1.Gandou Bushen decoction ameliorates ovarian injury in murine hepatolenticular degeneration via the AGE/RAGE/NF-κB pathway.
Pengyu JIANG ; Limin WU ; Hui HAN
Journal of Zhejiang University. Medical sciences 2025;():1-15
OBJECTIVES:
To investigate the protective effect and underlying mechanism of Chinese herb medicine Gandou Bushen decoction (GBD) on ovarian injury in murine hepatolenticular degeneration (HLD) model.
METHODS:
The chemical constituents of GBD were analyzed using liquid chromatography-mass spectrometry (LC-MS). Forty female C3He-Atp7btx-J mice (6-week-old) were randomly divided into model, penicillamine (positive control), low-dose GBD, and high-dose GBD groups. Ten DL syngeneic female mice served as the normal control group. Body and ovarian weights were measured to calculate the ovarian coefficient. Ovarian copper content was detected by complexometric colorimetry. Histopathological and ultrastructural changes were observed by hematoxylin-eosin staining and transmission electron microscopy, respectively. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing was performed to identify differentially expressed genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A copper overload cell model was established in ovarian granulosa cells(iCell-0114a)by inducing them with copper sulfate. Cells were divided into normal control, model control, and low-, medium-, and high-dose GBD groups. The mRNA expression of FSH receptor (FSHR), steroidogenic acute regulatory protein (StAR), insulin-like growth factor-1 (IGF-1), receptor for advanced glycation end products (RAGE), and nuclear factor κB (NF-κB) was detected by quantitative reverse transcription polymerase chain reaction. The levels of TNF-α, IL-1β, and IL-6 were measured by ELISA. Superoxide dismutase (SOD) activity was measured using a WST-1 assay. Reactive oxygen species (ROS) levels were measured using DCFH-DA fluorescence, and mitochondrial membrane potential was assessed using JC-1 staining coupled with flow cytometry. Protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, advanced glycation end products (AGE), RAGE, and NF-κB was determined by Western blotting.
RESULTS:
A total of 1465 chemical components were identified in GBD. Compared with the normal control group, the model group showed decreased body weight, ovarian weight, and ovarian coefficient (all P<0.01). GBD treatment alleviated tissue copper deposition (P<0.01), improved ovarian histomorphology and ultrastructure, and increased serum levels of FSH, LH, estradiol, and progesterone (all P<0.01). RNA sequencing identified 507 differentially expressed genes. KEGG enrichment analysis indicated that the mechanism underlying GBD's protective effects primarily involved the AGE/RAGE/NF-κB signaling pathway. In copper-overloaded granulosa cells, GBD dose-dependently increased the mRNA expression of FSHR, StAR, and IGF-1, reduced the levels of TNF-α, IL-1β, and IL-6, increased SOD activity, and decreased ROS levels (all P<0.01). The medium- and high-dose GBD groups showed a lower percentage of cells with mitochondrial depolarization (both P<0.01). All GBD dose groups showed decreased expression of Bax and caspase-3 (all P<0.05), while the medium- and high-dose groups showed increased Bcl-2 expression. Furthermore, medium and high doses of GBD reduced the protein expression of AGE, RAGE, and NF-κB, and all doses downregulated the mRNA expression of RAGE and NF-κB (P<0.05 or P<0.01).
CONCLUSIONS
GBD ameliorates ovarian injury in HLD, and its mechanism of action is associated with the suppression of the AGE/RAGE/NF-κB signaling pathway.
2.Exploration of clear surgical margin in human papillomavirus positive oropharyngeal cancer treated with transoral robotic surgery.
Hongli GONG ; Chengzhi XU ; Chunping WU ; Pengyu CAO ; Yongzheng CHEN ; Jianfang WU ; Meiqin SHI ; Ming ZHANG ; Liang ZHOU ; Lei TAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(11):1016-1027
Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery(TORS) in treating human papillomavirus(HPV) -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage(≤T3 stage) oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival(OS) and progression-free survival(PFS). Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients(60 males, 66.7%) were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years(range: 39-84 years) old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender(P>0.05). Cox analysis identified surgical margins>2 mm as a significant factor improving PFS(HR=0.14, 95%CI 0.02-0.90, P=0.038). Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.
Adult
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Aged
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Aged, 80 and over
;
Female
;
Humans
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Male
;
Middle Aged
;
Carcinoma, Squamous Cell/virology*
;
Human Papillomavirus Viruses/isolation & purification*
;
Margins of Excision
;
Oropharyngeal Neoplasms/virology*
;
Papillomavirus Infections/virology*
;
Prognosis
;
Prospective Studies
;
Robotic Surgical Procedures/methods*
3.Standardized procedures and quality control in laparoscopic right hemicolectomy for right-sided colon cancer
Hongwei YAO ; Pengyu WEI ; Wenlong SHU ; Si WU ; Hanzheng ZHAO ; Jianning SONG ; Guocong WU ; Zhongtao ZHANG
Chinese Journal of Digestive Surgery 2024;23(6):770-774
Laparoscopic right hemicolectomy is currently the most commonly used surgical procedure for right-sided colon cancer. Although this procedure is maturing in terms of key tech-niques such as the extent of surgical resection, the extent of lymph node dissection, and the recons-truction of digestive tract, it still lacks a standardized surgical procedure and quality control system. In the pre-preparation phase of the COLOR Ⅳ study (an international, multicenter, randomized contro-lled trail comparing the efficacy of intracorporeal anastomosis versus extracorporeal anasto-mosis in laparoscopic right hemicolectomy for right-sided colon cancer), the research team of the authors formulates a standardized procedure for laparoscopic right hemicolectomy based on the Delphi survey, and develops a competency assessment tool for surgical ability and quality. Attempts are being made to automate the evaluation of surgical techniques using artificial intelligence. It is hoped that the above work will help colorectal surgeons to standardize surgical operations and reduce complications, provide support for the homogenization of multicenter clinical studies, and promote the implementation of structured training for this procedure.
4.Development of a basic palliative care competency assessment scale for generalist nurse and evaluation of its reliability and validity
Yuqi WU ; Lei LEI ; Huijuan MA ; Pengyu WANG ; Yu LUO
Journal of Army Medical University 2024;46(20):2337-2345
Objective To develop a basic competency assessment scale for generalist nurse in palliative care and test its reliability and validity.Methods The pre-test scale items pool was formed after literature review,internal discussion in the group,consultation with experts and small sample pre-survey. From January to March 2021,the pre-test scale was used to investigate 1000 nurses in various wards including internal medicine,surgery,emergency,obstetrics and gynaecology,and intensive care units.The results were analyzed by SPSS software and AMOS software to undertake item analysis,exploratory factor analysis and confirmatory factor analysis to develop the final scale.Results Five common factors and 37 entries were identified by factor analysis and explained 71.031% of the total variance.The Cronbach's α coefficient of the scale was 0.953,the split-half reliability and the test-retest reliability of the scale was 0.772 and 0.963.The confirmatory factor analysis model fitted well,with x2/df=2.57,root mean square error of approximation (RMSEA)=0.059,comparative fit index (CFI)=0.909,incremental fit index(IFI)=0.910,and Tucker-Lewis index(TLI)=0.901.Conclusion Our developed basic competency assessment scale for generalist nurse in palliative care has good reliability and validity,and can be used to evaluate the basic competency of palliative care for generalist nurses.
5.Gandou Bushen Decoction improves spermatogenesis and promotes spermatogenic cell proliferation in Wilson disease TX mice by activating testicular ERK signaling pathway
Miaozhu YIN ; Kuiyu CHEN ; Limin WU ; Pengyu JIANG ; Zhihui JI ; Nian ZHANG ; Huan ZHOU ; Hui HAN
Journal of Southern Medical University 2024;44(11):2063-2073
Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.
6.Analysis of clinical characteristics and the related factors to flare in patients with systemic lupus erythematosus
Pengyu WANG ; Yuan FENG ; Yan ZHANG ; Zhenbiao WU ; Jie LIU
Chinese Journal of Rheumatology 2024;28(2):99-105
Objective:To summarize the clinical characteristics and factors that may affect the flare of patients with systemic lupus erythematosus (SLE).Methods:A total of 300 patients with SLE who were treated with standard treatment in the outpatient clinic of the department of rheumatology and immunology of the Second Affiliated Hospital of Air Force Military Medical University of PLA, were enrolled, and the patients were divided into 24 patients in the complete response group, 40 cases in the no response group, 192 cases in the treatment response group, and 44 cases in the low disease activity group according to the response to treatment. The differences in clinical characteristics and survival rates between the groups were compared and analyzed. Comparisons of count data were made using analysis of variance (ANOVA), comparisons of measurement data were made using the chi-square test or the Fisher′s ecact test, and survival rates were expressed as Kaplan-Meier curves. Cox regression analysis was adapted to explore risk factors for flare in these patients.Results:A total of 300 patients were followed. With a median follow-up time of 18 (1, 36) months, a total of 42 patients experienced flare. The clinical characteristics of the four groups were compared, and there were significant differences in age ( F=4.39, P=0.005), the presence of lupus nephritis ( χ2=12.66, P=0.005), hemoglobin level ( F=2.73, P=0.044), NLR level( F=3.88, P=0.010), cystatin C level( F=3.11, P=0.027), anti-RNP antibody ( χ2=12.04, P=0.007), anti-Sm antibody ( χ2=8.33, P=0.040), anti-SSB antibody ( P=0.014), anti-nucleosome antibody ( P=0.014), and anti-ribosomal P protein antibody ( χ2=11.83, P=0.008). There was no significant difference in survival between the four groups. Cox analysis showed that the combination of other autoimmune diseases [ HR(95%CI)=3.23(1.58, 6.57), P=0.001], anti-Sm antibody [ HR(95%CI)=2.15(1.04, 4.43), P=0.038], and anti-RNP antibody [ HR(95%CI)=2.54(1.13, 5.68), P=0.023] were risk factors for flare in patients with SLE who could reach the treatment target. Conclusion:Patients with SLE with different treatment responses have different clinical features, and all treatment can significantly improve the recurrence rate no matter what level of response to treatment. Patients concurrent with other autoimmune diseases, positive anti-Sm antibodies, and positive anti-RNP antibodies are at highrisk of flare.
7.Effect of NLRP3 inflammatome in renal interstitial fibrosis induced by unilateral ureteral obstruction in rats and its mechanism
Yingxin RUAN ; Junya JIA ; Zhanfei WU ; Wenya SHANG ; Pengyu ZHANG
Journal of Jilin University(Medicine Edition) 2024;50(3):587-595
Objective:To discuss the effect of NOD-like receptor protein 3(NLRP3)inflammasome on the renal interstitial fibrosis in the unilateral ureteral obstruction(UUO)model rats,and to clarify its potential mechanism.Methods:Thirty healthy male Wistar rats were randomly divided into sham operation group(n=6)and UUO group(n=24).The rats in sham operation group underwent the dissection of the ureter without ligation,while the rats in UUO group were sacrificed on the 3rd,7th,and 14th days after operation,and based on the treatment duration,the rats were divided into UUO 3 d group(n=8),UUO 7 d group(n=8),and UUO 14 d group(n=8).HE staining and Masson staining were used to observe the pathomorphology of kidney tissue of the rats in various groups;reagent kits were used to detect the levels of malondialdehyde(MDA),activities of superoxide dismutase(SOD),and levels of hydroxyproline(HYP)in kidney tissue of the rats in various groups;immunohistochemistry method was used to detect the expression levels of α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)proteins in kidney tissue of the rats in various groups;Western blotting method was used to detect the expression levels of NLRP3 protein in kidney tissue of the rats in various groups.Results:The HE staining results showed significant tubular dilation,interstitial edema,and widening,with increased infiltration of inflammatory cells,and shedding of epithelial cells was seen in parts of the tubular lumina of the rats in UUO group.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);compared with UUO 3 d group and UUO 7 d group,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).The Masson staining results showed that in UUO group,there was evident infiltration of inflammatory cells in the renal interstitium and a noticeable increase in fibrotic tissue proliferation;with the increasing of duration of UUO,some tubular structures disappeared,and the interstitial widened further with gradually increasing collagen deposition,particularly at the corticomedullary junction.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);and compared with UUO 3 d and UUO 7 d groups,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).Compared with sham operation group,the levels of MDA in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05),and the SOD activities were significantly decreased(P<0.05).Compared with sham operation group,the levels of HYP in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the level of HYP in obstructed kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05).The immunohistochemistry results showed that compared with sham operation group,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significant increased(P<0.05);compared with UUO 3 d and UUO 7 d groups,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05);compared with sham operation group,the expression levels of TGF-β1 protein in renal tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the expression levels of TGF-β1 protein in the tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 14 d group were significantly decreased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of NLRP3 protein in kidney tissue of the rats in UUO 7 d and UUO 14 d groups were significantly increased(P<0.05).Conclusion:The NLRP3 inflammasome plays a critical role in renal fibrosis of the UUO rats,and its mechanism may be related to the increasing of oxidative stress and the increasing of expression level of TGF-β1 protein.
8.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
9.Gandou Bushen Decoction improves spermatogenesis and promotes spermatogenic cell proliferation in Wilson disease TX mice by activating testicular ERK signaling pathway
Miaozhu YIN ; Kuiyu CHEN ; Limin WU ; Pengyu JIANG ; Zhihui JI ; Nian ZHANG ; Huan ZHOU ; Hui HAN
Journal of Southern Medical University 2024;44(11):2063-2073
Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.
10.The relationship between mobile phone dependence and academic burden among junior middle school students in Guizhou Province
WU Rong, REN Pengyu, MA Chencui, ZHU Jintao, LUO Yuan, LEI Tinglian, YANG Xiantao, YAN Zheng
Chinese Journal of School Health 2023;44(4):558-562
Objective:
To explore the relationship between mobile phone dependence (MPD) and academic burden among junior middle school students in Guizhou Province, under the "double reduction" policy by using a multi level model, so as to provide a basis for preventing the occurrence of MPD.
Methods:
From December 2021 to January 2022, 7 868 students from grade 1 to grade 3 in 3 cities (prefecture) of Guizhou Province were selected by multi stage stratification random sampling method, and on site investigation was conducted by self compiled questionnaire and Self rating Questionnaire for Adolescent Problematic Mobile Phone Use(SQAPMPU). Using MLwiN 2.30 to fit a multi level model of the relationship between MPD and academic burden among junior middle school students.
Results:
The MPD detection rate of junior middle school students in Guizhou Province was 20.9%. The multi level model revealed that MPD of junior middle school students was clustered at the level of school and class ( χ 2= 1 565.32 , P <0.01), and high perceived academic pressure had a positive predictive effect on MPD among junior middle school students ( β =1.96). Homework duration ≥90 min/d at weekends had a negative predictive effect on MPD ( β =-0.55), while participation in off campus training on learning days had a positive predictive effect ( β =1.66)( P <0.05).
Conclusion
The MPD occurrence level is higher among junior middle school students in Guizhou Province. Perceived academic pressure, time spent on homework during weekends, off campus training and other academic burdens have an impact on MPD among junior middle school students, which should be a cause of concern for schools, families and social departments.


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