1.Bisdemethoxycurcumin suppresses liver fibrosis-associated hepatocellular carcinoma via inhibiting CXCL12-induced macrophage polarization.
Wei YUAN ; Xinxin ZENG ; Bin CHEN ; Sihan YIN ; Jing PENG ; Xiong WANG ; Xingxing YUAN ; Kewei SUN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(10):1232-1247
Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals
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Liver Neoplasms/etiology*
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Humans
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Carcinoma, Hepatocellular/immunology*
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Liver Cirrhosis/complications*
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Macrophages/drug effects*
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Male
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Rats
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Chemokine CXCL12/genetics*
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Diarylheptanoids/pharmacology*
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Rats, Sprague-Dawley
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beta Catenin/genetics*
2.Clinical features and traditional Chinese medicine syndrome distribution of treatment-naïve patients with hepatitis B virus-related primary liver cancer: An analysis of 99 cases
Tao TIAN ; Kewei SUN ; Xiong WANG ; Xinru LIU ; Weitao ZENG ; Wei YUAN
Journal of Clinical Hepatology 2025;41(11):2336-2342
ObjectiveTo investigate the clinical features and traditional Chinese medicine (TCM) syndrome distribution of treatment-naïve patients with hepatitis B virus-related primary liver cancer (HBV-PLC), and to provide a basis for integrated traditional Chinese and Western medicine in the prevention and treatment of HBV-PLC. MethodsA retrospective analysis was performed for the clinical data of 99 treatment-naïve HBV-PLC patients who were admitted to Department of Hepatology and Infectious Diseases in The First Affiliated Hospital of Hunan University of Chinese Medicine from January 2019 to December 2024. According to whether the patient received standardized antiviral therapy (for ≥3 years), they were divided into antiviral group and non-antiviral group, and according to the status of HBeAg, they were divided into HBeAg-positive group and HBeAg-negative group. Demographic features, laboratory test results, imaging data, and TCM syndrome data were collected, and neutrophil-to-lymphocyte ratio (NLR), Child-Pugh score, and CNLC stage were calculated. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. ResultsThe 99 treatment-naïve HBV-PLC patients had a mean age of 57.12±11.60 years, and the patients aged 50 — 75 years accounted for the highest proportion of 72.7%, with a male/female ratio of 5.2∶1. The patients with liver cirrhosis accounted for 81.8%, and 67.7% of the patients did not receive antiviral therapy in the past. The positive rates of HBV DNA, HBeAg, and alpha-fetoprotein were 80.8%, 18.2%, and 69.7%, respectively, and the patients with Child-Pugh class A/B disease accounted for 89.9%. Compared with the non-antiviral group, the antiviral group had a significantly smaller maximum tumor diameter (t=2.310, P=0.024), a significantly lower HBV DNA positive rate (χ2=14.006, P<0.001), and a significantly lower number of tumor thrombi (χ2=7.347, P=0.007). In addition, there were significant differences between the HBeAg-negative group and the HBeAg-positive group in Child-Pugh class (χ2=6.780, P=0.034) and CNLC stage (χ2=8.746, P=0.033). Among the 99 treatment-naïve HBV-PLC patients, 41.4% had liver depression and spleen deficiency with blood stasis, 22.2% had Qi deficiency and blood stasis syndrome, and 19.2% had damp-heat accumulation with blood stasis. ConclusionTreatment-naïve HBV-PLC patients are mainly middle-aged and elderly male individuals, and most of the patients are comorbid with liver cirrhosis. Standardized antiviral therapy can significantly reduce tumor burden and improve virologic response, with better hepatic compensation in HBeAg-negative patients, and hypoproteinemia is more common in patients with Qi deficiency and blood stasis syndrome.
3.Relationship between self-perceived noise intensity and sleep quality in noise-exposed workers—A mediating role of negative emotions
Li WANG ; Lei HUANG ; Jingxuan MA ; Kewei ZENG ; Juan WANG ; Yajia LAN
Journal of Environmental and Occupational Medicine 2024;41(5):519-525
Background Studies on the relationships of environmental noise exposure with negative emotions and sleep quality have long been reported. Self-perceived noise intensity is not only related to environmental noise exposure, but also reflects an individual's susceptibility to noise; however, few studies on self-perceived noise intensity, negative emotions, and sleep quality have been reported, and it is not clear whether negative emotions play a mediating role in the relationship between self-perceived noise intensity and sleep quality. Objective To analyze the mediating role of negative emotions (anxiety, depression, and stress) in the relationship between self-perceived noise intensity and sleep quality in noise-exposed workers, and to provide a scientific basis for addressing psychological problems and sleep quality induced by noise exposure. Methods Stratified cluster sampling was used to select noise-exposed workers from a large equipment manufacturing plant in Chengdu from May to June 2023, and demographic characteristics were investigated using a self-designed general information questionnaire; self-perceived noise intensity was reported by the study subjects as the noise intensity of their workplaces; sleep quality was synthesized from three indicators: night sleep duration, self-perceived sleep quality, and sleep-related symptoms; the Anxiety-Depression-Stress Scale (DASS-21 scale) was used to evaluate anxiety, depression, and stress of a worker. Structural equation modeling was used to analyze the pathways of negative emotions (anxiety, depression, and stress) between self-perceived noise intensity and sleep quality. Results The positive rates of negative emotions were 33.1% (anxiety symptoms, 215/649), 26.0% (depression symptoms, 169/649), and 14.0% (stress symptoms, 91/649), respectively in a total of 649 noise-exposed workers. Self-perceived noise intensity was positively correlated with sleep quality score (r=0.218, P<0.001) and negative emotions (anxiety, depression, and stress) (r=0.167, 0.145, 0.167, P<0.001); sleep quality score was positively correlated with negative emotions (anxiety, depression, and stress) (r=0.512, 0.447, 0.513, P<0.001). The results of path analysis showed that the negative emotions (anxiety, depression, and stress) partially mediated between self-perceived noise intensity and sleep quality (β=0.123,P<0.001). Self-perceived noise intensity was positively correlated with negative emotions and sleep quality, and there was a path of self-perceived noise intensity → negative emotion → sleep quality (P<0.001), and the mediating effect accounted for 42.71%. Conclusion The positive rates of anxiety, depression, and stress are high among the noise-receiving workers in this manufacturing industry, and negative emotions characterized by anxiety, depression, and stress partially mediate the relationship between self-perceived noise intensity and sleep quality.
4.Repair of diabetic foot ulcer wound by anterolateral thigh chimeric perforator flap
Lingli JIANG ; Hai LI ; Zairong WEI ; Kewei ZENG ; Jian ZHOU ; Kaiyu NIE ; Shujun LI ; Chengliang DENG ; Wenhu JIN
Chinese Journal of Microsurgery 2021;44(2):141-145
Objective:To investigate the clinical effect of the anterolateral thigh perforator chimeric flap in the treatment of the wound of diabetic foot ulcer (DFU) .Methods:From January, 2018 to December, 2019, 14 cases wound of DFU of type II diabetic were treated by anterolateral thigh chimeric perforator flap. The patients were 10 males and 4 females, at 49 to 58 years old. Of the 14 patients, 10 with simple peripheral neuropathy, 4 with peripheral neuropathy complicated with vascular disease, and none with single vascular disease. With strict control of patients' blood glucose, antibiotics blended bone cement was applied or filled onto grade 2 or higher grade Wagner's DFU after debridement. In addition, the anterolateral thigh chimeric perforator flap was transferred 2 to 3 weeks later. The size of flap was 8 cm×3 cm-27 cm×7 cm. Regular followed-up were made after surgery.Results:Thirteen flaps survived in one stage after surgery. The other 1 flap had venous vascular crisis, and survived completely after active exploration. The patients were followed-up for 6-12 months. All the flaps survived well in good shape and texture. The donor and recipient areas healed well. The functional recoveries of the DF were satisfactory.Conclusion:Application of anterolateral thigh perforator chimeric flap in repair of the refractory wound of DF achieves a good clinical outcome and effectively improves the life quality of patients.
5.Long-term drainage following PTCD for treatment of ischemic-type biliary lesion after liver transplantation
Kewei ZHANG ; Yong CHEN ; Qingle ZENG ; Jianbo ZHAO ; Yanhao LI
Chinese Journal of Hepatobiliary Surgery 2010;16(9):648-651
Objective To evaluate the effectiveness, safety and clinical feasibility of long-term drainage following percutaneous transhepatic cholangiography and drainage (PTCD) for the treatment of ischemic-type biliary lesion (ITBL) after liver transplantation. Methods There were 11 patients with ITBL after liver transplantation. Of the 11 patients with a mean age of 42. 3, 10 were male and 1 female. All 11 cases were diagnosed by PTC or ERC (endocopic retiogiade cholangiogiaphy) before PTCD, and they responded poorly to medication or draining and stenting with ERCP. Long-term drainage following PTCD was performed, whereas adjuvant percutaneous aspiration through double guidewire technique was used for the patients with large quantities of chole mud. Results There were three types of ITBL: type Ⅰ (extrahepatic lesions, n=7), type Ⅱ (intrahepatic lesions, n= 1), and type Ⅲ (intra- and extra-hepatic alterations, n=3). PTCD was performed in all 11 patients successfully. The values of total bilirubin (TBIL) and direct reacting bilirubin (DBIL) were 206.70±54.18μmol/L, 170. 65±53. 97μmol/L and 90. 63± 13.00μmol/L, 63. 83± 13.61μmol/L before and 1 week after PTCD, respectively. The follow-up period was from 3 through 71 months (mean 20 months). During the follow-up, TBIL values ranged between 23.70 μmol/L and 241.0 μmol/L (mean 55.3±15.6 μmol/L), and DBIL values were between 8. 1 and 162.0 μmol/L (mean 32. 53±10. 21 μmol/L). Hepatic functions were good in 9 cases including 5 cases in which the drainage tube was withdrawn after long-time drainage (6~ 12 months, mean= 8.2 months) and 4 cases in which drainage continued. The other 2 cases received liver retransplantation for the grafts dyssynthesis of albumen after drainage for 3 and 8 months. Conclusion Long-term drainage following PTCD is an effective and safe approach for ITBL following liver transplantation.
6.Percutaneous intratumoral injection of lipiodol and chemotherapeutic agents emulsion for primary liver cancer
Yong CHEN ; Jianbo ZHAO ; Qingle ZENG ; Xiaofeng HE ; Wei LU ; Qiaohua ZHU ; Kewei ZHANG ; Dexiao HUANG ; Fan HE ; Junjie MAO ; Yanhao LI
Chinese Journal of General Surgery 2009;24(12):992-995
Objective To evaluate percutaneous intratumoral injection of chemotherapeutic agents lipiodol emulsion (CALE) for the treatment of primary liver cancer. Methods This study included 57 patients of hepatocellular carcinoma (n=49) and intrahepatic cholangiocarcinoma (n=8).53 were male and 4 were female,with a mean age of 48.02 years(range,19~70 years).In all,ninety CALE injections were assigned to 90 target areas within the lesions.Before the procedures,transcathetcr arterial chemoembolization (n=55) or infusion (n=2) was carried out in these patients.By arteriography,low blood supply of target areas was showed or it was concluded that superselective catheterization of supply arteries of lesions could not accomplished.Percutaneous intratumoral CALE injection was carried out under fluoroscopy or CT guidance.Therapeutic effect,side effect and complications were assessed based on clinical manifestation,laboratory examination and fluoroscopy or CT one week after procedure.Follow-up was carried out after 1,3,6 months and 1 year,and once every six months thereafter.Local recurrences were treated according to patients'will.Results 90 sessions of percutaneous injection were successfully performed on 57 patients,with 100% technique success rate.The volume of CALE iniected per session ranged 3.0-7.0 ml(mean,6.0 ml) in target size less than 3 cm,12.0-20 ml(mean,15 ml)in target size of 3-5 cm and 24-40 ml in target larger than 5 cm.Serum AFP was positive in 43 patients and decreased to normal in 14 patients(28%).54 lesions(60%)were with well distribution of the lipiodol-chemotherapy mixture on CT 1 month after procedure.Follow-up ranged from 2 months to six years(mean,16 months).The median survival time was 400 d.The cumulative survival rates at 200 d,600d was 85%and 30%,respectively.Complications included fever (n=22,24.4%),nausea and vomit(n=11,12.2%),and pain at the puncture site (n=17,18.9%).Conclusions Percutaneous intratumor CALE injection is safe and effective for the treatment of primary liver cancer.
7.Intra-arterial embolization with pingyangmycin-lipiodol emulsion for the treatment of hepatic cavernous hemangioma: an analysis of factors affecting therapeutic results
Qingle ZENG ; Yong CHEN ; Jianbo ZHAO ; Kewei ZHANG ; Yanhao LI
Journal of Interventional Radiology 2009;18(9):656-660
Objective To analyze the factors that might affect the therapeutic results of pingyangmycin-lipiodol emulsion intra-arterial sclerosing embolization (PLE-IASE) in treating symptomatic cavernous hemangioma of liver (SCHL). Methods PLE-IASE was performed in 89 patients with SCHL (32 males and 57 females). Before treatment the mean diameter of the hemangioma was (8.3±3.8) cm. Of 89 patients, 53 experienced anxiety, 35 suffered from right upper abdominal pain and the remaining one developed Kasabach-Merrit syndrome. Before PLE-IASE, the arteriographic classification was conducted based on hepatic arteriographic findings. Then pingyangmycin-lipiodol emulsion (PLE) was injected through the feeding artery. The dosage of pingyangmycin (PYM) was (9.8±4.4) mg and the dosage of lipiodol (LP) was (5.9±2.9) ml. The lipiodol deposition status was judged by the follow-up spot film taken immediately after PLE-IASE. The observations of the occurrence of complications, the relief of symptoms and the minification of SCHL were followed for 6-72 months after PLE-IASE. The linear regression analysis statistics was conducted by taking the minification as dependent variable and taking the arteriographic classification, lipiodol deposition status, the dosage of PYM, the dosage of lipiodol and the preoperative SCHL diameter as independent variable. Results Of all 89 cases of SCHL, hypervascular type was seen in 51, hypovascular type in 26 and arteriovenous shunt (AVS) type in 12. Good lipiodol deposition status was found in 64 patients and poor deposition in 25 patients after PLE-IASE. After PLE-IASE, the symptom of anxiety in 53 patients was relieved and the right upper abdominal pain was reduced in 33 cases although intermittent pain still remained in 2 patients. The blood platelet count of the patient with Kasabach-Merrit syndrome returned to normal after the treatment. The symptomatic relieve rate was 98.7%. No serious complications occurred in the follow-up period. The linear regression analysis showed that arteriographic classification, lipiodol deposition status and PYM dosage used in treatment had statistically significant impact on tumor minification, while the preoperative diameter of SCHL and lipiodol dosage used in treatment had no statistically significant impact on it. Conclusion PLE-IASE is an effective and safe interventional treatment for SCHL. Arteriographic classification, lipiodol deposition status and PYM dosage used in treatment have a significant correlation with the minification of SCHL, while the preoperative diameter of SCHL and lipiodol dosage used in treatment bear no relationship to the minification of SCHL.
8.Mini-endoscopes sympathectomy for hyperhidrosis palmaris
Yanmin LIU ; Ping WANG ; Kewei ZENG ; Beiwang SUN ; Bin OUYANG ; Xinqia ZHANG
Chinese Journal of Postgraduates of Medicine 2006;0(08):-
Objective To explore the feasibility of sympathectomy for hyperhidrosis palmaris using mini-endoscopic instruments and two ports approaches.Methods Thirty-one patients underwent sympathectomy using 3 or 5 mm mini-endoscopic through the cannula introduced at the fourth intercostal space and a 2.5 mm Hook-electrode through the cannula introduced at the second intercostal space on the anterior axillary line,without pleural drainage.Results All cases were successful without major intraoperative incident and postoperative complications,such as wound infection and bleeding.No analgesic was used.The average time of operations was(25?8) minutes each side.Hyperhidrosis palmaris was disappeared in 29 cases(93.5%),reduced in 2 cases(6.5%) postoperatively.Conclusions Sympathectomy using mini-endoscopic instruments and two ports approaches is safe,feasible and effective with good cosmetic result.
9.Percutaneous hepatocholangiostomy in treatment of recurrence hepatobiliary stones
Yanmin LIU ; Kewei ZENG ; Beiwang SUN ; Bin OUYANG ; Huiqing WEN ; Guangchun CHEN ; Ping WANG
Chinese Journal of Postgraduates of Medicine 2006;0(26):-
Objective To explore the potential predominance and value of percutaneous hepatocholangiostomy (PCH) in treatment of recurrence hepatobiliary stones (RHS). Methods Seventeen cases with RHS were treated by PCH from February 2001 to October 2005, which was an improved technology of percutaneous transhepatic cholangioscopy (PTCS) and made reference to the methods of percutaneous nephrostomy (PCN). Results Seventeen cases were successfully treated. The average blood loss was 40 ml (ranging from 15 to 100 ml), and stones were removed completely in 88.2% (15/17). The average hospital stay was 14 (ranging from 10 to 59) days. No one required postoperative analgesic. No postoperative bleeding and biliary leakage were found. Conclusions PCH has significant advantages of minimal invasion, little blood loss, less pain, less complications and quick recovery in the treatment of RHS.
10.Effect of HPV16 E6E7 oncogene on cell proliferation and cell cycle regulation of human colon cancer cell lines
Kewei JIANG ; Shan WANG ; Ruyu DU ; Yang KE ; Yingjiang YE ; Youzhi YU ; Weigang FANG ; Yi ZENG
Chinese Journal of General Surgery 1997;0(06):-
Objective To explore the mechanism of HPV infection in carcinogenesis and progression of colon cancer. Methods Human colon cancer cells, HCT116 (with wild-type p53) and SW480 (with mutant-type p53), were transfected by HPV16 E6E7 oncogenes using a recombinant adeno-associated virus vector system. The transfection efficiency was determined by flow cytometry. The expression of HPV16 E6 genes was determined by Western blot. The cell proliferation and cell cycle was studied by MTT method and flow cytometry. Results Western blot confirmed the expression of E6 gene in colon cells that were infected by rAAV-E6E7. The population doubling time of HCT116 cell, which was more than 48 hours at control group, decreased to 33 hours. HPV16 E6E7 increased cell percentage of S phase and decreased cell percentage of G0/G1. The population doubling time of SW480 cell was 77.06% decreased and the OD540 was 47.18% increased with interference of HPV16 E6E7 gene. Conclusion HPV16 E6E7 oncogene precipitates the proliferation and positively controls cell cycle of HCT116 and SW480 human colon cancer cells. HPV infection may closely relate to the carcinogenesis and progression of colon cancer.

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