1.Analysis of depressive symptoms and predictive factors in children and adolescents in Inner Mongolia Autonomous Region
Guiwei CHEN ; Lu TONG ; Ziyu LI ; Xiaojuan GAO ; Ruiqi WANG ; Xiaolu ZHANG ; Le LIU ; Yinxia BAI
Sichuan Mental Health 2026;39(1):83-88
BackgroundIn recent years, the incidence of depression among adolescents has been increasing steadily, posing a serious threat to their physical and mental health and even leading to severe consequences such as self-harm and suicide. At the same time, the detection rate of subclinical depression symptoms among adolescents is even higher. Although these symptoms do not meet the clinical diagnostic criteria, they have significantly affected their quality of life, and their persistence over time may further develop into depression. Therefore, in-depth exploration of adolescent depression symptoms and the predictive factors holds significant practical significance and research value. However, up to now, no large-scale investigation and research on depression symptoms among children and adolescents has been conducted in Inner Mongolia Autonomous Region. ObjectiveTo understand the prevalence of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region, in order to provide references for formulating scientific and effective prevention strategies and intervention measures. MethodsBy using the cluster stratified random sampling method, 6 281 students from the third grade of primary school to the second grade of high school in 12 leagues and cities of Inner Mongolia Autonomous Region were selected in March 2024. A self-designed questionnaire and the Self-rating Depression Scale (SDS) were used for on-site investigation. ResultsA total of 6 058 (96.45%) children and adolescents completed the valid questionnaire survey, and 2 728 cases (45.03%) were found to have depressive symptoms. There were statistically significant differences in the detection rates of depressive symptoms among children and adolescents of different genders, ages, whether they were only children, different family types, family monthly income, parents' educational levels, and whether the mother was employed (χ2=33.769, 40.618, 48.593, 29.972, 142.648, 195.999, 168.190, 5.445, P<0.05 or 0.01).The results of the Logistic regression analysis showed that for children and adolescents, being female, aged between 12 and 16, over 16 years old, not being an only child, living in a reconstituted family, having a monthly family income of less than 5 000 yuan, and having parents with an education level of primary school or below were predictors of depressive symptoms (OR=1.241, 1.427, 1.273, 1.177, 1.549, 1.278, 1.462, 1.417, 1.514, 1.929, 1.660, 1.528, P<0.05 or 0.01). ConclusionThe detection rate of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region is relatively high. Factors that may predict depressive symptoms in children and adolescents include female gender, ages between 12 and 16, ages over 16 years old, non-only children, families with a restructured structure, monthly family income of less than 5 000 yuan, and parents with an education level of primary school or below. [Funded by Science and Technology Planning Project of the Inner Mongolia Autonomous Region (number, 2022YFSH0119)]
2.A Single-cell Transcriptomic Study of Wenyang Jiedu Granules in Alleviating Influenza Virus Pneumonia by Suppressing Interferon Responses and Apoptotic Pathways in AT1 Cells
Jingyan XIN ; Shengle QIN ; Taoyu CHEN ; Yuntao LIU ; Xiaolu WANG ; Chaofeng LIANG ; Zhongde ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):76-85
ObjectiveTo investigate the molecular mechanisms by which Wenyang Jiedu granules (WYJD) alleviate influenza A virus (IAV)-induced pneumonia based on single-cell transcriptome sequencing. MethodsThirty female BALB/c mice were randomly divided into a blank control group (Control), IAV group, and WYJD low-, medium-, and high-dose groups (WYJD-L, WYJD-M, WYJD-H; 2.925, 5.85, 11.7 g·kg-1, n=6). Except for the Control group, all other groups were intranasally inoculated with IAV subtype H1N1 (A/PR/8/34) to establish an infection model. Two hours after modeling, drug administration was initiated and continued for 5 consecutive days, with daily monitoring of body weight and general condition. On day 6, mice were sacrificed and samples were collected. Lung index was calculated, and histopathological examination of lung tissue was performed. Lung tissues from the Control, IAV, and WYJD-H groups were subjected to single-cell transcriptome sequencing (n=3), focusing on type I alveolar epithelial cells (AT1) to analyze changes in gene expression and signaling pathways. Western blot was used to detect the expression changes of relevant proteins to validate the single-cell sequencing results. ResultsCompared with the Control group, the IAV group exhibited significantly decreased body weight (P<0.05) and significantly increased lung index (P<0.05). Compared with the IAV group, all WYJD-treated groups exhibited significantly increased body weight (P<0.01) and significantly decreased lung index (P<0.01). Single-cell sequencing analysis revealed that WYJD inhibited overactivation of interferon and inflammatory signaling pathways in AT1 cells after IAV infection, including interferon-γ response, interferon-α response, tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), and interleukin-6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) pathways. Compared with the Control group, the number of AT1 cells in the IAV group showed a decreasing trend. Compared with the IAV group, the WYJD-H group showed an increasing trend, although neither difference was statistically significant. Further analysis of AT1 cell subpopulation gene expression showed that, compared with the Control group, the IAV group exhibited increased expression of pro-apoptotic genes FAS cell surface death receptor (FAS) and cyclin-dependent kinase inhibitor 1A (CDKN1A), a significant increase in tumor protein p53 (Tp53) expression (P<0.05), and significant decreases in expression of the AT1 marker gene advanced glycosylation end-product-specific receptor (AGER) and membrane structural gene caveolin1 (CAV1) (P<0.05, P<0.01). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of FAS, CDKN1A, and Tp53 (P<0.05, P<0.01), and significantly increased expression of AGER and CAV1 (P<0.05, P<0.01). Regarding interferon response-related genes, compared with the Control group, the IAV group showed increased expression of interferon-stimulated gene 15 (ISG15), interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), signal transducer and activator of transcription 2 (STAT2), bone marrow stromal cell antigen 2 (BST2), and C-X-C motif chemokine ligand 10 (CXCL10), with a significant increase in 2′,5′-oligoadenylate synthetase-like protein 1 (OASL1) (P<0.05). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of all the above genes, with highly significant differences for ISG15, IFIT3, STAT2, BST2, and OASL1 (P<0.01), and a significant difference for CXCL10 (P<0.05). Among inflammation-related genes, compared with the Control group, the IAV group showed significantly increased expression of intercellular adhesion molecule 1 (ICAM1), tumor necrosis factor alpha-induced protein 3 (TNFAIP3), keratin 8 (KRT8), tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), and TNFRSF1B (P<0.01), and increased expression of NFKBIA, a negative regulator of NF-κB (P<0.05). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of KRT8 and TNFRSF1B (P<0.05), while ICAM1, NFKBIA, TNFAIP3, and TNFRSF1A showed decreasing trends without statistical significance. Western blot validation showed that, compared with the Control group, protein expression levels of ISG15, FAS, p53, and phosphorylated p65 (p-p65) in lung tissue of the IAV group were significantly increased (P<0.05, P<0.01). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of these proteins (P<0.05, P<0.01). ConclusionWYJD may alleviate viral pneumonia by targeting gene expression in AT1 cells, inhibiting overactivated interferon and inflammatory signaling pathways after IAV infection, and downregulating pro-apoptotic signaling, thereby reducing alveolar epithelial injury.
3.Efficacy and Safety of Radiotherapy Combined with Liposomal Irinotecan, Camrelizumab, and Anti-angiogenic Therapy in Advanced Bone and Soft Tissue Sarcoma: A Retrospective Subgroup Analysis of CAP Study
Wanru WANG ; Yuchen GE ; Xiaolu WANG ; Juan LIU ; Yue CAO ; Baorui LIU ; Jie SHEN ; Rutian LI
Cancer Research on Prevention and Treatment 2026;53(7):542-548
Objective To evaluate the efficacy and safety of a combination therapy regimen comprising stereotactic body radiation therapy (SBRT) combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy (CAP) in patients with advanced bone and soft tissue sarcomas. Methods This study is a prospective subgroup analysis of the multicenter, open-label, single-arm phase Ⅱ CAP trial (NCT04569916), which enrolled 60 patients with advanced solid tumors who had progressed after standard therapy between November 2020 and February 2023, including 11 patients with advanced bone and soft tissue sarcomas. All patients received sequential liposomal irinotecan within 48 hours after stereotactic body radiotherapy (SBRT), followed by maintenance therapy with camrelizumab and an anti-angiogenic agent until disease progression or intolerable toxicity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results In the bone and soft tissue sarcoma subgroup (n=11), three patients achieved partial response (PR), five had stable disease (SD), and three experienced disease progression (PD). ORR was 27.3%, and DCR was 72.7%. mPFS was 5.8 months (95%CI: 2.2-10.3), and mOS not reached. Regarding safety, adverse reactions primarily included bone marrow suppression, fatigue, and gastrointestinal reactions, indicating overall manageable toxicity. Conclusion As a subgroup analysis of the CAP study, this research suggests that radiotherapy combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy demonstrates certain efficacy in advanced bone and soft tissue sarcomas that have failed multiple lines of treatment, with overall manageable adverse reactions. Future studies should expand the sample size.
4.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
5.The impact of different chest compression frequencies on cardiopulmonary resuscitation outcomes in domestic pigs.
Nana XU ; Jiabi ZHANG ; Jialin LUO ; Li WANG ; Yong CHEN ; Lijun ZHOU ; Bihua CHEN ; Lan LUO ; Xiaolu LIU ; Shuju LUO ; Yong WANG ; Zunwei LUO ; Li DING ; Mei LI ; Manhong ZHOU
Chinese Critical Care Medicine 2025;37(5):472-476
OBJECTIVE:
To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR).
METHODS:
Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (PETCO2). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy.
RESULTS:
With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, PETCO2, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, PETCO2 (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [PETCO2, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage.
CONCLUSIONS
Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals
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Cardiopulmonary Resuscitation/methods*
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Swine
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Male
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Heart Arrest/therapy*
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Heart Massage/methods*
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Hemodynamics
6.Fabrication and evaluation of dexmedetomidine hydrochloride microneedles based on 3D printing.
Yuanke YANG ; Xiaolu HAN ; Xianfu LI ; Xiaoxuan HONG ; Shanshan YANG ; Chunyan LIU ; Zengming WANG ; Aiping ZHENG
Chinese Journal of Biotechnology 2025;41(8):3214-3227
Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics*
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Printing, Three-Dimensional
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Needles
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Drug Delivery Systems/methods*
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Administration, Cutaneous
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Animals
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Microinjections/instrumentation*
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Skin Absorption
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Skin/metabolism*
7.Analysis of the clinical features of postnatal cytomegalovirus infection in very preterm infants or very low birth weight infants
Mengting JIANG ; Taixiang LIU ; Shanshan XU ; Hongfang MEI ; Tian XIE ; Xiaolu MA ; Zheng CHEN ; Yanping XU
Chinese Journal of Pediatrics 2025;63(3):259-265
Objective:To analyze the clinical features of postnatal cytomegalovirus (pCMV) infection in very preterm infants or very low birth weight infants.Methods:This was a case-control study. A total of 50 very preterm or very low birth weight infants who were hospitalized and diagnosed with pCMV infection in the Neonatal Intensive Care Unit of Children′s Hospital, Zhejiang University School of Medicine from January 2019 to June 2024, were enrolled as the pCMV group. Meanwhile, through propensity score matching, each infant in the pCMV group was paired with a very preterm or very low birth weight infant without cytomegalovirus infection during the same period, constituting the control group, also consisting of 50 cases. Subsequently, the pCMV group was divided into a treated subgroup and an untreated subgroup according to antiviral treatment. Clinical data of all enrolled infants, including clinical features, laboratory test results, and clinical outcomes were collected. Differences in relevant parameters were analyzed using with χ2 test or continuity-corrected χ2 test or Fisher′s exact test, independent-samples t test, Mann-Whitney U test as appropriate. Logistic regression was employed to analyze the risk factors, and Spearman correlation analysis was applied for non-normal distribution data or ordinal data. Results:There were no significant differences between the pCMV group and the control group in terms of gestational age, birth weight, proportion of male infants, Apgar score at the 1 st minute and 5 th minute and days of breastfeeding during the first 3 weeks of life (all P>0.05). Compared with the control group, the duration of hospital stay and invasive mechanical ventilation were both longer in the pCMV group (both P<0.05). The risks of bronchopulmonary dysplasia, retinopathy of prematurity, and hearing impairment were all higher in the pCMV group when compared with the control group(all P<0.05). The body weight and body length of the infants in the pCMV group were both lower than those of in the control group at the corrected gestational age of 36 weeks (both P<0.05). pCMV infections were associated with the increased incidence of both necrotizing enterocolitis ( OR=11.50, 95% CI 1.94-68.30, P=0.007) and severe intraventricular hemorrhage ( OR=6.82, 95% CI 1.19-38.97, P=0.031) in very preterm infants or very low birth weight infants. In the treated group, the platelet count was significantly improved after 6-8 weeks of antiviral treatment compared with that before treatment ((245±19)×10 9/L vs. (119±14)×10 9/L, t=5.37, P<0.001). Conclusions:Very preterm infants or very low birth weight infants with postnatal cytomegalovirus infection have longer hospital stay and duration of invasive mechanical ventilation, and are highly susceptible to bronchopulmonary dysplasia, retinopathy of prematurity, hearing impairment, and growth restriction. Antiviral treatment can effectively ameliorate thrombocytopenia in these infants.
8.Strategies for Optimizing Tumor Physical Microenvironment to Enhance in Situ Vaccine Efficacy
Han LI ; Xiaolu WANG ; Changhua YU ; Baorui LIU ; Rutian LI
Cancer Research on Prevention and Treatment 2025;52(10):840-847
In situ tumor vaccine has become an important strategy in cancer immunotherapy owing to its ability to induce immune responses locally and overcome tumor heterogeneity. However, the abnormal structure and mechanical properties of the tumor’s physical microenvironment significantly limit the efficiency of vaccine delivery and immune efficacy. In this review, the key factors in the tumor’s physical microenvironment, including solid pressure, interstitial fluid pressure, matrix stiffness, and tissue microstructure, are systematically discussed. Their obstructive roles in immune cell infiltration, antigen presentation, and immune activation are analyzed. The potential of approaches, such as radiotherapy, anti-angiogenic therapy, extracellular matrix degradation agents, nanomaterials, and hydrogel delivery platforms, in reshaping the tumor’s physical microenvironment is explored. This review aims to offer theoretical and practical guidance for optimizing in situ vaccine strategies through the regulation of the tumor’s physical microenvironment, ultimately advancing the precision and effectiveness of cancer immunotherapy.
9.Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway
Yinlian WEN ; Jinfeng SHANG ; Bohong WANG ; Wanting WEI ; Xiaolu ZHANG ; Guijinfeng HUANG ; Xin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):159-167
ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion (I/R) injury in rats based on the changes of pericytes mediated by Ras homolog family member A (RHOA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) pathway. MethodsNinety rats (15 rats for each group) were randomly divided into a sham operation group, a model group, a positive control group receiving Ginkgo biloba extract (21.6 mg·kg-1), and groups receiving Naoxintong capsules at low, medium, and high doses of 55, 110, and 220 mg·kg-1 (NXT-L, NXT-M, and NXT-H groups), respectively. Except for those in the sham operation group, all rats were subjected to transient middle cerebral artery occlusion (tMCAO) to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager, and the cerebral infarction rate was calculated using 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. Pathological changes were observed by hematoxylin-eosin (HE) staining and Nissl staining, while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of RHOA, ROCK1, platelet-derived growth factor receptor β (PDGFRB), α-smooth muscle actin (α-SMA), tight junction protein (ZO-1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). ResultsCompared with the sham operation group, the model group exhibited decreased neurological function scores, higher percentage reduction in blood flow, and increased cerebral infarction rates (P<0.01). Additionally, cortical neuronal nucleus shrinkage, edema, a decreased number of Nissl bodies, reduced pericyte area, elevated albumin content in the cortex (P<0.05), and increased ischemic modified albumin levels (P<0.01) were observed. The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were increased (P<0.01), while those of ZO-1 were decreased. Compared with the model group, all treatment groups showed improved neurological function scores, lower percentage reduction in blood flow, reduced cerebral infarction rates (P<0.01), alleviated cortical histological changes, increased number of Nissl bodies, expanded pericyte area, decreased albumin content in the cortex, and reduced ischemia-modified albumin levels (P<0.01). The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were decreased (P<0.01), while those of ZO-1 were increased. Among the treatment groups, the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply, reduce microcirculation disturbance, and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.
10.Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway
Yinlian WEN ; Jinfeng SHANG ; Bohong WANG ; Wanting WEI ; Xiaolu ZHANG ; Guijinfeng HUANG ; Xin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):159-167
ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion (I/R) injury in rats based on the changes of pericytes mediated by Ras homolog family member A (RHOA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) pathway. MethodsNinety rats (15 rats for each group) were randomly divided into a sham operation group, a model group, a positive control group receiving Ginkgo biloba extract (21.6 mg·kg-1), and groups receiving Naoxintong capsules at low, medium, and high doses of 55, 110, and 220 mg·kg-1 (NXT-L, NXT-M, and NXT-H groups), respectively. Except for those in the sham operation group, all rats were subjected to transient middle cerebral artery occlusion (tMCAO) to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager, and the cerebral infarction rate was calculated using 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. Pathological changes were observed by hematoxylin-eosin (HE) staining and Nissl staining, while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of RHOA, ROCK1, platelet-derived growth factor receptor β (PDGFRB), α-smooth muscle actin (α-SMA), tight junction protein (ZO-1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). ResultsCompared with the sham operation group, the model group exhibited decreased neurological function scores, higher percentage reduction in blood flow, and increased cerebral infarction rates (P<0.01). Additionally, cortical neuronal nucleus shrinkage, edema, a decreased number of Nissl bodies, reduced pericyte area, elevated albumin content in the cortex (P<0.05), and increased ischemic modified albumin levels (P<0.01) were observed. The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were increased (P<0.01), while those of ZO-1 were decreased. Compared with the model group, all treatment groups showed improved neurological function scores, lower percentage reduction in blood flow, reduced cerebral infarction rates (P<0.01), alleviated cortical histological changes, increased number of Nissl bodies, expanded pericyte area, decreased albumin content in the cortex, and reduced ischemia-modified albumin levels (P<0.01). The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were decreased (P<0.01), while those of ZO-1 were increased. Among the treatment groups, the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply, reduce microcirculation disturbance, and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.

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