1.Effect and mechanism of Biejiajian Pill on subcutaneous xenograft tumor model of hepatocellular carcinoma Huh7 cells
Lu LU ; Huanling CHEN ; Jian XU ; Yuanqin DU ; Xiaoli LIU ; Yingsheng WU ; Chengting WU ; Wei BAN ; Jingjing HUANG ; Hongna HUANG
Journal of Clinical Hepatology 2026;42(1):125-133
ObjectiveTo investigate the inhibitory effect of Biejiajian Pills (BJJW) on the growth of liver cancer, as well as its potential mechanism in mediating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group, BJJW group (2.2 g/kg), and metformin group (250 mg/kg), and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment; HE staining was used to observe histopathological changes; the levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in tumor tissue were measured; immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Tukey’s test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group, the BJJW group had a tumor inhibition rate of 45.73%, with significant reductions in both tumor volume and weight (P<0.01). Pathological examination showed that compared with the model group, the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group, the BJJW group had a significant increase in ROS level (P<0.001) and a significant reduction in ATP level (P<0.001), as well as significant increases in p-AMPK/AMPK ratio (0.81±0.20 vs 0.13±0.04, P<0.01) and p-ULK1/ULK1 ratio (0.69±0.17 vs 0.18±0.13, P<0.01) and a significant reduction in p-mTOR/mTOR ratio (1.34±0.16 vs 3.20±0.62, P<0.01). ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction, increasing the level of ROS, reducing the level of ATP, and activating the AMPK/mTOR signaling pathway.
2.Protective effects of Wuling capsule on concanavalin A-induced autoimmune hepatitis mice
Lin CHEN ; Fan CAO ; Zhongxing SONG ; Xin KONG ; Zhishu TANG ; Hongna LIU ; Jianping ZHOU ; Zhaojun CAO
Academic Journal of Naval Medical University 2025;46(1):65-71
Objective To investigate the protective effects of Wuling capsule on mice with autoimmune hepatitis(AIH).Methods Mice were randomly divided into control group,AIH model group,Wuling capsule low-dose group(0.5 g·kg-1·d-1),Wuling capsule middle-dose group(1.0 g·kg-1·d-1),and Wuling capsule high-dose group(2.0 g·kg-1·d-1),with 10 mice in each group.The Wuling capsule groups were administered with Wuling capsule suspension of different doses orally at a volume of 10 mL/kg once daily;the control group and AIH model group were given the same volume of saline by gavage.After 14 d of administration,mice in the AIH model group and Wuling capsule groups were injected with concanavalin A(20 mg/kg)via the tail vein,and the serum,liver,and spleen were collected 8 h after injection.Serum alanine transaminase(ALT)and aspartate transaminase(AST)levels were measured using an automatic biochemical analyzer;hematoxylin-eosin staining was used to observe the pathological structure of the liver tissue;the contents of interleukin(IL)-6,IL-4,and tumor necrosis factor(TNF)-α in liver were determined by enzyme-linked immunosorbent assay,and quantitative polymerase chain reaction was used to determine the relative mRNA expression levels of IL-6,IL-4,TNF-α,Toll-like receptor 4(TLR4),and nuclear factor κB(NF-κB)in the liver.Fluorescence immunoassay was used to analyze the expression and nuclear translocation of NF-κB p65 protein in the liver.Results Compared with the control group,the AIH model group showed abnormal liver morphology and structure,increased serum ALT and AST levels,increased contents of IL-4,IL-6,and TNF-α in the liver,upregulated mRNA expression levels of IL-6,IL-4,TNF-α,TLR4,and NF-κB in the liver,and increased nuclear entry of NF-κB p65.Wuling capsule significantly improved the pathological structure of the liver in AIH mice,reduced serum ALT and AST levels,decreased the contents of IL-4,IL-6,and TNF-α in the liver and the mRNA expression levels of TLR4,NF-κB,IL-4,IL-6,and inhibited the nuclear activation of NF-κB p65.Conclusion Wuling capsule has significant protective effects on AIH mice,which may be related to the TLR4/NF-κB signaling pathway.
3.Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma
Xiaoli LIU ; Qinwen TAN ; Jian XU ; Huanling CHEN ; Jie YU ; Lu LU ; Mingkan DAI ; Jingjing HUANG ; Hongna HUANG ; Dewen MAO
Journal of Clinical Hepatology 2024;40(12):2531-2537
Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells, and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma, amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention, showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy, its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice, in order to provide new ideas for immunotherapy for liver cancer.
4.Clinical Research Progress in Acupuncture for the Treatment of Tourette Syndrome
Mingyuan HAN ; Xiaolin LYU ; Zhongren SUN ; Shaopeng LIU ; Xinyuan CAO ; Yuxin WANG ; Ying FAN ; Xiangxin ZENG ; Hongna YIN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):181-185
Tourette syndrome(TS)is a chronic neurodevelopmental disorder.Acupuncture can effectively improve the clinical symptoms of TS patients.This article systematically summarized the clinical research status of acupuncture for the treatment of TS in recent years from the aspects of characteristic acupuncture methods,characteristic needles and comprehensive therapies,and put forward suggestions and prospects for systematically elaborating the peripheral-central mechanism of acupuncture for TS around the intestinal immunity and brain network mechanism in the future,so as to provide reference for optimizing clinical research and treatment.
5.Effect and safety of preoperative short-course radiotherapy combined with neoadjuvant chemotherapy for elderly patients with locally advanced rectal cancer
Liangxue HOU ; Hongna WANG ; Yuanquan LU ; Junqi LIU
Chinese Journal of Geriatrics 2024;43(3):317-323
Objective:To assess the impact of preoperative short-course radiotherapy combined with neoadjuvant chemotherapy on elderly patients with locally advanced rectal cancer after a 2-year follow-up.Methods:In this retrospective cohort study, we included 446 consecutive cases of elderly patients diagnosed and treated for locally advanced rectal cancer(stage Ⅱ-Ⅲ with T3-T4 and/or positive regional lymph nodes)at the First People's Hospital of Shangqiu city from January 2012 to December 2019.The patients were divided into two groups based on the treatment method: an observation group(107 cases)and a control group(339 cases).The patients in the observation group underwent preoperative short-course radiotherapy combined with neoadjuvant chemotherapy.The regimen included short-term radiotherapy(25 Gy over 1 week in 5 fractions)followed by 4 courses of chemotherapy(CAPOX regimen).On the other hand, the control group received concurrent radiotherapy and chemotherapy.The regimen involved 50 Gy over 5 weeks in 25 fractions and concurrent capecitabine chemotherapy.Afterward, total rectal mesentery resection was performed, and postoperatively, 2 and 6 courses of CAPOX chemotherapy were continued.Follow-up was conducted until 31 December 2021, with the primary observation being the disease-free survival(DFS)of patients in both groups.Secondary observations included overall survival(OS)time, lesion progression-free survival(PFS)time, local recurrence rate, and the rate of acute toxicity events.Cox regression analyses were conducted to compare the factors influencing DFS.Results:Among the 446 patients, 303(67.9%)were male and 143(32.1%)were female.The patients in the observation group were found to be younger and had a higher proportion of Eastern Collaborative Oncology Group(ECOG)physical status score 0 compared to the control group(both P<0.05).Additionally, the two groups differed significantly in terms of MRI T stage, N stage, distance from the external anal verge, rectal mesorectal fascial infiltration, pathological stage, and chemotherapy-to-surgery time interval(all P<0.05).Throughout a mean follow-up period of(20.7±3.5)months, there were 76 deaths, 89 distant metastases, and 32 local recurrences.The results of Kaplan-Meier survival analysis revealed that the observation group had a higher disease-free survival(DFS)rate at 2 years of follow-up compared to the control group[73.8%(79/107) vs.68.1%(231/339), Log-rank χ2=2.676, P=0.041].Additionally, the median DFS time was longer in the observation group[19(12, 22)months]compared to the control group[16(11, 19)months]( Z=2.774, P=0.038).Furthermore, the observation group exhibited a significantly longer OS time[26(21, 33)months]compared to the control group[22(18, 14)months]( Z=2.879, P=0.032).However, the median PFS time was similar in both groups[20(14, 25)months vs.16(12, 21)months]( Z=1.545, P=0.123).The incidence of distant metastasis was 18.7%(20/107)in the observation group and 20.4%(69/339)in the control group(Log-rank χ2=0.341, P=0.708), indicating no significant difference.Similarly, there was no significant difference in the risk of local recurrence between the observation group[9.3%(10/107)]and the control group[6.5%(22/339)](Log-rank χ2=0.996, P=0.318).In terms of adverse reactions, there was no statistically significant difference in the incidence of grade≥3 acute toxic reactions between the two groups[19.6%(21/107) vs.12.1%(41/339), Log-rank χ2=1.661, P=0.148].A multifactorial Cox regression analysis revealed that age( HR=0.586, P=0.005), ECOG score( HR=0.721, P=0.028), MRI T-stage( HR=0.605, P=0.008), rectal mesenteric fascial infiltration( HR=1.649, P=0.012), and distance from the external anal verge( HR=0.638, P=0.041)were associated with DFS. Conclusions:The findings indicate that the combination of preoperative short-course radiotherapy and neoadjuvant chemotherapy in elderly patients with locally advanced rectal cancer demonstrates favorable short-term effectiveness and safety.This approach shows promise in improving outcomes for elderly patients with locally advanced rectal cancer.
6.Safety and effectiveness of single-channel endoscope multibending-assisted endoscopic submucosal dissection for gastric lesions in difficult locations (with video)
Zeyu WU ; Lijuan MAO ; Ting ZHANG ; Tian JIN ; Xiaoyun LU ; Hongna LU ; Chang'en LIU ; Xiao HU ; Qide ZHANG
Chinese Journal of Digestive Endoscopy 2024;41(8):658-662
The gastric fundus fornix and upper part of the gastric body pose challenges for endoscopic submucosal dissection (ESD), resulting in unsatisfactory resection outcomes for lesions in these areas,because of the difficulty in the endoscope reaching the lesion site. Drawing inspiration from the formation of α loop during flexible colonoscopy and double-channel multibending gastroscope, a single-channel treatment gastroscope was utilized to create a multibending state (referred to as single-channel endoscope multibending method, SCMB). This method was employed to treat 6 patients with lesions in the stomach at Digestive Endoscopy Center of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2021 to December 2021. There were 3 cases in the gastric fundus fornix, 2 cases in the greater curvature on the upper part of the gastric body, and 1 case in the posterior wall of gastric fundus and subcardia. After 2-3 attempts during surgery, SCMB was successfully performed in all cases within 60-120 seconds. All 6 cases completed successful endoscopic resection within 20-80 minutes without significant complications, including 4 cases of ESD and 2 cases of endoscopic full-thickness resection (EFR). Preliminary results indicate that SCMB method during ESD and its derivative technologies are both safe and effective for lesions in challenging areas where gastric ESD is difficult to perform. During surgery, this approach facilitates the front end of endoscope access to the lesion, providing a clear visual field and a stable dissection plane.
7.GAO Weibin's experience in treatment of cerebral infarction in the recovery period with "brain electric field" therapy.
Kexing NING ; Shaopeng LIU ; Lijun LIN ; Yang CUI ; Xuefeng JIAO ; Fei HUANG ; Zhongren SUN ; Hongna YIN
Chinese Acupuncture & Moxibustion 2024;44(11):1299-1303
The "brain electric field" therapy is a novel electroacupuncture method created by Professor GAO Weibin to treat cerebral infarction in the recovery period. This therapy is suitable for the treatment of motor disorders, sensory disorders, cognitive disorders, hemianopsia and bulbar paralysis during the recovery period of cerebral infarction. Based on the different symptoms, the corresponding brain functional areas are selected, supplemented with Taiyang 2, Tunyan 2, Tiyan, Gongxue and Xiatianzhu. These points are attached to electric acupuncture apparatus, and stimulated with dense wave, at frequency of 50 Hz and tolerable intensity. This therapy presents a remarkable effect on cerebral infarction in the recovery period, providing the new approach to the treatment of this disease.
Humans
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Cerebral Infarction/therapy*
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Electroacupuncture
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Acupuncture Points
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Brain/physiopathology*
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Male
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Middle Aged
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Female
8.Monitoring of intra-abdominal pressure:a survey of ICU nurses'practice and cognition in 31 hospitals in Shandong Province
Beibei LIU ; Yuanyuan LI ; Jicheng ZHANG ; Hongna YANG ; Fengzhi CHEN ; Xue BAI
Chinese Journal of Nursing 2023;58(21):2610-2616
Objective To understand the current situation of practice and cognition of ICU nurses on intra-abdominal pressure monitoring in tertiary general hospitals in Shandong Province,and to analyze the factors affecting their cognition,so as to provide references for formulating intra-abdominal pressure monitoring standards and procedures,and carrying out targeted training in the future.Methods A convenience sampling method was used,and a self-designed questionnaire on practice and cognition of intra-abdominal pressure monitoring was used to survey ICU nurses from tertiary general hospitals in 16 prefecture-level cities in Shandong Province from September to November 2022.Results A total of 627 valid questionnaires were collected,involving 31 tertiary general hospitals(24 tertiary A hospitals,77.42%;7 tertiary B hospitals,22.58%).The operation rate of intra-abdominal pressure monitoring was low(73.37%),and the main reasons were that they had not received intra-abdominal pressure monitoring related training(61.08%),with only 111(24.94%)nurses choosing the intersection of the mid-axillary line and the iliac crest as the reference zero point measurement,274(61.57%)nurses not taking an reading at the end of expiration.The intra-abdominal pressure monitoring cognition score was 0~16(7.88±2.79)points,and only 5 questions had a correct answer rate of≥50%.Conclusion The standardization of intra-abdominal pressure monitoring practice by ICU nurses in tertiary general hospitals in Shandong Province needs to be strengthened,and their cognition needs further training.It is suggested to unify and implement the standards and procedures of intra-abdominal pressure monitoring,further accelerate the training of intra-abdominal pressure monitoring technology,and improve the standard execution rate and cognitive level of ICU nurses on intra-abdominal pressure monitoring.
9.Regulatory Mechanism of NCOA4-mediated Ferritinophagy and its Progress in Colitis and Colitis-associated Cancer
Dan ZHANG ; Qiqi HUANG ; Hongna LI ; Li LIU ; Huirong LIU ; Xiaopeng MA
Chinese Journal of Gastroenterology 2023;28(10):620-625
Abnormal iron metabolism mediated by ferritinophagy is one of the most important mechanisms in the occurrence of ferroptosis.The regulatory mechanism of ferritinophagy mainly involves the transcription of NCOA4 and its corresponding protein modifications.Ferroptosis plays an important role in the development of colitis and colitis-associated cancer,and target-oriented regulation of ferroptosis can alleviate colonic inflammatory response and induce the tumor cell death.This article mainly reviewed the regulatory mechanism of NCOA4-mediated ferritinophagy and its progress in colitis and colitis-related cancer,which may provide a new point for the investigation on mechanism of colitis and inflammation-cancer transformation.
10.Endoscopic and clinicopathological features of gastric adenocarcinoma of fundic gland type of chief cell predominant type
Hongna LU ; Tingsheng LING ; Xuesong ZHANG ; Guowei LIU ; Chunnian WANG ; Xi DENG ; Li ZHANG
Chinese Journal of Digestive Endoscopy 2023;40(11):900-908
Objective:To investigate the clinical, endoscopic and pathological features, and treatment and prognosis of gastric adenocarcinoma of fundic gland type of chief cell predominant type (GA-FG-CCP).Methods:Data of 40 GA-FG-CCP patients with 41 lesions diagnosed by histopathology at Ningbo Medical Center Lihuili Hospital and Shanghai East Hospital from January 2018 to May 2023 were collected. Their clinical and endoscopic features, pathological features, immunohistochemical results, endoscopic treatment, and prognosis were analyzed.Results:Among the 40 GA-FG-CCP patients, there were 15 males and 25 females, and the mean age was 60.03 years. Most of them had no obvious clinical symptoms or family history of tumor. Except one case, others had no helicobacter pylori infection. The endoscopic features of white light observation were: ① the main location was the upper part of the gastric body (63.41%, 26/41); ② faded or whitish mucosal surface (56.10%, 23/41); ③ dilated vessels with branch architecture (78.05%, 32/41); ④ no background mucosal atrophy (100.00%, 41/41). The features of magnifying endoscopy with narrow band imaging (ME-NBI) were: ① no obvious demarcation line (85.37%, 35/41); ② enlargement of the crypt opening (87.80%, 36/41); ③ widening of the intervening part (92.68%, 38/41); ④ lack of irregular microvascular pattern (95.12%, 39/41). All patients were confirmed gastric adenocarcinoma of the fundic gland by biopsy. The glands showed a low degree of dysplasia, similar to the differentiation of chief cell predominant pattern, also with scattered parietal cells, forming irregular and anastomosing cords. In the 40 patients, 20 did not receive endoscopic therapy. Twelve out of 21 lesions in 20 cases treated with endoscopic resection infiltrated into the submucosa (20-520 μm), 9 cases were intramucosal carcinoma. There was no lymphatic or venous infiltration, and horizontal and vertical margins were negative. Immunohistochemical staining results showed that the tumor was postive for pepsinogen-Ⅰ and MUC 6, with scattered postive for H +-K +-ATPase, but negative for MUC5AC, MUC2 and CD10, and the Ki-67 labeling index was low. No patients had recurrence or metastasis during mean follow-up of 15.85 months. Conclusion:GA-FG-CCP is rare and very well differentiated. Its clinical symptoms are not obvious, but there is endoscopic characteristics. The detection rate of GA-FG-CCP can be improved by white light and ME-NBI, and the diagnosis can be confirmed by pathology and immunohistochemical staining.

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