ObjectiveTo investigate the effects of Liuwei Dihuangwan on mammalian target of rapamycin （mTOR）-mediated synaptic plasticity in the prefrontal cortex-hippocampus circuit in the rat model of valproic acid （VPA）-induced autism spectrum disorder （ASD） and to explore its potential mechanism for reducing behavioral abnormalities in ASD rats. MethodsThirteen SD pregnant rats were randomized into the VPA group （10 rats） and the control group （3 rats）. On gestational day 13， the VPA group was intraperitoneally injected with VPA solution （600 mg·kg^-1）， while the control group was injected with an equal volume of normal saline. Male pups of 21 days old from both groups underwent behavioral tests to screen the ASD model rats （32 rats）. These rats were then randomly assigned to the model （distilled water）， vitamin D （1 480 U·kg^-1）， low-dose （0.75 g·kg^-1） Liuwei Dihuangwan， and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan groups， and normal male pups were selected as the blank group （distilled water）， with 8 rats in each group. Each group was treated with the corresponding drug or an equal volume of distilled water via gavage daily. After drug administration， behavioral tests were conducted again， followed by anesthesia and tissue collection. Nissl staining was carried out to observe the morphological changes of neurons in the prefrontal cortex and hippocampus. Transmission electron microscopy was used to observe changes in hippocampal synaptic structure. Immunohistochemistry and Western blot were employed to determine the expression of mTOR， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the prefrontal cortex， as well as synaptophysin-1 （SYP-1）， postsynaptic density 95 （PSD95）， and N-methyl-D-aspartate receptors （NMDARs） in the hippocampus. ResultsCompared with the control group， the model group exhibited severe growth retardation and developmental deformities， with abnormal behavioral performance and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus. Compared with the model group， all treatment groups showed reduced behavioral abnormalities and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus， with the most significant effects in the high-dose Liuwei Dihuangwan group. Immunohistochemistry and Western blotting results showed that compared with the control group， the model group exhibited significantly increased protein levels and phosphorylation ratios of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex （P<0.05， P<0.01）， and decreased protein levels of SYP-1 and PSD95 and increased protein level of NMDARs in the hippocampus （P<0.01）. Compared with those in the model group， the protein levels of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.05）， and the p-mTOR/mTOR， p-Akt/Akt， and p-PI3K/PI3K ratios in the prefrontal cortex declined in the vitamin D group （P<0.05）. The high-dose Liuwei Dihuangwan group showed a reduction in p-PI3K/PI3K ratio （P<0.05）. The protein level of SYP-1 and PSD95 in the hippocampus increased in the vitamin D， low-dose Liuwei Dihuangwan， and high-dose Liuwei Dihuangwan groups （P<0.05， P<0.01）， while the protein level of NMDARs decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.01）. ConclusionLiuwei Dihuangwan significantly reduces VPA-induced ASD-like behaviors and enhances the regeneration and repair of neurons in the prefrontal cortex and synaptic structures in the hippocampus by downregulating of PI3K/Akt/mTOR expression in the prefrontal cortex， upregulating SYP-1 and PSD95 expression in the hippocampus， and inhibiting NMDARs expression.

Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.

Ulcerative colitis (UC) is an idiopathic and relapsing inflammatory bowel disease. Previous research has uncovered that macrophages play an indispensable role during the progression of UC. Macrophages in the mucus are stimulated via upstream cytokines or ligands from microorganisms and secrete numerous inflammatory cytokines to exacerbate the colitis. Consequently, precisely modulating macrophages has been an intriguing strategy in UC treatment recently. With the superiority of high efficiency, less toxicity, and sustained release, exploring macrophage-targeted nanodrugs has already become a mainstream approach in UC therapeutics. This review summarizes the strategy of targeting macrophages with nanodrugs and the potential biological mechanisms for UC treatment.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Objective:To observe the proteomic changes in vitreous fluid samples from patients with rhegmatogenous retinal detachment combined with choroidal detachment (RRDCD).Methods:A prospective cross-sectional clinical study. Vitreous fluid samples were collected from 35 patients with RRDCD (RRDCD group) and 40 patients with rhegmatogenous retinal detachment (RRD group) who were diagnosed at Wuhan Aier Eye Hospital between November 2021 and December 2023. Prior to vitrectomy, 0.3-0.5 ml of vitreous fluid was collected from the affected eyes. Differentially expressed proteins were analyzed using Data-Independent Acquisition (DIA). Three of these proteins were randomly selected for validation using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analyses, including gene ontology functional enrichment and kyoto encyclopedia of genes and genomes pathway enrichment, were performed to explore the functions of the differentially expressed proteins.Results:Significant differences were observed between the RRDCD and RRD groups in intraocular pressure ( t=-12.795), the number of retinal tears ( t=4.601), the extent of retinal detachment ( χ2=39.642), axial length ( t=0.840), postoperative proliferative vitreoretinopathy incidence ( χ2=4.730), single-surgery reattachment rate ( χ2=7.717), and best-corrected visual acuity ( t=7.033) at 6 months postoperatively ( P<0.05). A total of 237 differentially expressed proteins were identified between the RRDCD and RRD groups, with 63 upregulated and 174 downregulated. These proteins were involved in pathways such as extracellular matrix-receptor interaction, complement activation, coagulation, and lysosomal pathways. ELISA validation results showed that the expression trends of the three selected proteins in the RRDCD and RRD groups were consistent with the DIA proteomic analysis. Compared to the RRD group, proteins such as fibrin, coagulation factors, cathepsins, and trypsin inhibitors were significantly upregulated in the RRDCD group. Conclusions:The protein expression profile in vitreous fluid samples from RRDCD patients show significant alterations compared to the RRD group. These differential changes suggest that RRDCD is closely associated with complement and coagulation cascade activation, lysosomal pathways, and extracellular matrix remodeling.

Ulcerative colitis (UC) is an idiopathic and relapsing inflammatory bowel disease. Previous research has uncovered that macrophages play an indispensable role during the progression of UC. Macrophages in the mucus are stimulated via upstream cytokines or ligands from microorganisms and secrete numerous inflammatory cytokines to exacerbate the colitis. Consequently, precisely modulating macrophages has been an intriguing strategy in UC treatment recently. With the superiority of high efficiency, less toxicity, and sustained release, exploring macrophage-targeted nanodrugs has already become a mainstream approach in UC therapeutics. This review summarizes the strategy of targeting macrophages with nanodrugs and the potential biological mechanisms for UC treatment.

OBJECTIVE To compare the efficacy and safety of icotinib and gefitinib in the treatment of epidermal growth factor receptor （EGFR）-mutated advanced non-small cell lung cancer （NSCLC）. METHODS The data of 146 patients with EGFR- mutant advanced NSCLC of our Hospital from December 2015 to September 2021 were retrospectively analyzed and divided into the gefitinib group （73 cases） and the icotinib group （73 cases） according to the drug use. Patients in the gefitinib group were given 0.25 g of gefitinib tablets once a day orally by single drug or combined with conventional chemotherapy， while patients in the icotinib group were given 125 mg of icotinib hydrochloride tablets three times a day orally by single drug or combined with conventional chemotherapy. Short-term efficacy， progression-free survival （PFS） were observed； Cox regression model was used to analyze the factors affecting the prognosis of patients； the occurrence of ADR were observed in the two groups. RESULTS There was no statistically significant difference in the objective remission rate， disease control rate， and the incidence of grade 1-2 and grade 3-4 adverse drug reactions between the two groups （P＞0.05）； median PFS was significantly better in the icotinib group than in the gefitinib group （P＝0.048）. Results of subgroup analysis based on patients basic information showed that compared with the gefitinib group， PFS of female [HR＝0.57，95%CI（0.34，0.96），P＝0.031] and non-brain metastatic patients [HR＝0.58，95%CI（0.36，0.91），P＝0.017] in icotinib group were prolonged significantly. Results of regression model analysis showed that EGFR19 exon Del mutation [HR＝0.50， 95%CI（0.25，1.00）， P＝0.049]， EGFR21 exon L858R mutation [HR＝0.44， 95%CI（0.21，0.89）， P＝0.022] and icotinib treatment [HR＝0.65， 95%CI （0.44，0.96）， P＝0.030] were influential factors for prognosis. CONCLUSIONS The short-term efficacy and safety of icotinib and gefitinib in the treatment of EGFR- mutant advanced NSCLC are comparable， but icotinib can significantly prolong the patients’ PFS； EGFR19 exon Del， EGFR21 exon L858R mutations and icotinib treatment are factors affecting patients’ prognosis.

Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.

【Objective】 To establish a method for detecting human immunoglobulin Fc function based on surface plasmon resonance technology. 【Methods】 Based on the characteristic that FcγRI can be binded to the Fc segment of IgG, the affinity constant of the sample was detected by surface plasmon resonance, and its Fc function was the KD ratio of the sample to the standard. The method was validated for specificity/specificity, precision and robustness. The method and the pharmacopoeia method were used to detect the Fc function of 30 human immunoglobulins, and the correlation and consistency of the detection results were analyzed. 【Results】 The method validation results showed that this method has strong specificity/specificity (t values were 0.15, 0.22, both P>0.05), good precision (CV value 5.37%~10.69%) and good robustness (CV value 10.06%). The detection results of this method and the pharmacopoeia method have high correlation (r=0.96, P<0.05) and high consistency (Bias-2.060, 95% Limits of Agreement-5.628~1.508). 【Conclusion】 A method for detecting human immunoglobulin Fc function based on surface plasmon resonance has been successfully established.

Objective:To evaluate the safety and efficacy of LVIS stent-assisted coil embolization in the acute phase of ruptured intracranial aneurysms.Methods:The clinical data of 55 patients with ruptured intracranial aneurysm treated with LVIS stent-assisted coil embolization admitted to Zhongshan Hospital of Xiamen University from January 2016 to December 2018 were analyzed retrospectively. The general data, the characteristics of aneurysms and the occurrence of perioperative complications of the patients were collected. The clinical prognosis of the patients at discharge and 6 months of follow-up was recorded. The Glasgow prognosis score (GOS) was graded as good (5), average (3-4), and poor (1-2), and the cerebral angiography results were recorded immediately after embolization and 6-month follow-up. The aneurysm occlusion was assessed by Raymond grade, Raymond Ⅰ was complete obliteration, Ⅱ was residual neck and Ⅲ was residual aneurysm.Results:All 55 patients received LVIS stent-assisted coil embolization within 72 hours of ruptured intracranial aneurysms, and all stents were released successfully, including 16 males (29.1%) and 39 females (70.9%). The median age was 53 (24-80) years old. Anterior circulation aneurysms were found in 49 patients (89.1%) and posterior circulation aneurysms in 6 patients (10.9%). According to Hunt-Hess classification, there were 43 patients with grade Ⅰ-Ⅱ (78.2%), 7 patients with grade Ⅲ (12.7%) and 5 patients with grade Ⅳ-Ⅴ (9.1%). The first digital subtraction angiography (DSA) examination of 55 patients after embolization showed that 41 patients had complete obliteration of aneurysms and 14 had residual neck; and the smaller the aneurysm was, the higher the rate of complete obliteration after embolization was. The proportion of small aneurysms (maximum diameter ≤ 7 mm) in the complete obliteration group was significantly higher than that in the neck residual group (100.0% vs. 64.3%, P < 0.01). Among the 55 patients, there was 1 patient suffered from in-stent thrombosis during embolization, 1 patient suffered from distal vascular thrombosis induced by plaque shedding during embolization, 1 patient suffered from vasospasm during embolization, and 1 patient suffered from postoperative distal cerebral hemorrhage after embolization. In 2 dead patients, 1 died of cardiogenic disease and 1 died of respiratory failure caused by severe pneumonia. At discharge, the prognosis was good in 40 patients, average in 10 patients, and poor in 5 patients; and the higher the Hunt-Hess grade at admission, the worse the prognosis. The proportion of patients with Hunt-Hess grade Ⅰ-Ⅱ at admission in the good prognosis group was significantly higher than that in the general prognosis group and the poor prognosis group (90.0% vs. 50.0%, 40.0%, P < 0.01). Of the 55 patients, 39 completed clinical prognosis and cerebral angiography 6 months after embolization for follow-up. All patients had GOS no less than 3, including 32 patients with complete obliteration of aneurysm, 4 with residual neck and 3 with residual aneurysm. The smaller the aneurysm, the higher the rate of complete obliteration at 6-month follow-up was. The proportion of small aneurysm in the complete obliteration group was significantly higher than that in the residual neck group and the residual aneurysm group (100.0% vs. 75.0%, 33.3%, P < 0.01). There was no rebleeding or ischemic complication at 6-month follow-up. Conclusions:LVIS stent assisted coil embolization is safe, effective and feasible in the acute stage of ruptured intracranial aneurysms. Standardizing antiplatelet therapy and dense packing of aneurysms during embolization are the key to reduce bleeding and ischemic complications.