1.Lichong Xiaozheng Granules enhances cisplatin sensitivity of ovarian cancer xenografts in rats by regulating adenine nucleotide translocator 3-mediated mitochondrial apoptosis.
Yiliu CHEN ; Min MA ; Ran SU ; Yinbin ZHU ; Qing FENG ; Jiali LUO ; Weifeng FENG ; Xianxin YAN
Journal of Southern Medical University 2025;45(11):2309-2319
OBJECTIVES:
To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment.
METHODS:
LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.
RESULTS:
A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.
CONCLUSIONS
LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals
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Female
;
Cisplatin/pharmacology*
;
Ovarian Neoplasms/metabolism*
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Apoptosis/drug effects*
;
Mitochondria/metabolism*
;
Drugs, Chinese Herbal/pharmacology*
;
Mice, Inbred BALB C
;
Mice
;
Rats
;
Xenograft Model Antitumor Assays
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Humans
;
Cell Line, Tumor
;
Antineoplastic Agents/pharmacology*
2.Pathogenesis of Idiopathic Pulmonary Fibrosis and Modulating Effect of Chinese Medicine: A Review
Enguo ZOU ; Tianyu HUANG ; Mulan WANG ; Chenliang ZHA ; Qin GONG ; Weifeng ZHU ; Yulin FENG ; Liangji LIU ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):280-289
Idiopathic pulmonary fibrosis (IPF), as a progressive lung disease, has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs, which are ineffective and induce side effects, failing to meet the clinical needs. Therefore, developing safer and more effective drugs has become an urgent task, which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization, epithelial-mesenchymal transition (EMT), oxidative stress, and autophagy, while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory, Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore, the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood, warming Yang and tonifying Qi, and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization, restoring redox balance, inhibiting EMT, and regulating cell autophagy. However, few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field, we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines, we focus on exploring systemic treatment options for IPF, with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.
3.The value of urine protein kinase Y-linked gene promoter site methylation in early diagnosis of prostate cancer
Weifeng LIU ; Zheng DAI ; Yibin ZHOU ; Kaiwen FENG ; Kai WEI ; Gule SUN ; Dongrong YANG ; Jin ZHU
The Journal of Practical Medicine 2024;40(5):688-694
Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.
4.Community pediatric services under the family physician team model
Wenwen WANG ; Feng XIAO ; Miao WANG ; Daoliang YANG ; Weifeng LU
Chinese Journal of General Practitioners 2024;23(2):176-180
Childhood is an important period for individual health. In order to provide community child health services, Zhoujiaqiao Community Health Service Center of Shanghai Changning District has opened a pediatric clinic since July 2017. Through equipping basic facilities, personnel training, extending service items and service time, allocating resources with cooperative hospitals, optimizing internal system management and other methods, the community pediatric service under the family physician team model has been initially constructed. The article summarizes experiences in the construction and operation of community pediatric services and child health care, to provide reference for the development of a replicable and promotable urban community pediatric service system under the contracted family physician team model.
5.Differential component analysis between Fructus Tritici Levis and Triticum aestivum based on qualitative and quantitative methods
Xuejiao LI ; Yu HU ; Yun CHEN ; Juan SHANG ; Zhenyang LI ; Yunhua FENG ; Jiandong ZOU ; Weifeng YAO ; Su LU ; Meijuan XU
China Pharmacy 2024;35(11):1296-1302
OBJECTIVE To analyze the compositional differences between Fructus Tritici Levis and Triticum aestivum, and to provide reference for identification and quality control of both. METHODS Twenty batches of Fructus Tritici Levis and three batches of T. aestivum were collected, and their fingerprints were acquired by high-performance liquid chromatography and the similarities were evaluated by the Evaluation System of Similarity of Chromatographic Fingerprints of Traditional Chinese Medicine (2012 version). Cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to analyze the difference of Fructus Tritici Levis and T. aestivum from different regions, and the differential components were screened. The contents of the six identified components in Fructus Tritici Levis and T. aestivum were determined. RESULTS The similarities of the fingerprints of Fructus Tritici Levis ranged from 0.928 to 0.996, and the relative similarities of T. aestivum with Fructus Tritici Levis ranged from 0.761 to 0.773. A total of 19 common peaks were calibrated, and six components including linolenic acid, linoleic acid, 5-heptadecylresorcinol, 5-nonadodecylresorcinol, 5- heneicosylresorcinol, and 5-tricosylresorcinol were identified. The results of CA and PCA showed that Fructus Tritici Levis and T. aestivum could be clearly distinguished; the distribution of Fructus Tritici Levis from Anhui province was relatively concentrated. The results of OPLS-DA showed that linolenic acid, linoleic acid, and other six unknown compounds were the differential components between Fructus Tritici Levis and T. aestivum. The average contents of the six identified components in Fructus Tritici Levis were 0.100 9, 1.094 0, 0.005 1, 0.030 9, 0.098 2,and 0.024 8 mg/g, respectively; the contents of linolenic acid and linoleic acid in Fructus Tritici Levis were significantly higher than those in T. aestivum (P<0.05).CONCLUSIONS The established qualitative and quantitative methods are simple and reliable, and can be used for the identification and quality evaluation of Fructus Tritici Levis and T. aestivum. The identified differential components, such as linolenic acid and linoleic acid, can also provide clues for the differentiation and pharmacological study of Fructus Tritici Levis and T. aestivum.
6.Differential component analysis between Fructus Tritici Levis and Triticum aestivum based on qualitative and quantitative methods
Xuejiao LI ; Yu HU ; Yun CHEN ; Juan SHANG ; Zhenyang LI ; Yunhua FENG ; Jiandong ZOU ; Weifeng YAO ; Su LU ; Meijuan XU
China Pharmacy 2024;35(11):1296-1302
OBJECTIVE To analyze the compositional differences between Fructus Tritici Levis and Triticum aestivum, and to provide reference for identification and quality control of both. METHODS Twenty batches of Fructus Tritici Levis and three batches of T. aestivum were collected, and their fingerprints were acquired by high-performance liquid chromatography and the similarities were evaluated by the Evaluation System of Similarity of Chromatographic Fingerprints of Traditional Chinese Medicine (2012 version). Cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to analyze the difference of Fructus Tritici Levis and T. aestivum from different regions, and the differential components were screened. The contents of the six identified components in Fructus Tritici Levis and T. aestivum were determined. RESULTS The similarities of the fingerprints of Fructus Tritici Levis ranged from 0.928 to 0.996, and the relative similarities of T. aestivum with Fructus Tritici Levis ranged from 0.761 to 0.773. A total of 19 common peaks were calibrated, and six components including linolenic acid, linoleic acid, 5-heptadecylresorcinol, 5-nonadodecylresorcinol, 5- heneicosylresorcinol, and 5-tricosylresorcinol were identified. The results of CA and PCA showed that Fructus Tritici Levis and T. aestivum could be clearly distinguished; the distribution of Fructus Tritici Levis from Anhui province was relatively concentrated. The results of OPLS-DA showed that linolenic acid, linoleic acid, and other six unknown compounds were the differential components between Fructus Tritici Levis and T. aestivum. The average contents of the six identified components in Fructus Tritici Levis were 0.100 9, 1.094 0, 0.005 1, 0.030 9, 0.098 2,and 0.024 8 mg/g, respectively; the contents of linolenic acid and linoleic acid in Fructus Tritici Levis were significantly higher than those in T. aestivum (P<0.05).CONCLUSIONS The established qualitative and quantitative methods are simple and reliable, and can be used for the identification and quality evaluation of Fructus Tritici Levis and T. aestivum. The identified differential components, such as linolenic acid and linoleic acid, can also provide clues for the differentiation and pharmacological study of Fructus Tritici Levis and T. aestivum.
7.Magnifying endoscopy combined with narrow-band imaging,acetate-indigo rouge staining combined with multi-slice spiral CT in the diagnosis of early gastric cancer and precancerous lesions and clinical significance
Liang YANG ; Zhihua FENG ; Weiling MA ; Weifeng MA ; Shuai CHEN ; Lixia ZHANG ; Jihai WU
China Journal of Endoscopy 2024;30(2):9-16
Objective To analyze the diagnostic efficacy and clinical significance of magnifying endoscopy combined with narrow-band imaging(ME-NBI),acetate-indigo rouge staining and multi-slice spiral CT for early gastric cancer and precancerous lesions.Methods 202 patients with suspected early gastric cancer and precancerous lesions from February 2019 to March 2022 were regarded as the subjects of this study,all the patients underwent ME-NBI,acetate-indigo rouge staining,and multi-slice spiral CT examination;The diagnostic value of different examination methods for early gastric cancer and precancerous lesions was analyzed using the receiver operator characteristic curve(ROC curve),using the pathological results of gastric cancer as the gold standard,the diagnostic value of ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT and their combination in early gastric cancer and precancerous lesions was analyzed using a four grid table.Results The image quality of ME-NBI and acetate-indigo rouge staining combined examinations was significantly higher than that of their respective independent examinations(P<0.05).There was significant difference in the degree of differentiation in the clinical features of patients with early gastric cancer and precancerous lesions(P<0.05).The area under the curve(AUC)of ME-NBI for the diagnosis of early gastric cancer and precancerous lesions was 0.853,the accuracy was 85.64%,the sensitivity was 88.37%,and the specificity was 83.62%.The AUC of acetate-indigo rouge staining for the diagnosis of early gastric cancer and precancerous lesions was 0.814,the accuracy was 81.68%,the sensitivity was 83.72%,and the specificity was 80.17%.The AUC of multi-slice spiral CT for the diagnosis of early gastric cancer and precancerous lesions was 0.804,with an accuracy of 80.69%,a sensitivity of 82.56%,and a specificity of 79.31%.And the AUC of the three methods combined to diagnose early gastric cancer and precancerous lesions was 0.893,with an accuracy of 89.60%,a sensitivity of 93.02%,and a specificity of 87.07%.Conclusion ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT has high diagnostic efficacy in early gastric cancer and precancerous lesions,and can be used in clinical practice.
8.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.
9.Analysis of factors influencing the efficacy and prognosis of surgical treatment for primary malignant pelvic bone tumors
Weifeng LIU ; Lin HAO ; Zhuoyu LI ; Tao JIN ; Yang SUN ; Yongkun YANG ; Yuan LI ; Fajun YANG ; Feng YU ; Qing ZHANG ; Xiaohui NIU
Chinese Journal of Oncology 2024;46(4):344-353
Objective:To analyze the prognostic factors and the influence of surgical margin to prognosis.Methods:A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models.Results:There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection ( P<0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection ( P<0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection ( P<0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions:The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.
10.Prognostic analysis in computer-assisted naviagtion for pelvic chondrosarcoma surgery
Zhuoyu LI ; Weifeng LIU ; Zhiping DENG ; Tao JIN ; Yuan LI ; Xieyuan JIANG ; Feng YU ; Qing ZHANG ; Xiaohui NIU
Chinese Journal of Orthopaedics 2024;44(10):676-684
Objective:To explore the effects of computer-navigated surgery and traditional surgery on the functional and oncological outcomes of pelvic chondrosarcoma.Methods:Retrospective analysis of 136 cases of pelvic chondrosarcoma surgically treated at Beijing Jishuitan Hospital from January 2000 to December 2017. There were 65 males and 71 females with an average age of 46.07±13.37 years (range 13-73 years). There were 120 primary cases and 16 secondary cases, of which 109 cases were ordinary chondrosarcoma (7 cases with pathological differentiation grade I, 83 cases with grade II. There were 109 cases of common type chondrosarcoma (7 cases of pathological differentiation grade I, 83 cases of grade II, 19 cases of grade III), 21 cases of dedifferentiated chondrosarcoma, 3 cases of mesenchymal type, 2 cases of clear cell type, 1 case of mucinous type; 12 cases of malignant degeneration of multilocular chondrosarcoma of bone; 104 cases of Enneking staging stage IB, 32 cases of stage IIB. According to the pelvis zone classification, there were 14 cases of pelvic zone I, 1 case of zone II, 13 cases of zone III, 16 cases of zone I+II, 16 cases of zone I+IV, 47 cases of zone II+III, 25 cases of zone I+II+III, 25 cases of zone I+II+III, 4 cases of zone I + II + III + IV. All cases were classified as intracapsular, marginal, or wide resection according to the resection boundary classification. There were 45 cases in computer-navigated surgery (navigated group) and 91 cases in non-navigated surgery group. The demographic data, preoperative tumor staging, surgical characteristics, surgical boundary classification, oncological indexes, reconstruction methods, postoperative complications, and bone and soft tissue tumor function score (Musculoskeletal Tumor Society score, MSTS) were compared between the two groups.Results:No surgical complications related to the computerized navigation system occurred in the navigation group. The postoperative follow-up time was 68.56±37.82 months (range 6-197 months) and 76.85±52.60 months (range 5-225 months) for the navigation and non-navigation groups, respectively. The MSTS was 25.43±2.85 and 24.56±4.19 points in the navigation and non-navigation groups, respectively, with no significant difference ( t=1.191, P=0.237). There were 10 cases of marginal resection and 35 cases of wide resection in the navigation group, and 12 cases of intracapsular resection, 32 cases of marginal resection and 47 cases of wide resection in the non-navigation group with significant difference (χ 2=10.977, P=0.004). There were 4 cases (8.9%, 4/45) of local recurrence after surgery in the navigation group and 20 cases (21.9%, 20/91) in the non-navigation group, with significant difference (χ 2=4.040, P=0.046). There were 2 cases of final amputation and 2 cases of re-excision with recurrence in the navigation group and 6 cases of final amputation and 14 cases of re-excision in the non-navigation group. Distant metastases occurred in 3 cases (7%, 3/45) in the navigation group and 18 cases (20%, 18/91) in the non-navigation group wtih significant difference (χ 2=4.478, P=0.034). The five-year postoperative survival rates of the navigation and non-navigation groups were 93.3% and 72.6%, and the three- and five-year progression-free survival rates were 91.1% and 84.4% and 74.8% and 62.7%, respectively, with significant differences (χ 2=5.081, P=0.024; χ 2=6.800, P=0.009). The five-year survival rate of stage IB tumors was 96.7% in the navigation group and 84.5% in the non-navigation group with significant difference (χ 2=3.897, P=0.048); the five-year survival rate of stage IIB tumors was 75.0% in the navigation group and 35.0% in the non-navigation group with no significant difference ( P>0.05). Postoperative complications included 15 cases of postoperative infection, 16 cases of deep vein thrombosis, 14 cases of double lower limb inequality, 2 cases of prosthesis dislocation, 2 cases of lymphedema, 1 case of hernia and 1 case of allograft bone resorption. There was no significant difference of complication rates between the two groups ( P>0.05). Conclusion:Computer navigation-assisted resection of pelvic chondrosarcoma was better in obtaining a safe surgical border of the tumor compared with traditional surgery, reducing the rate of local recurrence of the tumor and thus effectively improved the survival and prognosis of patients.

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