited a thick cork layer with fissures in the phloem, whereas CPR had a thinner cork layer with uniformly arranged cork cells. Younger PR specimens showed numerous phloem fissures in cross-sections, while older specimens display progressively denser arrangements of phloem parenchyma cells. In terms of the contents of various major components, the contents of water-soluble extract, starch and total saponins in WPR were inversely proportional to the root diameter, while the contents of water-soluble extract, water-soluble polysaccharides and total saponins in CPR decreased with the increase of planting years. The content of xanthones in WPR was significantly higher than that of CPR, while the contents of other major components showed no significant change pattern. Among the six indicator components, the average content of sibiricose A5 in WPR was significantly higher than that of CPR, followed by slightly higher content of tenuifoliside A. In CPR, the relative content of 3,6′-disinapoyl sucrose and tenuifoliside A was the highest. The former showed an increase in volatility with increasing cultivation years, while the latter showed a decrease in volatility. The results of differential compound analysis based on UPLC-Q-TOF-MS showed that there were significant differences in metabolites between WPR and CPR samples. Among them, the seven compounds with the largest differences among WPR samples of different thicknesses were polygalasaponins, and for CPR with different planting years, the main differential compounds were oligosaccharide esters. ConclusionThere are differences between WPR and CPR in character, microscopic structure and chemical composition, and some components are inversely proportional with the increase of diameter and cultivation duration due to the distribution characteristics. However, the longer the cultivation years of PR, the closer it is to the "thick wrinkles on the epidermis" of WPR, which has been respected by generations. It is suggested that this traditional character combined with modern component contents should be used as the index of artificial cultivation and quality control of PR.
6.Research progress of non-insulin hypoglycemic drugs in the treatment of type 1 diabetes mellitus
Zejie XU ; Jiaoni ZHENG ; Jing LUO ; Liangyu WANG ; Wei YAN ; Qiang HE ; Xuefeng SHAN
China Pharmacy 2026;37(2):263-267
Traditional treatment for type 1 diabetes mellitus (T1DM) primarily involves insulin replacement, yet some patients encounter issues such as significant blood glucose fluctuations, high risk of hypoglycemia, and weight gain. In recent years, the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM: amylin analogues (pramlintide), biguanides (metformin), sodium-glucose co-transporter 2 inhibitor, dipeptidyl peptidase-4 inhibitor, and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity, delaying gastric emptying, promoting urinary glucose excretion, and regulating incretin levels, thereby reducing glycated hemoglobin levels, decreasing insulin dosage, and managing body weight. Simultaneously, these drugs also present limitations such as low patient compliance due to complex dosing regimens, increased risk of diabetic ketoacidosis, and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies, combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit, and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.
7.BANCR/miR-145-5p-Reg3A/DMBT1 Axis Facilitates AKT-GLUT1/HK2-Mediated Warburg Effect in Gastric Cancer
Liang WANG ; Yufei LIANG ; Yan ZHAO ; Shan LIN
Cancer Research on Prevention and Treatment 2026;53(2):112-120
Objective To elucidate the mechanism by which the BANCR/miR-145-5p axis regulates the AKT-GLUT1/HK2 pathway through downstream targets Reg3A/DMBT1 to facilitate the Warburg effect in gastric cancer. Methods Expression levels of BANCR, miR-145-5p, Reg3A, and DMBT1 were detected by RT-qPCR and Western blot in gastric cancer tissues and cell lines. Dual-luciferase reporter assays confirmed targeted relationships. Glycolytic capacity was assessed via glucose uptake. Immunohistochemistry analyzed molecular expression in 60 paired clinical samples. The prognostic values of key molecules in the BANCR/miR-145-5p-Reg3A/DMBT1 axis were evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression model. Results BANCR was significantly upregulated, whereas miR-145-5p was downregulated in gastric cancer tissues, correlating with advanced TNM stage, lymph node metastasis, and poor differentiation. Reg3A and DMBT1 were identified as direct targets of miR-145-5p. Knockdown of BANCR or overexpression of miR-145-5p significantly suppressed Reg3A/DMBT1 expression, reduced AKT phosphorylation and GLUT1/HK2 levels, and inhibited glycolysis. Clinical analysis revealed positive correlations between Reg3A/DMBT1 expression and glycolytic markers, with both serving as independent risk factors for poor prognosis. Conclusion The BANCR/miR-145-5p axis activates the AKT pathway by targeting Reg3A/DMBT1, thereby promoting GLUT1/HK2/LDHA-mediated glycolysis and facilitating the Warburg effect in gastric cancer. This regulatory axis represents a potential therapeutic target and prognostic biomarker.
8.Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression
Zijin SUN ; Kai WANG ; Haojia ZHANG ; Linjing SONG ; Zhaoyi WANG ; Wenxiu XU ; Jing JI ; Yonglin SHAN ; Qianqian SHI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):54-63
ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion (MCAO) and to explore its mechanism of action on oligodendrocytes, particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow, 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure infarct volume, and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group (n=24), model group (n=24), Huanglian Jiedutang group (n=24), and Ginkgo biloba extract (GBE) group (n=18). After 1 week of acclimatization, intragastric administration was initiated. The sham and model groups received normal saline, the Huanglian Jiedutang group was administered 1.82 g·kg-1, and the GBE group was administered 0.432 g·kg-1 after preparation as a 2.16 g·L-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·(10 g)-¹·d-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection (UMAP) dimensionality reduction and unsupervised clustering, and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally, real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group, the model group showed significantly increased neurological function scores (P<0.01), significantly impaired blood flow (P<0.01), significantly enlarged cerebral infarct area (P<0.01), and pathological changes including disordered cortical structural arrangement, aggravated cytoplasmic vacuolization, and increased Nissl bodies. Compared with the model group, the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores (P<0.01), markedly restored blood flow levels (P<0.01), significantly reduced cerebral infarct area (P<0.01), and improvement in cortical structural disorder, alleviation of cytoplasmic vacuolization, and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte (Mye-OL) subpopulation existed among oligodendrocytes, which was closely related to myelin generation. Compared with the sham group, the number of Mye-OL cells decreased in the model group. Compared with the model group, the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes, including MOG, MBP, and MAG, via transcription factors such as OLIG1, OLIG2, NKX2-2, and SOX10, thereby regulating myelin generation, restoring cognition, and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group, the mRNA expression levels of OLIG1, OLIG2, NKX2-2, and SOX10 were significantly downregulated in the model group (P<0.01), and the mRNA expression levels of myelin-related genes, including MOG, MBP, and MAG, were also significantly downregulated (P<0.01). In contrast, compared with the model group, the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1, OLIG2, NKX2-2, and SOX10 (P<0.01), and significantly upregulated mRNA expression levels of myelin-related genes, including MOG, MBP, and MAG (P<0.01). ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.
9.Observation of short-term efficacy of autologous serum eye drops combined with prednisolone acetate for severe dry eye with grade II-III corneal injury
Jie XIAO ; Yuan TU ; Shan WANG
International Eye Science 2026;26(4):587-593
AIM:To investigate the short-term efficacy of autologous serum eye drops combined with prednisolone acetate in the treatment of severe dry eye with grade II-III corneal injury.METHODS:Prospective, randomized, controlled single center study. Totally 122 patients(122 eyes, all enrolled patients had bilateral disease, with the more severely affected eye selected as the study eye; if the severity was similar between both eyes, the right eye was chosen as the study eye)with severe dry eye and grade II-III corneal injury who were treated at Wuhan University Affiliated Aier Eye Hospital from March 2023 to March 2025 were randomly divided into a control group(treated with sodium hyaluronate eye drops combined with autologous serum eye drops)and an observation group(treated with sodium hyaluronate eye drops, autologous serum eye drops combined with prednisolone acetate eye drops)using a random number table method. After continuous administration for 2 wk, the tear inflammatory reaction [interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)], subjective symptoms [ocular surface disease index(OSDI)score], lacrimal gland function [tear film break-up time(TBUT)and Schirmer tear secretion test(SⅠt)], corneal injury degree [corneal fluorescein staining(CFS)score] and corneal nerve function [total number and density of corneal subepithelial nerve(SBN)] before and after treatment were compared between the two groups, and the occurrence of adverse reactions during treatment was recorded. RESULTS:All patients have completed follow-up. The control group consisted of 61 cases and 61 eyes, with 24 males and 37 females, with an average age of 43.87±5.12y. There were 61 cases and 61 eyes in the observation group, including 21 males and 40 females, with an average age of 42.15±4.76y. At 1 and 2 wk after treatment, the levels of IL-6 and TNF-α in tears, OSDI score, and CFS score of the two groups were significantly lower than those before treatment, and those in the observation group were lower than those in the control group(all P<0.05). The total number of TBUT, SⅠt, SBN, and SBN density in both groups of patients increased significantly compared to before treatment, and the observation group was higher than the control group(all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups of patients during treatment(P=0.717).CONCLUSION:The combination of autologous serum eye drops and prednisolone acetate is effective in treating severe dry eye with grade II-III corneal injury. It can reduce patients' inflammatory reactions, subjective symptoms, and degree of corneal injury, promote the improvement of lacrimal gland function and corneal nerve function, providing a new strategy for corneal nerve repair. Furthermore, the combination therapy does not increase the risk of adverse reactions and shows good safety in short-term application.
10.Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression
Zijin SUN ; Kai WANG ; Haojia ZHANG ; Linjing SONG ; Zhaoyi WANG ; Wenxiu XU ; Jing JI ; Yonglin SHAN ; Qianqian SHI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):54-63
ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion (MCAO) and to explore its mechanism of action on oligodendrocytes, particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow, 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure infarct volume, and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group (n=24), model group (n=24), Huanglian Jiedutang group (n=24), and Ginkgo biloba extract (GBE) group (n=18). After 1 week of acclimatization, intragastric administration was initiated. The sham and model groups received normal saline, the Huanglian Jiedutang group was administered 1.82 g·kg-1, and the GBE group was administered 0.432 g·kg-1 after preparation as a 2.16 g·L-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·(10 g)-¹·d-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection (UMAP) dimensionality reduction and unsupervised clustering, and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally, real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group, the model group showed significantly increased neurological function scores (P<0.01), significantly impaired blood flow (P<0.01), significantly enlarged cerebral infarct area (P<0.01), and pathological changes including disordered cortical structural arrangement, aggravated cytoplasmic vacuolization, and increased Nissl bodies. Compared with the model group, the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores (P<0.01), markedly restored blood flow levels (P<0.01), significantly reduced cerebral infarct area (P<0.01), and improvement in cortical structural disorder, alleviation of cytoplasmic vacuolization, and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte (Mye-OL) subpopulation existed among oligodendrocytes, which was closely related to myelin generation. Compared with the sham group, the number of Mye-OL cells decreased in the model group. Compared with the model group, the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes, including MOG, MBP, and MAG, via transcription factors such as OLIG1, OLIG2, NKX2-2, and SOX10, thereby regulating myelin generation, restoring cognition, and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group, the mRNA expression levels of OLIG1, OLIG2, NKX2-2, and SOX10 were significantly downregulated in the model group (P<0.01), and the mRNA expression levels of myelin-related genes, including MOG, MBP, and MAG, were also significantly downregulated (P<0.01). In contrast, compared with the model group, the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1, OLIG2, NKX2-2, and SOX10 (P<0.01), and significantly upregulated mRNA expression levels of myelin-related genes, including MOG, MBP, and MAG (P<0.01). ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

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