1.Construction and effectiveness evaluation of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy based on SWOT analysis
Jia WANG ; Weihong GE ; Ruijuan XU ; Shanshan QIAN ; Xuemin SONG ; Xiangling SHENG ; Bin WU ; Li LI
China Pharmacy 2025;36(4):401-406
OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy, and ensure the safety of drug use in patients. METHODS SWOT (strength, weakness, opportunity, threat) analysis method was used to analyze the internal strengths and weaknesses, as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital, and propose improvement strategies. RESULTS & CONCLUSIONS A refined, full-process, closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established, which is traceable in origin, trackable in destination, and accountable in responsibility. After the application of this system, the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020, the inventory volume decreased by 29.50% compared to the first quarter of 2020, the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020; the average workload per post in the same period of 2023 increased by 49.09% compared to 2019, the dispensing accuracy rate reached 100%, and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.
2.Analysis of factors associated with recurrence of macular edema secondary to branch retinal vein occlusion after anti-vascular endothelial growth factor treatment
Junmei WANG ; Shuna WANG ; Xuemin ZHANG ; Jianliang LIU ; Zhenhua FENG
International Eye Science 2025;25(9):1500-1504
AIM: To investigate the risk factors associated with the recurrence of macular edema secondary to branch retinal vein occlusion(BRVO-ME)after anti-vascular endothelial growth factor(anti-VEGF)therapy.METHODS:A total of 32 patients(32 eyes)with BRVO-ME who were treated at the ophthalmology department of the Affiliated Hospital of Shandong Second Medical University from February 2021 to June 2022 were selected. They were treated with a 3+pro re nata (PRN)anti-VEGF regimen and followed up for 6 mo. Following 3 consecutive anti-VEGF injections, patients were categorized into a non-recurrence group and a recurrence group based on central macular thickness(CMT)measured by optical coherence tomography(OCT)at 6 mo post-treatment. Aqueous humor levels of various cytokines levels were quantified using suspension assay method. Demographic characteristics, CMT, and cytokine levels were compared between the two groups, and their correlations with the recurrence of BRVO-ME after anti-VEGF treatment were analyzed.RESULTS:At 6 months post-treatment, ME resolved in 19 eyes(no recurrence group), while 13 eyes showed persistent or recurrent ME(recurrence group). Compared to baseline, the CMT significantly improved in both groups at 1 d, 1, and 6 mo post-treatment(all P<0.05). However, the recurrence group exhibited significantly higher baseline, 1 d and 6 mo post-treatment CMT values than the non-recurrence group(all P<0.05). The aqueous humor levels of VEGF and monocyte chemoattractant protein-1(MCP-1)at baseline were significantly higher in the recurrence group than the non-recurrence group(all P<0.05). Spearman correlation analysis revealed positive associations between baseline CMT and interlukin IL-1β, IL-5, IL-12, MCP-1 and IP-10 levels(all P<0.05). Multivariable Logistic regression analysis identified baseline CMT and MCP-1 levels as independent risk factors for BRVO-ME recurrence(OR>1, P<0.05).CONCLUSION: Elevated baseline CMT and aqueous humor MCP-1 levels were identified as independent risk factors for BRVO-ME recurrence after anti-VEGF therapy. Patients exhibiting higher baseline CMT and MCP-1 levels demonstrated significantly increased susceptibility to recurrence.
3.Expert consensus on the prevention and treatment of radiochemotherapy-induced oral mucositis.
Juan XIA ; Xiaoan TAO ; Qinchao HU ; Wei LUO ; Xiuzhen TONG ; Gang ZHOU ; Hongmei ZHOU ; Hong HUA ; Guoyao TANG ; Tong WU ; Qianming CHEN ; Yuan FAN ; Xiaobing GUAN ; Hongwei LIU ; Chaosu HU ; Yongmei ZHOU ; Xuemin SHEN ; Lan WU ; Xin ZENG ; Qing LIU ; Renchuan TAO ; Yuan HE ; Yang CAI ; Wenmei WANG ; Ying ZHANG ; Yingfang WU ; Minhai NIE ; Xin JIN ; Xiufeng WEI ; Yongzhan NIE ; Changqing YUAN ; Bin CHENG
International Journal of Oral Science 2025;17(1):54-54
Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans
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Chemoradiotherapy/adverse effects*
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Consensus
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Risk Factors
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Stomatitis/etiology*
4.Review of Astragalus membranaceus polysaccharides: Extraction process, structural features, bioactivities and applications.
Hongyue TIAN ; Lingzhuo AN ; Pengwang WANG ; Xuemin ZHANG ; Wenyuan GAO ; Xia LI
Chinese Herbal Medicines 2025;17(1):56-69
Astragalus membranaceus possesses the function of enhancing immunity, protecting the liver, diuretic, anti-aging, anti-stress, anti-hypertensive, and more extensive antibacterial effects. Polysaccharides, one kind of the major active ingredients of A. membranaceus, are considered to be responsible for their versatile use. Now, a systematic summary of research progress and prospects of polysaccharides from A. membranaceus polysaccharides (AMPs) is necessary to facilitate their further study and application. In this review, the optimal extraction methods, structural features, biological activities, and applications of AMPs were emphasized. The structure-activity relationships are also analyzed and elucidated. Solvent, ultrasonic, microwave, enzyme-assisted, ultra-high pressure, and combined methods have been used to extract AMPs. Among them, solvent extraction is the most commonly used method because it is simple and easy to operate, but the efficiency needs to be improved further. The ultra-high pressure method is the most efficient but has a low economic return. AMPs exhibited various bioactivities, including immunomodulation, antitumor, and antidiabete. The structure-activity relationships revealed that different structure configurations, chain conformations, and physical properties would have different bioactivities. However, the new method for purification of certain polysaccharides, detailed structure-activity relationships (SAR), mechanisms of bioactivities, and quality control of AMPs need to be extensively investigated.
5.miR-411-3p attenuates silica-induced pulmonary fibrosis in mice by suppressing alveolar type II epithelial-mesenchymal transition via targeting SMURF2 regulation
Siyi WANG ; Jiakun DU ; Siyuan SHAN ; Bingbing LI ; Xinyu WANG ; Zhongqiu WEI ; Hong XU ; Xuemin GAO
Journal of Environmental and Occupational Medicine 2025;42(12):1438-1445
Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO2) (200 mg·mL-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO2 group, (2) SiO2+negative control siRNA (siRNA-NC) group and SiO2+Smurf2 gene silencing (si-Smurf2) group, (3) SiO2+solvent (DMSO) group and SiO2+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO2+miR-NC group and SiO2+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO2-induced MLE-12 cells, compared to the control group, the SiO2-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO2, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO2 group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.
6.Relationship between hand and wrist bone age assessment method and application to male children
Zhen BIAN ; Yuan GUO ; Xuemin LYU ; Naijun WAN ; Qianqian WANG ; Zheng YANG
Chinese Journal of Surgery 2024;62(12):1136-1142
Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.
7.Medication Patterns of Chinese Medicines for Neurodermatitis Based on Contemporary Medical Cases
Shuguang CHEN ; Xuemin WANG ; Fanghong DUAN ; Lele CHEN ; Jialin TENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):206-213
ObjectiveTo mine the medication patterns of Chinese medicines for neurodermatitis based on contemporary medical cases in published articles. MethodThe medical cases of treating neurodermatitis with Chinese medicines were retrieved from the medical case articles published by contemporary famous and old Chinese medicine doctors in the library of Shandong University of Traditional Chinese Medicine, CNKI, VIP, and Wanfang Data. A case library was established, and SPSS Statistics 26.0 and SPSS Modeler 18.0 were employed to analyze the symptoms and syndromes of neurodermatitis and mine the medication patterns. ResultAccording to the inclusion and exclusion criteria, 130 medical case articles were included in this study. Neurodermatitis was prevalent in young adults between 20 and 39 years old (female patients of 30-49 years old and male patients of 20-39 years old), and male patients were more than female patients. The patients mainly presented the clinical manifestations of itchy rashes, thickened skin, and lichenification. Symptoms included skin injury, emotional abnormalities, and Yin damage caused by prolonged illness. Red tongue, thin white or yellow tongue coating, and wiry pulse were common in the patients. The patients with the syndrome of blood deficiency and wind dryness were often treated with Angelicae Sinensis Radix, Rehmanniae Radix, Glycyrrhizae Radix et Rhizoma, Tribuli Fructus, and Chuanxiong Rhizoma. The commonly used herb pairs included Chuanxiong Rhizoma-Paeoniae Radix Alba, Chuanxiong Rhizoma-Glycyrrhizae Radix et Rhizoma, and Rehmanniae Radix Praeparata-Saposhnikoviae Radix, and the commonly used prescriptions were Siwutang and Dangguiyinzi. The patients with the syndrome of muscle and skin dystrophy were mainly treated with Rehmanniae Radix, Sophorae Flavescentis Radix, Paeoniae Radix Alba, Tribuli Fructus, and Dictamni Cortex. The commonly used herb pairs included Polygoni Multiflori Caulis-Sophorae Flavescentis Radix, Polygoni Multiflori Caulis-Dictamni Cortex, and Salviae Miltiorrhizae Radix et Rhizoma-Paeoniae Radix Alba, and the commonly used prescriptions were Jingjie Siwutang and Baixianpiyin. The patients with the syndrome of liver depression transforming into fire were often treated with Rehmanniae Radix, Gentianae Radix et Rhizoma, Gardeniae Fructus, Bupleuri Radix, and Scutellariae Radix. The commonly used herb pairs included Gentianae Radix et Rhizoma-Polygoni Multiflori Caulis, Polygoni Multiflori Caulis-Gardeniae Fructus, and Gentianae Radix et Rhizoma-Saposhnikoviae Radix, and the commonly used prescriptions were Longdan Xiegantang and Danzhi Xiaoyaosan. ConclusionThis study enriches the knowledge about neurodermatitis, clarifies the treatment principles and methods as well as the medication patterns, and provides a theoretical basis for clinical treatment and medication based on syndrome differentiation.
8.GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis.
Xuezhi YANG ; Yingjie ZHAO ; Qi WEI ; Xuemin ZHU ; Luping WANG ; Wankang ZHANG ; Xiaoyi LIU ; Jiajie KUAI ; Fengling WANG ; Wei WEI
Acta Pharmaceutica Sinica B 2024;14(1):241-255
Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.
9.Exploration of prognostic factors and nomogram construction for advanced non-small cell lung cancer treated with immunotherapy based on hematologic indexes
Weiwei SUN ; Xuemin YAO ; Pengjian WANG ; Jing WANG ; Jinghao JIA
Journal of International Oncology 2024;51(3):143-150
Objective:To explore influencing factors affecting the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy based on hematologic indexes, thus to construct and evaluate a nomogram prediction model.Methods:The clinical data of 80 patients with advanced NSCLC treated with programmed death-1 inhibitor monotherapy or combination regimen from January 2018 to June 2020 at the Affiliated Hospital of North China University of Science and Technology and Tangshan People's Hospital were retrospectively analyzed. Hematologic indexes at the baseline, the optimal remission and the progressive disease (PD) were collected separately, and independent influencing factors for patient prognosis were analyzed using Cox proportional hazards regression model. A nomogram prediction model was constructed based on the results of the multifactorial analysis, and the predictive performance of the model was evaluated by receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curves.Results:As of the follow-up cut-off date, of the 80 patients, 63 had PD, with a median overall survival (OS) of 16.9 months. Univariate analysis showed that, age ( HR=2.09, 95% CI: 1.17-3.74, P=0.013) , number of treatment lines ( HR=2.23, 95% CI: 1.21-4.12, P=0.010) , lymphocyte to monocyte ratio (LMR) at the baseline ( HR=0.75, 95% CI: 0.57-0.97, P=0.028) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) and lactate dehydrogenase (LDH) ( HR=1.01, 95% CI: 1.00-1.01, P=0.006) at the optimal remission, haemoglobin ( HR=0.97, 95% CI: 0.96-0.99, P<0.001) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) , C-reactive protein ( HR=1.01, 95% CI: 1.00-1.01, P=0.011) , albumin (ALB) ( HR=0.91, 95% CI: 0.87-0.96, P=0.001) , neutrophil to lymphocyte ratio (NLR) ( HR=1.16, 95% CI: 1.05-1.27, P=0.002) and LMR ( HR=0.62, 95% CI: 0.42-0.90, P=0.012) at the PD were all influencing factors for the prognosis of advanced NSCLC patients receiving immunotherapy. Least absolute shrinkage and selection operator regression were used to screen the variables for P<0.10 in the univariate analysis, and nine possible influencing factors were obtained, which were age, fibrinogen and LDH at the optimal remission, haemoglobin, D-dimer, C-reactive protein, LDH, ALB and LMR at the PD. Multivariate analysis of the above variables showed that, age ( HR=0.91, 95% CI: 0.86-0.97, P=0.004) , LDH ( HR=1.01, 95% CI: 1.00-1.01, P=0.013) and ALB ( HR=0.82, 95% CI: 0.67-0.99, P=0.041) at the PD were independent influencing factors for the prognosis of patients with advanced NSCLC who received immunotherapy. The area under curve of the nomogram predicting model based on the above indexes, 1- and 2-year OS rates of patients were 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.66-0.88) , respectively, and C-index was 0.71 (95% CI: 0.64-0.78) , the calibration curves showed good consistency between predicted and actual probability of occurrence. Patients in the low-risk group ( n=40) had a median OS of 29.9 months (95% CI: 22.5 months-NA) , which was significantly better than that of the high-risk group ( n=40) [13.4 months (95% CI: 11.4-23.5 months) , χ2=11.30, P<0.001]. Conclusion:Age, LDH and ALB at the PD are independent influencing factors affecting the prognosis of patients with advanced NSCLC receiving immunotherapy, and the nomogram model constructed based on the above indexes has good differentiation and calibration for predicting 1- and 2-year OS rates in advanced NSCLC patients receiving immunotherapy.
10.The role of virtual reality simulation training in laparoscopic skills training for young physicians
Liming SONG ; Lu WANG ; Xibin DUAN ; Chao MA ; Xuemin LI ; Ningwei YIN ; Zhongzhen WANG
Chinese Journal of Medical Education Research 2024;23(3):396-400
Objective:To explore the significance of laparoscopic virtual reality simulation training by analyzing the learning curve of laparoscopic cholecystectomy among young general surgeons who had participated in laparoscopic skills training at our hospital.Methods:Fifty young surgeons were divided into two groups, with the intervention group participating in virtual reality simulation training and the control group participating in traditional laparoscopic clinical training. After completion of the training, 30 laparoscopic cholecystectomies were performed under the supervision of highly qualified surgeons with extensive laparoscopic experience. CUSUM analysis was applied to plot the trainees' surgical learning curve based on the completion rate, surgical score and operative time. " x" is the number of surgical cases and " k" is the slope. The value of x when k=0 was calculated and the surgical learning curves and intraoperative scores of the 2 groups of trainees were compared. SPSS 23.00 was performed for t-test and Chi-square test. Results:The intervention and control groups crossed the surgical learning curve at x=19.24±0.39 and x=21.72±0.73 respectively, with significant differences ( P<0.01); the intervention and control groups scored (10.82±2.73) and (9.71±2.69) for gallbladder exposure ( t=4.61, P<0.01), (12.59±3.12) and (8.87±2.99) for gallbladder dissection triangle ( t=6.21, P<0.01), and (10.69±3.38) and (8.80±3.55) for gallbladder dissection ( t=3.10, P<0.01). Conclusions:Virtual reality simulation training can facilitate the translation of basic laparoscopic training skills into clinical skills and can promote the growth of young general surgeons.

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