N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.

Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Objective To investigate the effect and mechanism of emodin on focal cerebral ischemia in rats based on myeloid differentiation factor 88(MyD88)/extracellular signal-regulated kinase(ERK)pathway and nuclear factor-κB(NF-κB)nuclear translocation.Methods SD rats were randomly divided into sham operation group,model group and emodin group,with six rats in each group.The rat model of transient middle cerebral artery occlusion(tMCAO)was established by middle cerebral artery embolization.Rats in the emodin group were given 40 mg·kg-1 emodin by gavage for three times at 72,48 and 24 hours before modeling.At 24 hours after modeling,the neurological function of rats was scored.TTC staining was used to detect the area of cerebral infarction.HE staining was used to observe the morphological changes of brain tissue.The mRNA expression levels of MyD88 and tumor necrosis factor-α(TNF-α)in brain tissue were detected by RT-qPCR.The expression levels of MyD88,ERK,p-ERK and TNF-α in brain tissue were detected by Western Blot.The protein expression of NF-κB in brain tissue was detected by immunofluorescence.Results Compared with the sham operation group,the neurological function score of the model group was significantly increased(P＜0.01),and the cerebral infarction area was significantly increased(P＜0.01).In the cortical area of the ischemic penumbra,cell necrosis,abnormal cell morphology,nuclear fragmentation and atrophy,and the number of cells decreased significantly;the mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly increased(P＜0.01,P＜0.001),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the proportion of NF-κB into nuclear cells was significantly increased(P＜0.001).Compared with the model group,the neurological function score of rats in the emodin group was significantly decreased(P＜0.05),and the area of cerebral infarction was significantly reduced(P＜0.05).The number and morphology of neurons in the ischemic penumbra cortex were restored to a certain extent.The mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly decreased(P＜0.05,P＜0.01),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly decreased(P＜0.05),and the proportion of NF-κB into nuclear cells was significantly decreased(P＜0.001).Conclusion Emodin has a preventive and protective effect on rats with focal cerebral ischemia,which may be related to its inhibition of MyD88 activation,ERK phosphorylation and NF-κB nuclear translocation,and then down-regulation of inflammatory cascades and secretion of pro-inflammatory factors such as TNF-α,thereby exerting anti-inflammatory effects.

The transmission and interaction of neural information between the hippocampus and the prefrontal cortex play an important role in learning and memory. However, the specific effects of learning memory-related tasks on the connectivity characteristics between these two brain regions remain inadequately understood. This study employed in vivo microelectrode recording to obtain local field potentials (LFPs) from the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) in eight rats during the performance of a T-maze task, assessed both before and after task learning. Additionally, dynamic causal modeling (DCM) was utilized to analyze alterations in causal connectivity between the vHPC and the mPFC during memory task execution pre- and post-learning. Results indicated the presence of forward connections from vHPC to mPFC and backward connections from mPFC to vHPC during the T-maze task. Moreover, the forward connection between these brain regions was slightly enhanced after task learning, whereas the backward connection was diminished. These changes in connectivity corresponded with the observed trends when the rats correctly performed the T-maze task. In conclusion, this study may facilitate future investigations into the underlying mechanisms of learning and memory from the perspective of connectivity characteristics between distinct brain regions.
Animals ; Hippocampus/physiology* ; Rats ; Prefrontal Cortex/physiology* ; Memory/physiology* ; Maze Learning/physiology* ; Learning/physiology* ; Male

Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.

Objective:This study aimed to investigate the viability and safety of a novel defecator in managing rectal fecal impaction.Methods:In a descriptive case series, this new defecator was administered to constipated individuals among the ages of 18 and 80 years who met the diagnostic criteria for rectal fecal impaction and were identified with acute rectal fecal impaction through CT scans. The contraindications for this defecator included: (1) Anal stenosis, acute intestinal obstruction, and intestinal perforation; (2) Concomitant rectal malignant tumors; (3) Coagulation dysfunction, low platelet counts, gastrointestinal bleeding, or other bleeding risks; (4) Patients with severe underlying conditions affecting the heart, brain, lungs, or other systems; (5) Individuals with mental health disorders. Based on these criteria, clinical data from 42 patients with rectal fecal impaction who underwent treatment with the new defecator at Deyang People's Hospital between July 2020 and April 2023 were retrospectively analyzed.The defecator comprises three components: a head, a spiral rod, and a handle, constructed from disposable stainless steel wire. The treatment procedure involves the following steps: The patient assumes a flexed, supine position on their left side with their buttocks slightly protruding from the bed's edge. A transparent sealing bag is affixed to the buttocks, centered around the anus. With gloved hands inserted through the bag's entrance, a cotton ball soaked in liquid paraffin lubricates the anal canal and the head of the defecator's spiral rod. The defecator is then slowly rotated and inserted into the anus, with careful attention to any changes in resistance. Once the spiral rod is fully inserted, the patient is instructed to inhale and defecate while the defecator is slowly withdrawn, carrying the dislodged fecal matter, and depositing it into the sealed bag. This operation is repeated 2 to 3 times, followed by the injection of either 100 ml of 36°C normal saline or 60 ml of liquid paraffin into the rectum. After a 5 to 8-minute wait, the patient assumes a squatting position to expel any remaining feces from the rectum. The study assessed the operation time, single treatment success rate, pain levels during treatment, and the occurrence of complications.Results:All 42 patients successfully underwent treatment with the new defecator device, achieving a single treatment success rate of 100%. The average operation time was 11.0 minutes (range: 9.0 to 13.3 minutes). During treatment, 20 cases (47.6%) reported moderate to severe anal pain, with 1 case (2.4%) experiencing anal fissure bleeding, and 6 cases (14.3%) reporting discomfort such as palpitations and sweating. No serious complications, including rectal perforation, were observed in any case.Conclusion:The new defecator device demonstrates ease of use and safety, making it a feasible option for treating acute rectal fecal impaction.

Objective:This study aimed to investigate the viability and safety of a novel defecator in managing rectal fecal impaction.Methods:In a descriptive case series, this new defecator was administered to constipated individuals among the ages of 18 and 80 years who met the diagnostic criteria for rectal fecal impaction and were identified with acute rectal fecal impaction through CT scans. The contraindications for this defecator included: (1) Anal stenosis, acute intestinal obstruction, and intestinal perforation; (2) Concomitant rectal malignant tumors; (3) Coagulation dysfunction, low platelet counts, gastrointestinal bleeding, or other bleeding risks; (4) Patients with severe underlying conditions affecting the heart, brain, lungs, or other systems; (5) Individuals with mental health disorders. Based on these criteria, clinical data from 42 patients with rectal fecal impaction who underwent treatment with the new defecator at Deyang People's Hospital between July 2020 and April 2023 were retrospectively analyzed.The defecator comprises three components: a head, a spiral rod, and a handle, constructed from disposable stainless steel wire. The treatment procedure involves the following steps: The patient assumes a flexed, supine position on their left side with their buttocks slightly protruding from the bed's edge. A transparent sealing bag is affixed to the buttocks, centered around the anus. With gloved hands inserted through the bag's entrance, a cotton ball soaked in liquid paraffin lubricates the anal canal and the head of the defecator's spiral rod. The defecator is then slowly rotated and inserted into the anus, with careful attention to any changes in resistance. Once the spiral rod is fully inserted, the patient is instructed to inhale and defecate while the defecator is slowly withdrawn, carrying the dislodged fecal matter, and depositing it into the sealed bag. This operation is repeated 2 to 3 times, followed by the injection of either 100 ml of 36°C normal saline or 60 ml of liquid paraffin into the rectum. After a 5 to 8-minute wait, the patient assumes a squatting position to expel any remaining feces from the rectum. The study assessed the operation time, single treatment success rate, pain levels during treatment, and the occurrence of complications.Results:All 42 patients successfully underwent treatment with the new defecator device, achieving a single treatment success rate of 100%. The average operation time was 11.0 minutes (range: 9.0 to 13.3 minutes). During treatment, 20 cases (47.6%) reported moderate to severe anal pain, with 1 case (2.4%) experiencing anal fissure bleeding, and 6 cases (14.3%) reporting discomfort such as palpitations and sweating. No serious complications, including rectal perforation, were observed in any case.Conclusion:The new defecator device demonstrates ease of use and safety, making it a feasible option for treating acute rectal fecal impaction.