1.Study on the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep
Ming QIAO ; Yao ZHAO ; Yi ZHU ; Yexia CAO ; Limei WEN ; Yuehong GONG ; Xiang LI ; Juanchen WANG ; Tao WANG ; Jianhua YANG ; Junping HU
China Pharmacy 2026;37(1):24-29
OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets, followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established , and the zebrafish were treated with L. ruthenicum Murr. extract (LRME) at concentrations of 0.1, 0.2 and 0.4 mg/mL, respectively; 24 h later, behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 (IL-6), IL-1β, IL-10, tumor necrosis factor-α (TNF-α)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT)], and neurotransmitters [5- hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), glutamic acid (Glu), dopamine (DA), and norepinephrine (NE)] were measured. The protein expression levels of protein kinase B1 (AKT1), phosphorylated AKT1 (p-AKT1), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), sarcoma proto-oncogene,non-receptor tyrosine kinase (SRC), and heat shock protein 90α family class A member 1 (HSP90AA1) in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these, apigenin, naringenin and others were recognized as core active compounds, while AKT1, EGFR and others served as key targets; EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-, medium-, and high-dose groups were 54.60%, 69.03% and 77.97%, 开发。E-mail:hjp_yft@163.com respectively, while the inhibition ratios of locomotor distance were 0.57, 0.83 and 0.95, respectively. Compared with the model group, the number of resting counts, resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups (P<0.05). Neuronal damage in the brain was alleviated. Additionally, the levels of IL-6, IL-1β, TNF-α, MDA, Glu, DA and NE, as well as the protein expression levels of AKT1, p-AKT1, EGFR, SRC and HSP90AA1, were markedly reduced (P<0.05), while the levels of IL-10, SOD, GSH-Px, CAT, 5-HT and GABA, as well as Bcl-2 protein expression, were significantly elevated (P<0.05). CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects, and its specific mechanism may be related to the regulation of inflammatory responses, oxidative stress, neurotransmitter balance, and the EGFR tyrosine kinase inhibitor resistance signaling pathway.
2.Creation and Exploration of the"Organized Fill-in-the-Blank Format"Disci-pline Construction Model for Forensic Medicine in the New Era
Zhi-Wen WEI ; Hong-Xing WANG ; Jun-Hong SUN ; Hao-Liang FAN ; Hong-Liang SU ; Le-Le WANG ; Wen-Ting HE ; Zhe CHEN ; Jie ZHANG ; Xiang-Jie GUO ; Ji LI ; Geng-Qian ZHANG ; Xin-Hua LIANG ; Jiang-Wei YAN ; Qiang-Qiang ZHANG ; Cai-Rong GAO ; Ying-Yuan WANG ; Hong-Wei WANG ; Jun XIE ; Bo-Feng ZHU ; Ke-Ming YUN
Journal of Forensic Medicine 2025;41(1):25-29
Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.
3.Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
Ming XU ; Wenhao ZHU ; Siyu HOU ; Hongzhi XU ; Jingwen XIA ; Liyu LIN ; Hao FU ; Mingyu YOU ; Jiafeng WANG ; Zhi XIE ; Xiaohong WEN ; Yingwei WANG
Chinese Medical Journal 2025;138(17):2170-2179
BACKGROUND:
Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.
METHODS:
PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.
RESULTS:
PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.
CONCLUSIONS:
The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.
TRIAL REGISTRATION
ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Algorithms
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Lung Diseases/etiology*
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Machine Learning
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Neurosurgical Procedures/adverse effects*
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Postoperative Complications/diagnosis*
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Risk Factors
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ROC Curve
4.Complications among patients undergoing orthopedic surgery after infection with the SARS-CoV-2 Omicron strain and a preliminary nomogram for predicting patient outcomes.
Liang ZHANG ; Wen-Long GOU ; Ke-Yu LUO ; Jun ZHU ; Yi-Bo GAN ; Xiang YIN ; Jun-Gang PU ; Huai-Jian JIN ; Xian-Qing ZHANG ; Wan-Fei WU ; Zi-Ming WANG ; Yao-Yao LIU ; Yang LI ; Peng LIU
Chinese Journal of Traumatology 2025;28(6):445-453
PURPOSE:
The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery.
METHODS:
A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications.
RESULTS:
In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram.
CONCLUSION
Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans
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COVID-19/complications*
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Male
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Female
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Middle Aged
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Postoperative Complications/epidemiology*
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SARS-CoV-2
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Orthopedic Procedures/adverse effects*
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Aged
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Nomograms
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Adult
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Retrospective Studies
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Risk Factors
5.Current situation of clinical trial registration in acupuncture anesthesia: A scoping review.
Yue LI ; You-Ning LIU ; Zhen GUO ; Mu-En GU ; Wen-Jia WANG ; Yi ZHU ; Xiao-Jun ZHUANG ; Li-Ming CHEN ; Jia ZHOU ; Jing LI
Journal of Integrative Medicine 2025;23(3):256-263
BACKGROUND:
Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias.
OBJECTIVE:
Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP).
SEARCH STRATEGY:
We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics.
INCLUSION CRITERIA:
Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review.
DATA EXTRACTION AND ANALYSIS:
Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment.
RESULTS:
A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41).
CONCLUSION
The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans
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Acupuncture Analgesia
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Acupuncture Therapy
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Anesthesia
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Clinical Trials as Topic
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Registries
6.Evaluation of the Effects of Tianma Gouteng Decoction Combined with Magnesium Sulfate and Labetalol on Lowering Blood Pressure and Improving Hemorheology in Patients with Gestational Hypertension
Yuan-Yuan GENG ; Wei-Wei LIU ; Wen-Juan CAO ; Yan LI ; Xiao-Ming ZHU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):612-618
Objective To observe the effects of Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol on lowering blood pressure and improving hemorheology in patients with gestational hypertension.Methods Ninety patients with gestational hypertension of liver-yang hyperactivity type were randomly divided into the combination group and the control group,with 45 cases in each group.The control group was treated with magnesium sulfate combined with Labetalol,and the combination group was treated with Tianma Gouteng Decoction on the basis of treatment for the control group.The course of treatment lasted for 5 days.The changes of systolic blood pressure(SBP),diastolic blood pressure(DBP),urinary protein level,and hemorheological indicators of the two groups were observed before and after the treatment.Moreover,the adverse pregnancy outcomes,adverse reactions,and patients'satisfaction of the two groups were compared.Finally,the influencing factors of patients'adverse pregnancy outcomes were investigated by logistic regression analysis.Results(1)After treatment,the SBP,DBP and urinary protein level of patients in the two groups were significantly decreased compared with those before treatment(P<0.05),and the decrease in the combination group was significantly superior to that in the control group(P<0.01).(2)After treatment,the hemorheological indicators of plasma viscosity,whole blood viscosity and hematocrit of patients in the two groups were significantly decreased compared with those before treatment(P<0.05),and the decrease in the combination group was significantly superior to that in the control group(P<0.05 or P<0.01).(3)The total incidence of adverse pregnancy outcomes in the combination group was 11.11%(5/45),which was significantly lower and that in the control group(33.33%,15/45),the difference being statistically significant(P<0.05).(4)The patients'satisfaction of the combination group was 97.78%(44/45),which was significantly higher than that of the control group(84.44%,38/45),and the difference was statistically significant(P<0.05).(5)The total incidence of adverse reactions in the combination group was 13.33%(6/45)and that in the control group was 8.89%(4/45),but the intergroup comparison showed no significant difference between the two groups(P>0.05).(6)Logistic regression analysis of influencing factors showed that no medication of Tianma Gouteng Decoction combined with Labetalol and magnesium sulfate,and poor antihypertensive effect were the independent risk factors for adverse pregnancy outcomes in patients with gestational hypertension(all OR>1,P<0.05).Conclusion Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol in treating gestational hypertension exerts certain antihypertensive effect,and the therapy can effectively improve the hemorheological indicators and the adverse pregnancy outcomes,and enhance the patients'satisfaction.
7.Jianwei Xiaozhang Tablets Improves Precancerous Lesions of Gastric Cancer in Rats via Regulating PI3K-Akt-eNOS Pathway
Hai-Yang HUANG ; Shao-Wen ZHONG ; Yun AN ; Yu-Xin WANG ; Shu-Min ZHU ; Jie GAO ; Xiao-Min LU ; Ming-Guo DONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):709-718
Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P<0.01),splenic coefficient and hepatic coefficient were significantly decreased(P<0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P<0.01),the serum GAS content was significantly increased(P<0.01),and the MTL,GC contents were significantly reduced(P<0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P<0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P<0.01),and the protein expression level of VEGFA was reduced(P<0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P<0.05 or P<0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.
8.Preliminary construction of a measurement tool for atrial fibrillation patient's experience of catheter ablation
Ming-Li DU ; Song-Wen CHEN ; Li ZHU ; Xian-Feng YAO ; Lei YE ; Shao-Wen LIU
Fudan University Journal of Medical Sciences 2024;51(2):198-204
Objective To construct a measurement tool for atrial fibrillation(AF)patients'experience of catheter ablation,in order to provide quantifiable basis for improving the patients'perioperative experience.Methods From Jun 2022 to Apr 2023,literature analysis,qualitative research,Delphi expert consultation,and analytic hierarchy process were used to determine the content and weight of various indicators of the measurement tool.Results The enthusiasm of experts in 3 rounds was 100%.The authority coefficient of experts was 0.946,0.961 and 0.976.The Kendal harmony coefficients of the 2 and 3 rounds of expert consultation was 0.130 and 0.370(P<0.001).The final measurement tool included 46 items and 5 dimensions,including operational and technical quality experience,comfort management experience,information and communication experience,emotional support experience,service process and response experience.Conclusion The preliminary construction of measurement tool for AF patients'experience of catheter ablation,which were based on the features of specialty,could not only evaluate the patients'experience accurately,but also provide a basis for targeted improvement of medical and nursing service quality.
9.The prognostic significance and biological effects of CYP27A1 in hepatocellular carcinoma
Xin-Tong ZHANG ; Hao WU ; Yan-Fen HU ; Wen-Tao ZHANG ; Jing-Jia CHANG ; Jian-Jun ZHU ; Li LI ; Ming LIU
Medical Journal of Chinese People's Liberation Army 2024;49(4):387-395
Objective To analyze the prognostic significance and biological effects of cytochrome P450 family 27 subfamily A member 1(CYP27A1)in hepatocellular carcinoma(HCC),and to preliminarily explore its molecular mechanism of regulating the malignant growth of HCC.Methods The Cance Genome Atlas(TCGA)database was used to analyze the expression level of CYP27A1 and its prognostic effect on HCC patients.The samples were divided into CYP27A1 high-expression group(n=170)and low-expression group(n=170)based on the median expression of CYP27A1 in HCC,gene set enrichment analysis(GSEA)was performed to investigate gene sets associated with CYP27A1 expression.The subcellular localization of CYP27A1 was detected by immunofluorescence staining and search database.The over-expression plasmid of CYP27A1 was constructed and then transfected into the HCC cells MHCC-97H and HCCLM3 cell lines,including two groups,namely control group(transfecting empty vector)and CYP27A1 over-expression group(transfecting CYP27A1 over-expressed vector).CCK-8,flow cytometer,and reactive oxygen species(ROS)fluorescence probe were applied to detect the effects of CYP27A1 over-expression on cell viability,apoptosis and ROS levels in HCC cells.Combining bioinformatics to analyze the correlation between CYP27A1 and the expression of ROS generation-related genes and HCC proliferation-related genes.Results Compared with the normal liver tissue,the expression level of CYP27A1 mRNA in HCC tissue was significantly reduced(P<0.01).The expression of CYP27A1 was significantly correlated with sex,T stage,tumor grade and tumor stage of HCC patients(P<0.05).Compared to the CYP27A1 high-expression group,patients in CYP27A1 low-expression group had lower survival rate(P<0.01).GSEA enrichment analysis revealed that the levels of HCC stem cell-related gene clusters and HCC proliferation gene clusters were remarkably increased in CYP27A1 low-expression group.The immunofluorescence showed that CYP27A1 was mainly located in nucleus in MHCC-97H and HCCLM3,whereas CYP27A1 was mainly located in mitochondria in HepG2.CYP27A1 over-expression attenuated cell viability(P<0.01),and reduced the ROS levels(P<0.05),whereas it had no effects on the apoptosis in HCC cells(P>0.05).The expression of CYP27A1 and the expression of inhibiting ROS generation-related genes were positively correlated(P<0.05),while the expression of inhibiting ROS generation-related genes and the expression of HCC proliferation-related genes were negatively correlated(P<0.05).Conclusions The expression of CYP27A1 was decreased in HCC,and down-regulated CYP27A1 promoted cell growth by enhancing ROS generation,although the precise mechanism requires future educidation.
10.Analysis on genetic etiology of disorders of sex development using whole exome sequencing
Liu-Jiao WU ; Chan-Chan JIN ; Shu ZHU ; Wen-Ming HUANG ; Jian-Hong YE ; Tao LYU ; Bao-Sheng ZHU ; Jing HE
Medical Journal of Chinese People's Liberation Army 2024;49(5):495-503
Objective To elucidate the molecular genetic etiology of patients with disorders of sex development(DSD)using whole exome sequencing(WES),thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities.Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021,with an additional family study for one proband.Genomic DNA was extracted from patients for WES analysis.Single nucleotide polymorphism(SNP)and insertions/deletion(InDel)tests were identified using SAMtools software in conjunction with established SNP and InDel databases.Copy number variations(CNVs)at the exon level were detected using ExomeDepth,while the potential pathogenicity of mutations was predicted with PolyPhen-2,Mutation taster and PyMol software,with Sanger sequencing employed for confirmation.Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD.Among the 46,XX DSD patients,the SRY gene was detected in 14 patients.In the remaining 8 patients and a proband's families,single nucleotide site variations(SNVs)of NR5A1,PROKR2 and ANOS1 genes were identified in 2 patients,and CNVs in CYP21A2 gene were found in 4 patients.The pathogenicity of CYP21A2 EX1 Dup has been previously reported,while the remaining 3 CNVs were of uncertain significance,and no DSD-related mutations were detected in 2 patients.In the WES analysis of 46,XY DSD patients,10 pathogenic or likely pathogenic SNVs across 5 genes(SRY,AR,SRD5A2,CYP17A1,and NR5A1)were identified in 14 patients.Additionally,5 likely pathogenic CNVs involving the CYP21A2,AKR1C2,CBX2,and NR5A1 genes were detected in 5 patients,comprising 3 deletions and 2 duplications.Novel SNVs in NR5A1(c.722G>T,c.48C>G)and ANOS1 c.564A>T were identified,with no prior reports in relevant databases.The pathogenicity of CYP21A2 EX1 Dup is documented in related databases,while the remaining CNVs have not been previously reported.Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD,broadened the spectrum of known DSD-related gene mutations,and deepened our comprehension of DSD pathogenesis,offering valuable support for genetic counseling.

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