1.The application prospects of adeno-associated virus vectors in liver fibrosis
Suyu XIAO ; Sisi YAO ; Qing LI ; Tingzheng ZHAN
Journal of Clinical Hepatology 2026;42(4):972-979
Liver fibrosis is a critical pathological stage in the progression of various chronic liver diseases to liver cirrhosis and liver cancer, and it is characterized by the activation of hepatic stellate cells and excessive deposition of extracellular matrix. There are currently limited clinical treatment methods for liver fibrosis, and gene therapy has attracted increasing attention as a promising intervention strategy. Owing to its advantages of low immunogenicity, strong tissue tropism, and long-term gene expression, adeno-associated virus (AAV) has become an ideal vector for gene therapy. This article systematically reviews the structural and functional features of AAV, the tissue-targeting properties of different serotypes, and the methods for preparation and purification of recombinant AAV and focuses on the advances in the application of AAV-mediated gene overexpression, gene silencing, gene editing, and cellular reprogramming in mechanism research and intervention of liver fibrosis, as well as the challenges in clinical translation and corresponding strategies. AAV-mediated gene therapy is expected to provide novel tools and strategies for the precise treatment and mechanism study of liver fibrosis.
2.Analysis of Mechanism of Exosomes of BMSC Modified with Bushen Yisui Capsules on Promoting Differentiation and Maturation of OLN-93 Oligodendrocytes via Regulating miR-15b/Wnt Signaling Pathway
Sisi LIU ; Chunyu LI ; Chen LI ; Haixin LI ; Lei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):115-125
ObjectiveTo investigate the effect and molecular mechanism of exosomes derived from bone marrow mesenchymal stem cells(BMSC-exos) modified with Bushen Yisui capsule(BSYS)-containing serum on promoting the differentiation and maturation of OLN-93 oligodendrocytes by regulating miR-15b/Wnt signaling pathway. MethodsOLN-93 cells were divided into 5 groups, including the normal(NC) group, BMSC-exos group, BSYS-BMSC-exos group, BSYS-BMSC+LV-miR-15b-5p inhibitor-exos group, and BSYS-BMSC+LV-miR-15b-5p NC-exos group. DiR staining was used to observe the uptake of Exos by OLN-93 cells. The effective dosage of BSYS-BMSC-exos on OLN-93 cells was assessed by cell proliferation and activity assay(CCK-8). Stable BMSCs lentiviral transfection strains were established to inhibit miR-15b-5p expression in both BMSCs and their exos, and transfection efficiency was verified by real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) detection of miR-15b-5p. The expressions of 2′,3′-cyclic nucleotide 3′-phosphodiesterase(CNPase) and myelin proteolipid protein(PLP) in OLN-93 cells were detected by immunocytochemistry(ICC) and Western blot. The mRNA expressions of miR-15b-5p and Wnt3a in OLN-93 cells were detected by Real-time PCR, and the protein expression of Wnt3a was measured by Western blot. The expression levels of key molecules in the Wnt/β-catenin signaling pathway of OLN-93 cells, including glycogen synthase kinase(GSK)-3β, β-catenin, and T-cell specific transcription factor 4/transcription factor 7-like 2(TCF4/TCF7L2), were measured by Real-time PCR and Western blot. ResultsDiR-labeled Exos were efficiently taken up by OLN-93 cells. The CCK-8 assay results indicated that 20 mg·L-1 of BSYS-BMSC-exos exhibited the most significant effect in enhancing OLN-93 cell viability(P<0.01) and this dosage was selected for subsequent experiments. Following lentiviral transfection of BMSCs, Real-time PCR results revealed that miR-15b-5p was significantly suppressed in BMSCs(P<0.01), and miR-15b-5p was also notably inhibited in BSYS-BMSC-exos(P<0.01). ICC analysis further revealed an increase in the number of differentiated, mature CNPase and PLP-positive cells following BSYS-BMSC-exos treatment(P<0.01). Western blot results demonstrated that the protein expression of CNPase and PLP was significantly enhanced with BSYS-BMSC-exos treatment(P<0.01). Additionally, BSYS-BMSC-exos also increased the expression levels of miR-15b-5p and p-β-catenin proteins in OLN-93 cells, while decreased the mRNA and protein expressions of Wnt3a, as well as the mRNA expressions of β-catenin and TCF4/TCF7L2, and the protein expression level of p-GSK-3β(Ser9) was significantly reduced(P<0.05, P<0.01). After the transfection of miR-15b-5p inhibitor into BSYS-BMSC-exos, the above effects were significantly diminished(P<0.05, P<0.01). ConclusionBSYS-BMSC-exos facilitate the differentiation and maturation of OLN-93 cells, and its mechanism is related to the upregulation of miR-15b-5p in OLN-93 cells, which inhibits the expression of Wnt3a and thereby suppresses the Wnt signaling pathway.
3.Hyperoside Alleviates LPS-induced Inflammation in Zebrafish Model via TLR4/MyD88/NF-κB Pathway
Qing LAN ; Anna WANG ; Feifei ZHOU ; Keqian LIU ; Zhao LI ; Wenjing YU ; Shuyao TANG ; Ping LI ; Shaowu CHENG ; Sisi DENG ; Zhenyan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):63-72
ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside (Hyp) on lipopolysaccharide (LPS)-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L-1 LPS or immersed in 1 g·L-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25, 50, and 100 mg·L-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate, malformation rate, body length, and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses, and macrophage migration was observed by fluorescence microscopy. Additionally, the mRNA levels of inflammation-related genes, including interleukin-1β (IL-1β), interleukin-6 (IL-6), chemokine C-C motif ligand 2 (CCL2), chemokine C-X3-C motif receptor 1 (CX3CR1), chemokine C-C motif receptor 2 (CCR2), and genes associated with the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway, were measured by Real-time quantitative polymerase chain reaction(Real-time PCR). ResultsCompared with the pure water injection group, the model group exhibited increased mortality, malformation rates and yolk sac area ratio (P0.01), reduced body length (P0.01), increased total swimming distance and high-speed swimming duration (P0.01), and up-regulated mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.01). Hyp at low, medium and high doses, as well as aspirin, reduced the mortality and malformation rates (P0.05,P0.01), increased the body length (P0.05,P0.01), decreased the yolk sac area ratio (P0.01), reduced the high-speed swimming duration (P0.01), and down-regulated the mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.05,P0.01) compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish, thereby exerting the anti-inflammatory effect.
4.Differentiation and treatment of urticarial vasculitis based on the theory of Xuanfu-collateral theory
Keyi LIU ; Ye TIAN ; Yue DU ; Ziye XI ; Haomin ZHANG ; Sisi LU ; Xin LI ; Lingling LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):542-546
Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.
5.Value of combined detection of serum mitogen-activated protein kinase 1 and lysyl oxidase-like protein 2 in early diagnosis of cervical cancer
Xiaodan JIANG ; Huifang WANG ; Sisi CHEN ; Yiman TANG ; Zhuang ZHANG ; Meng LI
Journal of Clinical Medicine in Practice 2025;29(15):58-62,78
Objective To explore the value of combined detection of serum mitogen-activated protein kinase 1(MAPK1)and lysyl oxidase-like protein 2(LOXL2)in early diagnosis of cervical cancer.Methods A total of 218 patients with cervical lesions were selected as study group(103 ca-ses in cervical cancer group,115 cases in benign tumor group).Additionally,100 patients with cer-vical intraepithelial neoplasia grade Ⅱ were selected as precancerous lesion group,and 79 healthy in-dividuals undergoing physical examinations during the same period were selected as control group.Se-rum levels of MAPK1 and LOXL2 were measured in each group.Pearson correlation analysis was used to evaluate the correlations of serum MAPK1 and LOXL2 levels in patients with cervical cancer.Logistic regression analysis was performed to screen influencing factors for the occurrence of cervical cancer.Receiver operating characteristic(ROC)curves were plotted to assess the diagnostic efficacy of serum MAPK1 and LOXL2 for cervical cancer.Results Serum MAPK1 and LOXL2 levels in the study group were higher than those in the precancerous lesion group and the control group,and those in the precancerous lesion group were higher than those in the control group,with statistically signif-icant differences(P<0.05).The proportion of patients with high-risk human papillomavirus(HPV)infection and serum MAPK1 and LOXL2 levels in the cervical cancer group were higher than those in the benign tumor group,with statistically significant differences(P<0.05).Serum MAPK1 and LOXL2 levels in patients with stage Ⅲ to Ⅳ cervical cancer were higher than those in patients with stage Ⅰ to Ⅱ cervical cancer,with statistically significant differences(P<0.05).Pearson correlation analysis showed a positive correlation between serum MAPK1 and LOXL2 levels in patients with cervical cancer(r=0.468,P<0.001).Logistic regression analysis showed that high-risk HPV infection,MAPK1 and LOXL2 were all influencing factors for the occurrence of cervi-cal cancer(P<0.05).ROC curve analysis showed that the area under the curve(AUC)for com-bined diagnosis of serum MAPK1 and LOXL2 was 0.911,which was significantly greater than the AUCs for individual diagnoses(0.848 and 0.843,respectively).Conclusion Serum MAPK1 and LOXL2 levels in patients with cervical cancer are significantly upregulated,and the two indicators were positively correlated.High-risk HPV infection,serum MAPK1 and LOXL2 levels were influen-cing factors for the occurrence of cervical cancer.Combined detection of MAPK1 and LOXL2 levels is expected to assist in the diagnosis of cervical cancer.
6.Chinesization of Maternal Childbirth Fatigue Perception Questionnaire and its reliability and validity test
Huhua LIU ; Jinli GU ; Wenxiu ZHANG ; Rongrong WU ; Sisi WANG ; Lin LI
Journal of Clinical Medicine in Practice 2025;29(15):87-91
Objective To translate the Maternal Childbirth Fatigue Perception Questionnaire(MCFQ)into Chinese and examine its reliability and validity among women undergoing vaginal deliv-ery.Methods Following the Brislin translation model,the MCFQ was translated,back-translated,culturally adapted and pre-tested to develop a Chinese version.By using the convenience sampling method,574 parturients were selected for a questionnaire survey from January to April 2024,and the reliability and validity of the Chinese questionnaire were evaluated.Results The Chinese version of MCFQ consisted of 3 dimensions and 13 items,namely physical fatigue(7 items),perceived fatigue(3 items)and emotional fatigue(3 items).The item-level content validity index ranged from0.813 to 1.000,and the scale-level content validity index was 0.938.The overall Cronbach's α coefficient of the scale was 0.870,and the split-half reliability coefficient was 0.848.Confirmatory factor analysis demonstrated that the question naire had a good fit.Conclusion The Chinese version of MCFQ has good reliability and validity and can be used as an effective tool to assess the fatigue level of parturients during the delivery process.It is helpful for clinical medical staff to optimize the management of the la-bor process,improve the quality of delivery,and ensure the safety of mothers and infants.
7.Effect of Qinggan Bupi Jiangtang Decoction combined with acupuncture on glucose and lipid metabolism and cytokines in patients with overweight/obese type 2 diabetes mellitus
Wenlan GAO ; Wenyan WANG ; Sisi LI ; Xuefei WANG ; Yi CHEN ; Feng TAO ; Gan CAI
International Journal of Traditional Chinese Medicine 2025;47(1):29-35
Objective:To investigate the effect of Qinggan Bupi Jiangtang Decoction combined with acupuncture on glucose and lipid metabolism and cytokines in patients with overweight/obese T2DM.Methods:Randomized controlled trial. A total of 104 patient with overweight/obese T2DM who were admitted to the Shanghai Municipal Hospital of Traditional Chinese Medicine of Shanghai University of Traditional Chinese Medicine from September 2022 to March 2023 were selected as the research subjects. They were randomly divided into the control group (52 cases) and the combination group (52 cases). The control group was given conventional symptomatic treatment and treated with acupuncture. On this basis, the combination group was treated with Qinggan Bupi Jiangtang Decoction. The two groups were compared in terms of efficacy, TCM syndrome scores, glucose metabolism indicators, islet function indicators, lipid metabolism indicators, cytokines, and blood glucose control. Results:The total effective rate was 90.38% (47/52) in the combined group and 73.08% (38/52) in the control group, and the difference between the two groups was statistically significant ( χ2=5.22, P=0.022). After treatment, the TCM syndrome score (13.21±1.48 vs. 18.54±2.01, t=15.40) of the combination group was lower than that of the control group ( P<0.001). After treatment, the combination group FPG [(6.05 ± 1.01) mmol/L vs. (7.26 ± 1.13) mmol/L, t=5.73], 2 hPG [(8.23 ± 1.12) mmol/L vs. (10.41 ± 1.26) mmol/L, t=9.54], HbAlc [(5.84 ± 0.84) % vs. (6.31 ± 0.93) %, t=2.84] and HOMA-IR (2.57 ± 0.26 vs. 2.86 ± 0.30, t=3.75) were lower than those in the control group ( P<0.05), and HOMA-β (61.34 ± 6.75 vs. 56.69 ± 5.72, t=5.87) was higher than that of the control group ( P<0.05). After treatment, the combination group TC, TG and LDL-C were lower than those in the control group ( t values were 10.25, 5.35, 3.51, respectively, P<0.01), HDL-C was higher than that of the control group ( t=11.59, P<0.01). After treatment, the combination group CTRP12 [(296.05 ± 30.11) ng/L vs. (280.23 ± 28.44) ng/L, t=2.76], FGF-21 [(184.12 ± 19.05) μg/L vs. (170.04 ± 17.03) μg/L, t=2.77], Nesfatin1 [(0.92 ± 0.10) μg/L vs. (0.77±0.08) μg/L, t=5.99] and lipidin levels [(4.89±0.51) mg/L vs. (4.12±0.48) mg/L, t=8.58] were higher than those in the control group ( P<0.01). The combined group composite endpoint achievement rate was 53.85% (28/52), the 12-week HbA1c achievement rate was 80.77% (42/52), and the rate of no weight increase was 84.62% (44/52). The control group's composite endpoint achievement rate was 34.62% (18/52), the 12-week HbA1c achievement rate was 61.54% (32/52), and the rate of no weight increase was 67.31% (35/52). The differences between the two groups were statistically significant ( χ2 values were 3.90, 4.69, 4.27, respectively, and the P values were 0.048, 0.030, 0.039, respectively). The adverse reactions of the two groups were mainly mild nausea, skin rash and pruritus, the incidence of which was 15.38% (8/52) in the combination group and 9.62% (5/52) in the control group, and there was no significant difference between the two groups ( χ2=0.79, P=0.374). Conclusion:The therapeutic effect of Qinggan Bupi Jiangtang Decoction combined with acupuncture on overweight/obese T2DM patients is relatively clear, and it can regulate the glucose and lipid metabolism and cytokines of patients.
8.Application and progress of artificial intelligence in the analysis of retinal vascular parameters
Zhaoyang ZHAO ; Huilin LI ; Yanfeng SHANG ; Sisi MENG ; Shaofeng HAO
International Eye Science 2025;25(5):787-791
This review summarizes the applications and advancements of artificial intelligence(AI)in the analysis of retinal vascular parameters. Retinal vascular parameters, including vessel diameter, fractal dimension, vascular tortuosity, branching angles, and vessel density, are important indicators for assessing changes in the retinal vascular network structure. These parameters are not only related to various ophthalmic diseases but also reflect the conditions of systemic diseases such as diabetes and Alzheimer's disease. This article provides a detailed discussion on the advantages of AI technology in the automated identification and quantification of retinal vascular parameters, particularly in improving measurement efficiency and accuracy, and enabling the early detection and monitoring of various diseases. Additionally, the challenges faced by AI in the analysis of retinal vascular parameters were discussed, such as data standardization and insufficient sample diversity, and proposes directions for future research. By thoroughly analyzing the application of AI in retinal vascular parameter analysis, this article aims to offer new perspectives and methods for clinical diagnosis and early intervention of diseases, holding significant clinical significance and application prospects.
9.Huangqin decoction inhibits colorectal inflammatory cancer transformation by improving gut microbiome-mediated metabolic dysfunction
Lu LU ; Yuan LI ; Hang SU ; Sisi REN ; Yujing LIU ; Gaoxuan SHAO ; Weiwei LIU ; Guang JI ; Hanchen XU
Journal of Pharmaceutical Analysis 2025;15(5):1058-1071
Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2-3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced in-testinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12-/-mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.
10.Free inferior gluteal perforator flap for immediate breast reconstruction: a case report and literature review
Lan MU ; Junbo PAN ; Guisheng HE ; Xiuxiu CHEN ; Tao SONG ; Haohao JIAN ; Zuolei YANG ; Sisi WANG ; Huangfu WU ; Yazhen ZHANG ; Kun XIE ; Chuanwei SUN ; Wentian XU ; Guanghua FU ; Junzhang CHEN ; Bo LI ; Hengyu CHEN ; Yilian XU ; Mingmei HE ; Jinhui HUANG ; Peng LI
Chinese Journal of Microsurgery 2025;48(2):161-166
Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.


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