In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

Objective: To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS). Methods: Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group, with 20 rats in each group. Rats in the modeling group were subjected to preparing experimental UC models by drinking 4％ DSS for seven consecutive days. Two modeled rats and two normal rats were randomly selected for model identification. After the success of UC model was confirmed, the remaining 18 modeled rats were randomly divided into three groups, a model group, a model + herbal cake-partitioned moxibustion group, and a model + mild moxibustion group, with six rats in each group; the remaining normal rats were randomly divided into three groups, a normal group, a normal + herbal cake-partitioned moxibustion group, and a normal + mild moxibustion group, with six rats in each group. After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion, hematoxylin-eosin (HE) staining technique was used to observe the pathological changes of colon tissue under a light microscope; Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin, Claudin, junction adhesion molecular 1 (JAM1), mucin 2 (MUC2), and transforming growth factor beta1 (TGF-β1) in rat colon tissue. Results: Compared with the normal group, the colon tissue was severely damaged, the pathological score was significantly increased, and the protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 were significantly decreased in the model group (P<0.01); while there were no significant differences in the colonic histopathological score, protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 in the normal + herbal cake-partitioned moxibustion group and the normal + mild moxibustion group (P>0.05). Compared with the model group, the model + herbal cake-partitioned moxibustion group and the model + mild moxibustion group showed repaired colon tissue, ulcer healing, significantly reduced pathological score, and significantly increased protein expression levels of JAM1, MUC2, and TGF-β1 (P<0.05); the Occludin protein expression level in the colon tissue of the model + mild moxibustion group was increased (P<0.01). Conclusion: Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats; both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1, MUC2, and TGF-β1 in the colon tissue of UC rats. Mild moxibustion can up-regulate Occludin protein expression. This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.

Objective To investigate the effects of combined general and epidural anesthesia on intestinal barrier function in patients with obstructive jaundice after surgery.Methods Forty patients with obstructive jaundice,male 1 5 cases,female 25 cases,aged 26-65 years,of ASA Ⅰ-Ⅲ,with TBIL >100 μmol/L were randomly divided into two groups (n =20):the general intravenous anes-thesia group (group GA)and the combined general and epidural anesthesia group (group GE).Pa-tients of group GA with oxygen mask rapid intubate induction of endotracheal after general anesthesia. Patients of group GE take left side line of T8~9 or T9 ~1 0 segmental epidural puncture and insert cathe-ter,after changing the hypothesis to be 2% lidocaine 5 ml for test quantity,confirm without anesthe-sia complications and other abnormalities after general anesthesia 5 minutes later.Peripheral venous blood was sampled when entering the operating room (T1 ),and at the end of operation (T2 ),24 hours after operation(T3 )and 48 hours after operation (T4 ).The concentration of D-lactate (D-LA) was measured using ELISA method.Also polymerase chain reaction (PCR)was performed for quali-tative detection of Escherichia coli specific beta galactosidase gene BG.Results Compared with T1 , Plasma D-LA level in two groups at T2-T4 were increased gradually and it was significantly higher in group GA than in group GE at T2-T4 with significant difference (P <0.05).The Escherichia coli DNA test was negative at T1 ,the positive rate of Escherichia coli DNA gradually increased,and it was significantly higher in group GA than in group GE at T4 with significant difference(P <0.05).Conclusion Compared with the general intravenous anesthesia, general anesthesia combined with epidural anesthesia may relieve the intestinal barrier injury in patients with obstructive jaundice after surgery.

Objective:To explore the influence of embryonic stem cells-derived neural stem cells on the proliferation and secretion cytokines of bone marrow-derived macrophages. Methods:Mouse bone marrow derived macrophages were isolated and cultured in L929 medium. After macrophages were treated with NSCs supernatant for 3 days,SRB method was used to detect the proliferation of macrophages. The phagocytosis of macrophages were detected by incubating with RFP-Beads for 1 h. Meanwhile,the expression of TNF-α and IL-1β were detected by ELISA. Results:NSCs were successfully induced from ESC. In control group and NSC group, the proliferation rate of macrophages were 100 % and (126. 29 ± 5. 41)%,the phagocytosis rate were (70. 23 ± 2. 57)% and (90. 32 ± 8. 49)%. Compared to the control group,the levels of IL-6,IL-1βin macrophage treated with NSCs decreased (P<0. 05). Conclusion:ESC-derived NSCs can promote the proliferation and phagocytosis of bone marrow-derived macrophage, and suppress the secretion of pro-inflammatory cytokines.

Objective To explore the risk factors influencing the prognosis by analyzing clinical data of patients with acute paraquat intoxication, and to assess the prognostic values of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, and Acute Kidney Injury Network (AKIN) stage.Methods The clinical data of patients with acute paraquat intoxication admitted into the First People's Hospital of Xianyang City during October 2005 to May 2015 were retrospectively analyzed.The patients were divided into death group and survival group according to 28-day outcome after poisoning.The gender, age, body weight index, toxin dose, time elapsed from poisoning to gastric lavage, time elapsed from poisoning to hemoperfusion (HP), times of HP treatment, white blood cell count (WBC), alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK) were determined at admission.Arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), arterial lactate (Lac), and APACHE Ⅱ score, SOFA score and AKIN stage were recorded and compared between two groups.The receiver operating characteristic (ROC) curve was plotted for APACHE Ⅱ score, SOFA score and AKIN stage to analyze the prognostic value for patients with acute paraquat intoxication.Results There were 118 cases in total,with 64 survivors and 54 deaths in 28 days, and the fatality rate was 45.76％.Compared with survival group, the toxic dose (mL: 66.29 ± 27.40 vs.29.16 ± 19.40), time elapsed from poisoning to gastric lavage (minutes: 60.37 ± 26.68 vs.41.17± 14.82), WBC count (× 109/L: 16.86±2.77 vs.10.25 ± 2.60), ALT (U/L: 53.94± 10.85 vs.36.40±9.21),SCr (μmol/L: 159.69±42.85 vs.81.73±34.40) at admission as well as Lac (mmol/L: 3.06± 1.33 vs.1.71 ±0.88),APACHE Ⅱ score (6.46±2.38 vs.3.31 ± 1.51), SOFA score (3.31 ± 1.06 vs.2.21±0.76) 48 hours after admission were significantly higher in the death group (all P ＜ 0.01).PaO2 and PaCO2 48 hours after admission were significantly lower in death group than those in the survival group [PaO2 (mmHg, 1 mmHg =0.133 kPa): 64.07± 13.04 vs.75.40 ± 13.27, PaCO2 (mmHg): 26.20 ± 8.89 vs.31.25 ± 6.29, both P ＜ 0.01].There were 18, 15, 11 and 10 patients in AKIN 0, 1, 2, 3 stage 48 hours after admission respectively in death group, and 38, 15, 7, 4 in survival group.The difference between two groups was statistically significant (P ＜ 0.01).There were no statistically significant differences in gender, age, body mass index, time elapsed from poisoning to HP, levels of HP, and AST, TBil, BUN and CK at admission between the two groups.At 48 hours after admission, the area under the ROC curve (AUC) of APACHE Ⅱ score predicting the prognosis of patients with acute paraquat poisoning was 0.875 [95％ confidence interval (95％CI) =0.814-0.935, P =0.000].When the cut-off point of APACHE Ⅱ score was 4, the sensitivity and specificity were 79.6％ and 79.7％, and the best Youden index was 0.593.The AUC of SOFA score was 0.776 (95％CI=0.692-0.859, P =0.000).When the cut-off point of FOFA score was 3, the sensitivity was 72.2％, the specificity 67.2％, and the best Youden index 0.394.The AKIN stage of ROC curve had an area of 0.656 (95％CI =0.556-0.755, P =0.004).When the cut-off point of AKIN stage was 1, the sensitivity was 66.7％, the specificity was 59.4％, and the best Youden index was 0.261.Conclusions Amount of the poison, time elapsed from poisoning to gastric lavage, and WBC, ALT, SCr at admission as well as PaO2, PaCO2 and Lac 48 hours after admission are the risk factors for prediction of the prognosis of acute paraquat intoxication.APACHE Ⅱ score, SOFA score and AKIN stage can be used to assess the prognosis of acute paraquat poisoning, and APACHE Ⅱ score is better than SOFA score and AKIN stage.

Humans ; Imidazoles ; poisoning ; Neonicotinoids ; Nitro Compounds ; poisoning