1.Analysis of clinical and pathological characteristics of drug-induced live injury based on hepatotoxicity injury patterns
Honghai XU ; Shiwei ZHU ; Hui ZHANG ; Yufeng GAO ; Hua WANG
Chinese Journal of Clinical and Experimental Pathology 2024;40(2):172-178
Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58%).7 catego-ries of drugs induced DILI,with herbal ranking first(52%).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62%)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27%).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.
2.The value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening for non-small cell lung cancer: a meta-analysis
Honghai HE ; Huihui ZHANG ; Hua WU ; Hongli WANG ; Wei ZHAO ; Ping SUN ; Peng WANG
Chinese Journal of Health Management 2024;18(4):254-262
Objective:To evaluate the value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening of non-small cell lung cancer (NSCLC) based on meta-analysis.Methods:The original research literatures on the diagnostic value of CEA, CYFRA21-1 and CA125 in Chinese NSCLC patients were searched from databases of PubMed, Embase, The Cochrane Library, CNKI, VIP, Database and Wanfang database from establishment to June 2023. The literature screening, data extraction and quality evaluation were carried out independently by two researchers. The quality evaluation tool of diagnostic accuracy studies was used to evaluate the quality of the literature. A summary receiver operating characteristic (SROC) curve was used to assess the overall effectiveness of the tests. The outcome stability and publication bias were detected by using sensitivity analysis and Deeks′ test.Results:A total of 23 studies met the inclusion and exclusion criteria were included. The results of meta-analysis showed that the overall sensitivity of CEA, CYFRA21-1 and CA125 alone in the diagnosis of NSCLC was relatively low, it was 0.49(95% CI: 0.43-0.55), 0.56(95% CI: 0.49-0.63) and 0.41(95% CI: 0.33-0.49), respectively. The overall sensitivity of the combined detection of the three markers for the diagnosis of NSCLC increased to 0.83(95% CI: 0.69-0.91), but the overall specificity decreased to 0.76(95% CI: 0.69-0.83). Conclusions:The single detection of CEA, CYFRA21-1 and CA125 is not recommended for screening NSCLC in population receiving physical examination. Although the sensitivity of the combined detection of CEA, CYFRA21-1 and CA125 for screening NSCLC is improved, but the specificity is decreased, the misdiagnosis rate is increased, so the screening effect is limited.
3.Effect Evaluation of Responsible Segmental Decompression Combined with Orthopedic Fixation of Short-Segment Fusion Surgery for Treating Degenerative Lumbar Scoliosis
Hui ZENG ; Gangqiang WU ; Can HUANG ; Xiaojun HAN ; Bo LIU ; Cheng CHEN ; Long MA ; Bowen ZHANG ; Honghai WANG
Journal of Medical Biomechanics 2024;39(5):896-902
Objective To investigate the therapeutic effect of segmental decompression combined with corrective short-segment fusion surgery for the treatment of degenerative lumbar scoliosis.Methods In total,124 patients with degenerative lumbar scoliosis were selected and divided into short-and long-segment fusion groups using the random number table method,with 62 patients in each group.Posterior short-segment decompression,fixation,and fusion were performed in the short-segment fusion group;the fusion segment was the adjacent lumbar vertebra.Posterior long-segment decompression,fixation,and fusion were performed in the long-segment fusion group;the fusion segments included multiple adjacent lumbar vertebrae.At the 6th month after surgery,the coronal Cobb angle of lumbar convexity,sagittal Cobb angle of lumbar lordosis,intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,spinal canal diameter,Japanese Orthopedic Association(JOA)score,Oswestry Disability Index(ODI),degree of pain in the lower back and lower limbs,and postoperative complications were compared between the groups.Results The Cobb angle of the coronal lumbar scoliosis in the short-and long-segment fusion groups was significantly higher than that before surgery(P<0.05).At the 6th month after surgery,the intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,and spinal canal diameter in both groups increased,and those in the short-segment fusion group were higher than those in the long-segment fusion group(P<0.05);at the 6th month after the operation,the JOA scores of the short-segment and long-segment fusion groups were higher than those before surgery,and the JOA score of the short-segment fusion group was higher than that of the long-segment fusion group(P<0.05).The ODI score was lower than that before surgery in the short-and long-segment fusion groups,and the ODI score in the short-segment fusion group was lower than that in the long-segment fusion group(P<0.05).At the 6th month after surgery,the pain scores of the lower back and lower limbs in the short-and long-segment fusion groups were significantly higher than those before surgery(P<0.05).There were two cases of dural tears during decompression caused by lamina dura adhesion in the long-segment fusion group,and no serious complications were observed in the short-segment fusion group.Conclusions Both short-and long-segment decompression fixation fusion using a posterior approach can achieve good therapeutic effects for treating degenerative lumbar scoliosis.However,compared to the long-segment fusion group,the short-segment fusion group undergoing short-segment decompression fixation fusion through a posterior approach had a shorter surgical period,lower intraoperative blood loss,better recovery of lumbar function,and a lower risk of postoperative complications.
4.Research progress in animal models of liver regeneration based on the different injury modalities
Qian QIU ; Hui ZHANG ; Hehe YIN ; Honghai XU
Chinese Journal of Hepatobiliary Surgery 2024;30(7):552-556
The liver is a solid organ with excellent regenerative potential. Its regenerative ability is closely related to liver disease. In-depth study of the mechanism of liver regeneration is of great significance for understanding liver biology and developing regenerative medicine. The mouse has been the most widely used animal model of liver regeneration for its technical, economic and anatomical advantages. The current mouse models of liver regeneration include partial liver resection, chemical drug injury, and genetic engineering models. In this review, we compared their advantages, shortcomings and application prospects to provide reference for future research.
5.Interventional treatment of portal vein thrombosis via hepatic circular ligament approach during liver transplantation: a report of 3 cases
Chiyi CHEN ; Hao WANG ; Li ZHANG ; Qingjun GUO ; Honghai WANG ; Jisan SUN ; Guang CHEN ; Wentao JIANG
Chinese Journal of Organ Transplantation 2024;45(11):811-814
Three recipients with portal vein thrombosis experienced insufficient blood flow to transplanted liver due to residual thrombus after thrombectomy during liver transplantation. Alternative measures posed significant risks or technical challenges. To promptly restore blood flow, intraoperative intervention was performed via round ligament of donor liver for managing residual portal vein thrombus. Balloon dilation and vascular stenting effectively relieved local stenosis. After intervention, portal vein flow rate and volume fulfilled the standards and function of transplanted liver recovered smoothly. Follow-ups revealed unobstructed stents and no new thrombus formation. This simple, safe and efficacious technique has not been previously reported in the literature.
6.Erratum: Author correction to 'Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA' Acta Pharmaceutica Sinica B 13 (2023) 2585-2600.
Wenxin ZHANG ; Xiaohui PAN ; Yanjun XU ; Hongjie GUO ; Mingming ZHENG ; Xi CHEN ; Honghai WU ; Fengming LUAN ; Qiaojun HE ; Ling DING ; Bo YANG
Acta Pharmaceutica Sinica B 2023;13(10):4337-4337
[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].
7.The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy.
Mingming ZHENG ; Wenxin ZHANG ; Xi CHEN ; Hongjie GUO ; Honghai WU ; Yanjun XU ; Qiaojun HE ; Ling DING ; Bo YANG
Acta Pharmaceutica Sinica B 2023;13(4):1488-1497
Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.
8.Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA.
Wenxin ZHANG ; Xiaohui PAN ; Yanjun XU ; Hongjie GUO ; Mingming ZHENG ; Xi CHEN ; Honghai WU ; Fengming LUAN ; Qiaojun HE ; Ling DING ; Bo YANG
Acta Pharmaceutica Sinica B 2023;13(6):2585-2600
Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.
9.Effects of PSIP1 gene silencing on migration and invasion of oral squamous cell carcinoma cells
Yu SHI ; Xi CHEN ; Mengqi XU ; Yingying ZHANG ; Honghai JI ; Yingying JIANG
Journal of International Oncology 2022;49(3):129-133
Objective:To investigate the expression of PC4 and SFRS1 interacting protein 1 (PSIP1) in oral squamous cell carcinoma cells and the effects of PSIP1 silencing on the migration and invasion of oral squamous cell carcinoma cells, and to preliminarily explore its mechanism.Methods:The PSIP1 gene of oral squamous cell carcinoma cell line HN30 was silenced by RNA interference technique. HN30 cells were divided into si-NC group (transfected with siRNA-NC) and si-PSIP1 group (transfected with siRNA-PSIP1). Quantitative real-time PCR was used to detect the expression of PSIP1 mRNA. Scratch test and Transwell invasion test were used to detect the migration and invasion abilities of HN30 cells, and Western blotting was used to detect the expression levels of epithelial-mesenchymal transformation (EMT) related proteins in HN30 cells of the two groups.Results:The relative expression levels of PSIP1 of HN30 cells in the si-NC group and si-PSIP1 group were 1.00±0.00 and 0.21±0.06 respectively, with a statistically significant difference ( t=22.30, P=0.002). The scratch healing rates of the si-NC group and si-PSIP1 were (48.21±4.66)% and (42.05±11.74)% at 12 h respectively, with no statistically significant difference ( t=1.46, P=0.173), and the scratch healing rates of the two groups were (86.61±6.06)% and (67.76±3.62)% at 24 h respectively, with a statistically significant difference ( t=8.01, P<0.001). The invasion numbers of HN30 cells in the si-NC group and si-PSIP1 group were 91.00±7.05 and 23.34±4.98, and there was a statistically significantly difference ( t=19.20, P<0.001). Compared with the si-NC group, the migration and invasion abilities of HN30 cells in the si-PSIP1 group decreased significantly (all P<0.001). The expression levels of E-cadherin of the si-NC group and si-PSIP1 group were 1.06±0.02 and 1.43±0.13 respectively, with a statistically significant difference ( t=-4.94, P=0.036), and the expression levels of N-cadherin were 1.00±0.04 and 0.57±0.14 respectively, with a statistically significant difference ( t=5.03, P=0.007). Compared with the si-NC group, the expression level of E-cadherin in the si-PSIP1 group increased, while the expression level of N-cadherin decreased. Conclusion:Silencing the expression of PSIP1 can significantly inhibit the migration and invasion of HN30 cells, and the mechanism may be related to the effect of PSIP1 on the EMT pathway of oral squamous cell carcinoma.
10.Influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junction treated by neoadjuvant chemoradio-therapy combined with surgical resection: a prospective study
Peigang YANG ; Yuan TIAN ; Honghai GUO ; Bibo TAN ; Ping′an DING ; Yang LIU ; Zhidong ZHANG ; Yong LI ; Qun ZHAO
Chinese Journal of Digestive Surgery 2022;21(3):385-390
Objective:To investigate the influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junc-tion (AEG) treated by neoadjuvant chemoradiotherapy (nCRT) combined with surgical resection.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 120 AEG patients who were treated by nCRT combined with surgical resection in the Fourth Hospital of Hebei Medical University from March 2020 to March 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before nCRT were allocated into the experiment group, and patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before surgical resection were allocated into the control group. All patients received the same plan of nCRT combined with D 2 radical gastrectomy. Observation indicators: (1) grouping situations of the enrolled patients; (2) surgical and postoperative pathological situations; (3) postoperative complications and treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement date with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 120 patients were selected for eligibility. There were 85 males and 35 females, aged (60±9)years. There were 60 patients in the experiment group and 60 patients in the control group, respectively. (2) Surgical and postoperative pathological situations. Patients in the two groups underwent D 2 radical gastrectomy successfully, with R 0 resection. The number of lymph nodes harvest, the number of lymph nodes stained, the number of metastatic lymph nodes stained, the number of micro lymph nodes, the number of inferior mediastinal lymph nodes, the number of inferior mediastinal lymph nodes stained, cases in postoperative pathological stage N0, stage N1, stage N2, stage N3a were 40.6±13.9,20.1±7.7, 1.0(0,3.0), 8.1±2.8, 3.7±1.3, 2.0(1.0,2.0), 18, 13, 23, 6 in patients of the experiment group, respectively. The above indicators were 30.4±8.3, 12.7±3.5, 0(0,1.0), 6.2±2.0, 2.4±1.2, 1.0(0,1.0), 23, 21, 15, 1 in patients of the control group, respectively. There were significant differences in the above indicators between the two groups ( t=-5.01, 6.85, Z=-3.78, t=-4.04, -5.57, Z=-5.48, -2.12, P<0.05). (3) Postoperative complications and treatment. There were 5 cases of the experiment group and 7 cases of the control group with postoperative complications, showing no significant difference between the two groups ( χ2=0.37, P>0.05). The patients with postoperative complications were improved after symptomatic treatment. Conclusion:Compared with injection of carbon nanoparticle tracer 24 hours before surgical resection, injection of carbon nanoparticle tracer 24 hours before nCRT can improve the acquisition of lymph nodes in AEG treated by nCRT combined with surgical resection.

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