1.Efficacy comparison of foldable capsular body with scleral buckling in treating experimental retinal detachment
Yifan DONG ; Baike ZHANG ; Yong JIA ; Fan YANG ; Lisha GUO ; Xiangyang ZHANG ; Cong LU ; Zhonghao ZHANG ; Haiyan WU ; Xuemin TIAN
International Eye Science 2025;25(10):1566-1573
AIM: To compare the effectiveness of foldable capsular body(FCB)with traditional scleral buckling(SB)in the treatment of experimental retinal detachment animal models.METHODS: After successfully establishing rhegmatogenous retinal detachment(RRD)animal models, 24 New Zealand white rabbits were randomly divided into three groups(RRD models group, SB group, and FCB group), with 8 rabbits in each group. The FCB and SB groups underwent SB and FCB surgeries for the RRD animal models, while the RRD models group only consists of RRD models without any surgical intervention during the follow-up period. The follow-up duration was 3 mo. Wide-field neonatal fundus imaging system and ophthalmic B-ultrasound were used to assess the fundus conditions before and after surgery. The Icare® TONOVET Plus tonometer was utilized to evaluate intraocular pressure changes before and after surgery. The Eaton and Draize scoring systems were selected to monitor postoperative inflammatory reactions.RESULTS: The retinal reattachment rates in the FCB and SB groups were 87.5% and 75.0%, respectively, with no statistically significant difference between the groups(P>0.05). The intraocular pressure in both the FCB and SB groups increased postoperatively compared to preoperative levels(P<0.01), and there were no significant differences in intraocular pressure at any time points during the follow-up period between the groups(P>0.05). The intraocular pressure in the RRD models group remained at a low level throughout the follow-up period. The average surgical time for the FCB group was 16.87±2.29 min, which was shorter than 46.25±4.74 min in the SB group(t=-15.166, P<0.001). According to the Eaton and Draize scoring systems, the FCB group had lower grades of conjunctival hyperemia and edema in the early postoperative period compared to the SB group, indicating milder inflammatory reactions(P<0.05).CONCLUSION: Both FCB and SB are effective in treating experimental RRD. Compared to SB, FCB is simpler to operate, and also has a shorter surgical time and milder postoperative inflammatory reactions.
2.Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131-TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells.
Yuquan TAO ; Yinuo MA ; Limei GU ; Ye ZHANG ; Qinchang ZHANG ; Lisha ZHOU ; Jie PAN ; Meng SHEN ; Xuefei ZHUANG ; Linmei PAN ; Weixing SHEN ; Chengtao YU ; Dan DONG ; Dong ZHANG ; Tingsheng LING ; Yang SUN ; Haibo CHENG
Acta Pharmaceutica Sinica B 2025;15(7):3545-3560
Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc Min/+ mice and clinical patients. There was a marked accumulation of CCL22+ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22+ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22+ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.
3.Tertiary lymphoid structures: The touchstone for tumor immunotherapy.
Lisha ZHOU ; Shunji LIU ; Yang SUN
Acta Pharmaceutica Sinica B 2025;15(11):6070-6072
4.Establishment of HPLC fingerprint and content determination of Gerbera delavayi
Lisha SUN ; Li JIANG ; Li LI ; Lin TIAN ; Yang WANG ; Jie PAN ; Yueting LI ; Yongjun LI
China Pharmacy 2025;36(9):1052-1058
OBJECTIVE To establish the fingerprint of Gerbera delavayi and the methods for the content determination of 11 components in G. delavayi. METHODS High-performance liquid chromatography(HPLC)was adopted to establish the fingerprints of 13 batches of G. delavayi(No. S1-S13), and the similarities were evaluated according to Similarity Evaluation System of Chromatographic Fingerprint of TCM (2012 edition), while the common peaks were identified. Hierarchical clustering analysis (HCA), principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were carried out by using SPSS 25.0 software and SIMCA 14.1 software. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 3,8-dihydroxy-4-methoxy-2-oxo-2H-1-benzopyran-5-carboxylic acid, caffeic acid, 3-hydroxy-4-methoxy-2- oxo-2H-1-benzopyran- 5-carboxylic acid, luteolin-7-O-β-D-glucoside, isochlorogenic acid A, apigenin-7-O-β-D-glucoside, isochlorogenic acid C and xanthotoxin were determined by HPLC. RESULTS The similarities in HPLC fingerprint of 13 batches of G. delavayi were 0.801-0.994; a total of 38 common peaks were identified and 13 common peaks were identified. The results of HCA showed that S1-S5 and S7 were clustered into one group, S6 into one category, S8 into one category, S9 and S11 into one category, S10, S12 and S13 into one category, and the results of PCA were consistent with them. The results of OPLS-DA showed that variable importance values for the projection of peak 7 (chlorogenic acid), peak 21 (isochlorogenic acid A), peak 26 (xanthotoxin), peak 19 (isochlorogenic acid B), peak 33, peak 13, peak 23 (isochlorogenic acid C), peak 2 (new chlorogenic acid), peak 17 (luteolin-7-O-β-D- glucoside) were greater than 1. The above 11 components had good linearity in their respective detection concentration ranges (r was greater than 0.999). RSDs of precision, repeatability, and stability tests were not more than 2% (n=6). The average recovery rates were 92.54%-105.55%, and the RSDs were 0.83%-1.93% (n=6). The average contents of 11 components were 0.744, 5.014, 0.646, 0.431, 0.069, 0.582, 0.979, 2.754, 0.157, 1.284 and 2.943 mg/g, respectively. CONCLUSIONS The constructed HPLC fingerprint and content determination methods are simple, accurate and stable, which can provide reference for quality control of G. delavayi. Xanthotoxin, chlorogenic acid, isochlorogenic acid A, luteolin-7-O- β -D-glucoside, isochlorogenic acid C and new chlorogenic acid can be used as markers for G. delavayi.
5.A multicentre retrospective study of house dust mite allergen preparation treating multi-sensitized allergic rhinitis patients
Zhouxian PAN ; Shengyang YAO ; Yongshi YANG ; Lisha LI ; Ruonan CHAI ; Wenchao GUAN ; Xiaoshang LOU ; Chuanhe LIU ; Li SHA ; Yanmin BAO ; Shijie ZHUANG ; Yin WANG ; Kai GUAN ; Rongfei ZHU
Chinese Journal of Preventive Medicine 2025;59(6):834-843
Objective:To investigate, for multi-sensitized allergic rhinitis (AR) patients allergic to dust mites combined with other allergens (pollen, mold, animal dander, etc.), whether the single dust mite subcutaneous immunotherapy (SCIT) can improve the specific symptoms caused by other allergens in the patients, and to analyze the relationship between the effectiveness of symptom improvement in these patients and the type, quantity and severity of the allergens.Methods:A multicenter retrospective study was conducted to collect mul-sensitized AR patients from allergy or respiratory departments of 5 hospitals who received house dust mite allergen preparation SCIT for 12 to 36 months and met other inclusion and exclusion criteria from February to July 2024. General clinical data were collected and the perennial or seasonal symptoms before and after treatment were evaluated with visual analogue scale (VAS) to assess whether there was an perennial or allergen-specific symptom improvement (VAS score decrease ≥30%), by which the patients were divided into effective group and ineffective. R software was used to analyze the differences between groups by using Fisher′s exact test and Mann-Whitney U test. Results:A total of 62 patients were enrolled, and the treatment were effective in 39 of them, with an effective rate of 62.9%. For allergen-specific symptoms, the median age of the effective group was higher than that of the ineffective group (12 years old vs. 8 years old, P=0.039), and the effective rate in dust mite specific immunoglobin E (sIgE) grade ≤5 group was higher than that in sIgE grade >5 group (81.6% vs. 45.5%, P=0.008), and the effective rate of mold sIgE grade ≤2 group was higher than that of sIgE grade >2 group (83.3% vs. 28.6%, P=0.045), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). For perennial symptoms, the effective rate in the mold grade ≤2 group was higher than that in the sIgE grade >2 group (91.3% vs. 28.6%, P=0.010), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). There was no significant correlation between the treatment effectiveness of perennial or allergen-specific symptoms and the number of combined allergens, the grade of skin test, and the difference between the grade of combined allergens and that of dust mites ( P>0.05). Conclusion:Among the patients with multi-sensitized AR allergic to dust mites included in this study, single dust mite SCIT is effective in some of them, and for allergen-specific symptoms, the effective group was elder, and dust mite sIgE grade 6 and mold sIgE grade ≥2 was related to the low effective rate of SCIT. The present results are insufficient for selecting single or multiple AIT in any type of multi-sensitized patients.
6.Development of a prediction model for ascending aortic dilatation in patients with normally functioning bicuspid aortic valves using LASSO-Logistic regression
Sijing HE ; Ning YAN ; Xue YANG ; Lili WANG ; Xingyue YANG ; Lisha NA
Chinese Journal of Ultrasonography 2025;34(11):967-975
Objective:To identify the risk factors for ascending aortic dilatation and develop a prediction model using LASSO-Logistic regression in patients with normally functioning bicuspid aortic valves(BAV).Methods:Eight-four adult patients with BAV diagnosed as having normal valve function by transthoracic echocardiography who attended to the General Hospital of Ningxia Medical University between June 2024 and April 2025 were prospectively selected,there were 42 patients with ascending aortic dilatation and 42 patients without dilatation.The patients were divided into a training set(60 cases)and a test set(24 cases)using stratified random sampling at a ratio of 7 to 3 via the R caret package. All subjects underwent transthoracic echocardiography,lipid and plasma matrix metalloproteinases(MMP)and tissue inhibitors(TIMP)levels detection. The inverse probability of treatment weighting(IPTW)method was employed to control for potential confounding factors. LASSO and multifactorial binary Logistic regression was applied to screen the independent risk factors for ascending aortic dilatation of BAV and development a nomogram prediction model. The accuracy,consistency and clinical applicability of the prediction model were evaluated by applying the ROC curve,calibration curve,and decision curve analysis(DCA),respectively.Results:①After adjustment for IPTW,LASSO-Logistic regression analysis identified left ventricular global longitudinal strain(LVGLS)and plasma MMP-2 levels as independent risk factors for ascending aortic dilatation in BAV patients with normal valve function.②The nomogram prediction model constructed based on the above screening features,and the area under the curve(AUC)of ROC for the training set and test set were 0.917 and 0.903,with specificities of 0.867 and 0.917,and sensitivities of 0.933 and 0.916,respectively. ③Calibration curves demonstrated satisfactory alignment,with C-indices of 0.908(95% CI=0.879~0.937)for the training set and 0.903(95% CI=0.874 - 0.932)for the test set. Hosmer-Lemeshow goodness-of-fit tests indicated strong consistency between predicted and observed outcomes,with P-values of 0.138 and 0.750 for the training and test sets,respectively.The DCA curve demonstrated that within a threshold probability range of 0.04 - 0.90 in the test set,the clinical decision-making model provided a higher net benefit rate for patients with BAV. Conclusions:LVGLS absolute value reduction and elevated plasma MMP-2 levels are independent risk factors for predicting ascending aortic dilatation in BAV patients with normal valve function. The prediction model based on LASSO-Logistic regression has good predictive value,providing a scientific basis for clinical decision-making in patients with BAV and aortic diseases.
7.Effect of culture time in vitro on maturity of induced pluripotent stem cell-derived cardiomyocytes
Tinglin XIONG ; Lisha ZHANG ; Dewei WANG ; Haiping CAO ; Yan YANG
Chinese Journal of Tissue Engineering Research 2025;29(25):5304-5310
BACKGROUND:It has been proved that induced pluripotent stem cells can differentiate into cardiomyocytes,but there are few reports on the maturity of differentiated cardiomyocytes.OBJECTIVE:To explore the effect of prolonging the induced differentiation time on the morphology,sarcomere length,binuclear cell content,cardiac gene expression,cardiac protein expression,and mitochondrial function of cardiomyocytes derived from induced pluripotent stem cells.METHODS:Bone morphogenetic protein 4,CH IR 99021,and IWR1 were used to induce pluripotent stem cells to differentiate into cardiomyocytes,and differentiated cardiomyocytes were collected on days 20 and 40 respectively.The expression levels of cardiac genes and proteins in differentiated cardiomyocytes were detected by RT-PCR and immunofluorescence,respectively.LAS X image analysis software was used to analyze the morphology and sarcomere length of differentiated cardiomyocytes.MitoTracker Green FM mitochondrial staining was used to detect total mitochondria.JC-1 mitochondrial staining was used to detect mitochondrial membrane potential.RESULTS AND CONCLUSION:Differentiated card io myocytes on day 40 had longer cell circumference and sarcomere length,and larger cell area than those on day 20(P<0.05).The proportion of multinucleated cells rose sharply from about 16%on day 20 to about 29%on day 40(P<0.05).Differentiated cardiomyocytes on day 40 had gene expression levels that were more similar to those of the primary cardiomyocytes,and the expression levels of SERCA2A,Cx-43,and α-MHC genes were significantly higher than on day 20(P<0.05).Compared with the differentiated cardiomyocytes on day 20,the expression density of TNNT2 and α-MHC protein was relatively higher,the distribution density of mitochondria was larger,and the number of functional mitochondria was greater on day 40(P<0.05).The results show that prolonging the induced differentiation time can increase the maturity of differentiated cardiomyocytes by increasing the length of sarcomere and the number of functional mitochondria,as well as improving the expression levels of cardiac genes and proteins.
8.Study of dynamic transcriptome during mitosis of HAP1 cells
Xueli WU ; Yurong YANG ; Yongli BAO ; Rucheng WU ; Lisha WANG ; Yang CHEN
Basic & Clinical Medicine 2025;45(6):786-792
Objective To comprehensively understand the map of transcripts during mitosis and their regulatory mechanisms of HAP 1 cells by conducting transcriptome sequencing analysis after being released by mitotic synchro-nization arrest.Methods HAP1 cells were subjected to mitotic synchronous arrest with nocodazole and samples were collected after 0,20,80 min release,and RNA sequencing(RNA-seq)were performed.The transcriptome data was cleaned and the differentially expressed genes,expression trend clustering and functional enrichment com-bined with the protein interaction network were analyzed to explore the changes of signaling pathways in HAP 1 cells during mitosis.Results The transcriptome of HAP1 cells after synchronous release from mitosis underwent significant changes in time series,and differential gene cluster analysis revealed four gene clusters were enriched in important biological processes such as p53 signaling and cytoplasmic translation.Conclusions The transcriptome time-dependent dynamic changes during mitosis in HAP1 cells are coordinated regulation of key signaling pathways including cellular stress response,translational control and chromatin remodeling,ensuring a balance between growth and stress response upon mitotic exit.
9.Clinical characteristics analysis of immune checkpoint inhibitor-related hepatotoxicity
Fan YANG ; Hongjian WANG ; Peng JIANG ; Anxiang HU ; Lisha CHU
Immunological Journal 2025;41(10):718-725
Objective To analyze the clinical characteristics of immune checkpoint inhibitor(ICI)-related hepatotoxicity(ICIH)in cancer patients.Methods A retrospective analysis was conducted on clinical data of cancer patients with ICIH from January 2019 to December 2024.Patients with Grade 1-2 liver injury were defined as the mild group,and those with Grade 3-4 liver injury were defined as the severe group.Results Among 13 patients with ICIH,10(76.92%)were males and 3(23.08%)were females,with a mean age of 67.8±5.2 years.Twelve patients(92.3%)were aged 60 years or above.ICIH first occurred between cycle 1 and cycle 14 after initial treatment,with the highest incidence observed within cycles 1-5.Combination therapy(combination chemotherapy or targeted agents)was used in 10 patients(76.92%).Among the 13 patients,the distribution of liver injury grades was as follows:1 case of Grade 1(7.69%),2 cases of Grade 2(15.38%),5 cases of Grade 3(38.46%),and 5 cases of Grade 4(38.46%).Liver injury types included hepatocellular(38.46%),cholestatic(38.46%),and mixed(23.08%).After drug discontinuation and supportive care,9 patients(69.23%)fully recovered,2(15.38%)improved,and 2(15.38%)showed no improvement.No significant differences were observed between the mild and severe groups in terms of age,body mass index,baseline lymphocyte count,platelet count,neutrophil count,monocyte count,alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,alkaline phosphatase,lymphocyte-to-monocyte ratio,neutrophil-to-lymphocyte ratio,and platelet-to-lymphocyte ratio(P>0.05).Conclusion ICIH typically occurs within 1 to 5 cycles after ICI administration,with non-specific clinical manifestations,which lead to a diagnosis of exclusion.Despite a generally favorable prognosis,severe ICIH can be fatal,particularly in patients with primary liver cancer.Prompt discontinuation of ICIs and initiation of Corticosteroid therapy can lead to timely improvement of patient's condition.
10.An Empirical Analysis on the Impact of China's Basic Medical Insurance System on the Equity of Health Based on BP Neural Network and ITSA
Cheng ZHANG ; Yanming LIN ; Yuehan YANG ; Lisha HOU ; Ju HUANG
Chinese Health Economics 2025;44(10):11-15
Objective:To analyze the impact of the universal coverage,integration and DRG/DIP payment method reform of Basic Medical Insurance(BMI)on the equity of the health service utilization and resource allocation.Methods:The 1998-2022 panel data on health service utilization and resources were collected for China.Health equity is measured using the Concentration Index(CI)and Theil index,and the impact of BMI reform on health equity is analyzed by BP neural network and ITSA.Results:Universal coverage,integration,and DRG/DIP payment reform of BMI had a positive effect on the number of health workers,beds,and admissions(P<0.001),and inhibited the growth of per capita hospitalization costs(P<0.05).The CI for the number of health workers and beds declined by 0.004 and 0.003 per year after universal coverage of BMI;and both still declined by 0.002 per year with a 5-year lag(P<0.05).The CI for the hospital admissions fell by 0.014 immediately after the DRG/DIP payment reform and by 0.012 per year thereafter(P<0.001).Conclusion:BMI reforms not only can contribute to improve the health service utilization and resources,but also it can also improve health equity.In addition,it has a lagged effect on improving health equity.

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