Herb-induced liver injury(HILI)tends to have complex toxic material basis and toxic mechanism,which greatly affects the safety of traditional Chinese medicine.This article summarizes the main toxic components of Chinese herbal medicine causing liver injury and their mechanism of action.The toxic components of Chinese herbal medicine causing liver injury can be classified into two categories of drug-derived and non-drug-derived toxic components.Drug-derived toxic components mainly include alkaloids,terpenoids,anthraquinones,and phenylpropanoids,and their mechanism of action involves oxidative stress,apoptosis and necrosis,CYP450 enzymes,and genotoxicity.Non-drug-derived toxic components mainly include pesticide residues,sulfur dioxide residues,heavy metals,fungi,and plant growth regulators,and their mechanisms involve oxidative stress,apoptosis,metabolic disorders,and CYP450 enzymes.On this basis,this article further proposes the unsolved problems and research difficulties,in order to promote the basic research on the hepatotoxicity of traditional Chinese medicine.

Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.

Hydrogen sulfide (H₂S) is a gas signaling molecule with versatile bioactivities; however, its exploitation for disease treatment appears challenging. This study describes the design and characterization of a novel type of H₂S donor-drug conjugate (DDC) based on the thio-ProTide scaffold, an evolution of the ProTide strategy successfully used in drug discovery. The new H₂S DDCs achieved hepatic co-delivery of H₂S and an anti-fibrotic drug candidate named hydronidone, which synergistically attenuated liver injury and resulted in more sufficient intracellular drug exposure. The potent hepatoprotective effects were also attributed to the H₂S-mediated multipronged intervention in lipid peroxidation both at the whole cellular and lysosomal levels. Lysosomal H₂S accumulation and H₂S DDC activation were facilitated by the hydrolysis through the specific lysosomal hydrolase, representing a distinct mechanism for lysosomal targeting independent of the classical basic moieties. These findings provided a novel pattern for the design of optimally therapeutic H₂S DDC and organelle-targeting functional molecules.

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.

Objective:To evaluate the necessity, safety and efficacy of endovascular treatment for cerebral infarction caused by middle cerebral artery (MCA) stenosis with hypoperfusion in the blood supply area of the lenticulostriate artery.Methods:The clinical and surgical data of patients with MCA atherosclerotic disease who underwent endovascular treatment in the First Affiliated Hospital of Zhengzhou University from January 2014 to October 2021 were retrospectively analyzed. A total of 6 patients with cerebral infarction caused by MCA stenosis with hypoperfusion in the blood supply area of the lenticulostriate artery were selected. The preoperative and postoperative clinical imaging characteristics, perioperative complications and follow-up of these 6 patients were summarized and evaluated.Results:After the endovascular treatment, the imaging of the lenticulostriate artery in all the 6 patients was clearer than that before the operation, and the number of main trunks of the lenticulostriate artery shown by imaging in 2 patients was more than that before operation. The computer tomography perfusion of 6 patients after the endovascular treatment showed that perfusion in the supply area of the lenticulostriate artery was significantly improved compared with pre-operation. No stroke, transient ischemic attack (TIA) and death occurred during the perioperative period. The time of clinical follow-up was 360 (322, 495) days, and there were no stroke, TIA or death occurring in the corresponding artery. All the 6 patients underwent imaging follow-up, of which 3 patients underwent digital subtraction angiography and 3 underwent CT angiography. The lumen of the target vessels showed patency in all patients.Conclusions:With rigorous imaging evaluation, endovascular treatment may be safe and effective for cerebral infarction caused by MCA stenosis with hypoperfusion in the blood supply area of the lenticulostriate artery.

Objective: To compare the clinical effects of endoscopic thyroidectomy using a modified gasless transsubclavian approach and the traditional neck approach for unilateral papillary thyroid carcinoma (cN0). Methods: The clinical data of 135 patients with cN0 papillary thyroid carcinoma who underwent unilateral thyroidectomy in the Department of Thyroid Surgery, the First Hospital of Jilin University from October 2020 to November 2022 were retrospectively analyzed. There were 37 males and 98 females, aging (43.2±8.8) years (range: 21 to 59 years). There were 51 cases using the modified gasless transsubclavian approach (TS group) and 84 cases using the traditional neck approach (TN group). Comparative analyses were performed between the operative results of the 2 groups by t-test, Wilcoxon rank sum test, and χ² test. Results: All endoscopic operations were successfully completed without conversion to the traditional neck approach. Compared to the TN group, the TS group had a longer operation time (M(IQR)) (73.5 (22.5) minutes vs. 90.0 (30.0) minutes, Z=-5.831, P<0.01), more postoperative drainage (60 (25) ml vs. 95 (45) ml, Z=-6.275, P<0.01), higher hospitalization costs (22 687 (3 488) yuan vs. 26 652 (2 431) yuan, Z=-6.944, P<0.01), and a higher rate of parathyroid autotransplantation (15.5% (13/84) vs. 60.8% (31/51), χ²=29.651, P<0.01). There was no significant difference in the total exposure rate of the central compartment, postoperative hospitalization time, the number of dissected lymph nodes, the number of metastatic lymph nodes, C-reactive protein ratio before and after operation, and preoperative and postoperative parathyroid hormone (all P>0.05). Conclusions: Endoscopic thyroidectomy using the modified gasless transsubclavian approach is safe for cN0 papillary thyroid carcinoma, with longer operating time, more postoperative drainage, higher hospitalization costs, and moredifficulty in preserving the inferior parathyroid gland in situ compared to traditional open surgery.

Objective:To observe the level of mindfulness and coping style in patients with acute cerebral infarction (ACI) after interventional therapy, and analyze the intermediary effect of benefit finding between them, so as to provide a theorectical basis of implement mindfulness intervention in clinical practice.Methods:The 130 patients with ACI after interventional treatment in the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2021 were included in this cross-sectional survey study. The general data questionnaire, Five-factor Mindfulness Scale (FFMQ), Benefit Finding Rating Scale (BFS), and Simple Coping Style Questionnaire (SCSQ) were used to analyze the relationship between benefit finding, mindfulness level and coping style, and the intermediary effect of benefit finding between them.Results:The total FFMQ score of 130 ACI patients after interventional therapy was (123.34 ± 5.14) points. The BFS score, positive coping score and negative coping score were (49.73 ± 3.41), (20.35 ± 2.25), (13.18 ± 1.45) points, respectively. The level of mindfulness and benefit were positively correlated with positive coping ( r=0.687, 0.737, both P<0.05). The level of mindfulness and benefit were negatively correlated with negative coping( r=-0.654, -0.779, both P<0.05). It was found that mindfulness level played a partial intermediatory effect on positive coping and negative coping in ACI patients after interventional therapy, with contribution rates of 49.71% and 64.58%, respectively. Conclusions:Benefit finding plays a partial intermediary effect on the level of mindfulness and coping style of patients with ACI after interventional therapy.

Objective:To investigate the risk factors related to successful endovascular recanalization for non-acute long segmental occlusion of internal carotid artery and propose a strategy for selecting proper candidates for such procedure.Methods:From January 2018 to October 2022, 120 consecutive patients with non-acute long segmental internal carotid artery occlusion received the first intended endovascular recanalization treatment in the First Affiliated Hospital of Zhengzhou University. Potential variables including epidemiology, symptomatology, angiographic morphology and interventional techniques were retrospectively analyzed. Univariate and multivariate logistic regression analyses were made to investigate the independent risk factors for successful recanalization. Four types were divided according to the existence of tapered stump and ophthalmic artery flow reversion based on DSA images: A: tapered stump (-), ophthalmic artery flow reversion (-); B: tapered stump (-), ophthalmic artery flow reversion (+); C: tapered stump (+), ophthalmic artery reversion (-); D: tapered stump (+), ophthalmic artery (+). Investigation of the relationship between procedure success rate and group dividing was performed.Results:Totally 120 patients were all included. The technical success rate was 75.83% (91/120). The periprocedural complication rate was 9.17% (11/120), including 4 (3.33%) intracranial hemorrhagic events, 1 (0.83%) ischemic stroke event, 1 (0.83%) microcatheter perforation, 3 (2.75%) cavernous carotid fistulas, 2 (1.67%) iatrogenic dissections. None of these complications led to severe neurological damage or death. Through multivariate logistic regression, tapered stump (OR=4.10, 95%CI 1.19-14.16), retrograde filling of ophthalmic artery (OR=3.16, 95%CI 1.13-8.88), only cervical segment occlusion of internal carotid artery (OR=10.78, 95%CI 2.08-55.74) were the independent risk factors associated with higher technical success rate. All cases were divided into A-D four types considering the tapered stump and reversed ophthalmic flow existing or not. Technical success rates in A-D types were 30.00% (3/10), 66.67% (8/12), 70.00% (28/40), 89.66% (52/58) respectively, and the complication rates of the four types were 10.00% (1/10), 8.33% (1/12), 17.50% (7/40), 3.45% (2/58). Multivariate logistic regression showed group pattern was the independent factor on technical success rate (OR=3.72, 95%CI 1.42-9.77).Conclusions:Tapered stump, reversed ophthalmic artery flow and pure extracranial artery occlusion are the independent factors for technical success rate. Group pattern which covered the tapered stump and reversed ophthalmic artery flow is also related to technical success rate. However, the results need further confirmation with the prospective trial and a larger sample.

Objective To investigate the predictive value of geriatric nutritional risk index(GNRI)for stroke-associated pneumonia in elderly patients with acute ischemic stroke(AIS).Methods A total of 1505 elderly patients with AIS admitted to Department of Neurology of the Second Affili-ated Hospital of Nanchang University from January 2017 to October 2022 were included in this retrospective study.According to GNRI nutritional assessment,they were divided into T1(high nutritional risk,GNRI＜82,n=49),T2(moderate nutritional risk,GNRI 82-91,n=305),T3(low nutritional risk,GNRI 92-98,n=555),and T4(no nutritional risk,GNRL＞98,n=596)groups.Additionally,based on the discharge diagnosis,they were further classified into pulmonary infection group(150 cases)and non-infection group(1355 cases).These subjects were also ran-domly assigned into training,validation,and testing sets in a ratio of 16∶4∶5.Multivariate logis-tic regression analysis was performed to identify the risk factors for pulmonary infection in stroke patients.Logistic regression and XGBoost algorithms were used to establish prediction models for pulmonary infection.The models were evaluated with their AUC value,accuracy,sensitivity,and specificity based on ROC curve analysis.Results Multivariate logistic regression analysis revealed that hypertension,invasive procedures,consciousness disorders,CRP,lymphocyte count,hemoglo-bin and GNRI were independent risk factors for pulmonary infection in stroke patients(P＜0.05).The AUC value of the GNRI model for predicting pulmonary infection in the testing set was 0.742(95％CI:0.651-0.833),with an accuracy of 71.8％,sensitivity of 76.7％,and specificity of 71.2％.The combined model of clinical indicators(hypertension,invasive procedures,conscious-ness disorders,CRP,lymphocyte count,hemoglobin)and GNRI achieved an AUC value of 0.776(95％CI:0.700-0.853),accuracy of 74.8％,sensitivity of 83.3％,and specificity of 73.8％in the test set.Conclusion GNRI is an independent risk factor for pulmonary infection in elderly pa-tients with AIS and has a certain value in predicting pulmonary infection after AIS.