Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

The 2021 version of the Baveno Ⅶ consensus on portal hypertension and the 2023 guidelines from the European Association for the Study of the Liver define recompensated cirrhosis as the restoration and stabilization of liver function, improvement of liver fibrosis, and absence of decompensated cirrhosis for a long time following effective treatment of the underlying etiology of cirrhosis. Recompensated cirrhosis has become an important research direction in the field with the gradually increasing number of these patients. Temporary recompensation, stable recompensation, and long-term recompensation are the three stages into which patients with cirrhosis are divided, based on varying recompensation stages. Clinical characteristics and prognosis are significantly different among different stages. Patients in the temporary compensation stage have significant fluctuations in their condition and poor stability, with a high risk of recurrent complications. The prognosis of patients in the stable recompensation stage is significantly affected by the cause and the type of initial decompensation event, while the condition of patients in the long-term recompensation stage is more stable, and the long-term prognosis is close to that of compensated cirrhosis. This article aims to summarize and explore the recompensation rates at different stages of liver cirrhosis, the occurrence risk of various complications and liver cancer, and long-term management and treatment following recompensation, providing new directions for future research in this field.

The 2021 version of the Baveno Ⅶ consensus on portal hypertension and the 2023 guidelines from the European Association for the Study of the Liver define recompensated cirrhosis as the restoration and stabilization of liver function, improvement of liver fibrosis, and absence of decompensated cirrhosis for a long time following effective treatment of the underlying etiology of cirrhosis. Recompensated cirrhosis has become an important research direction in the field with the gradually increasing number of these patients. Temporary recompensation, stable recompensation, and long-term recompensation are the three stages into which patients with cirrhosis are divided, based on varying recompensation stages. Clinical characteristics and prognosis are significantly different among different stages. Patients in the temporary compensation stage have significant fluctuations in their condition and poor stability, with a high risk of recurrent complications. The prognosis of patients in the stable recompensation stage is significantly affected by the cause and the type of initial decompensation event, while the condition of patients in the long-term recompensation stage is more stable, and the long-term prognosis is close to that of compensated cirrhosis. This article aims to summarize and explore the recompensation rates at different stages of liver cirrhosis, the occurrence risk of various complications and liver cancer, and long-term management and treatment following recompensation, providing new directions for future research in this field.

Neonatal hyperammonemia has great damage to the central nervous system, which can lead to severe disability and even death.Early reduction of blood ammonia and shortening the duration of hyperammonemia coma can improve the poor prognosis of the central nervous system.Renal replacement therapy can reduce blood ammonia quickly and effectively which is an important treatment for neonatal hyperammonemia.Common kidney replacement therapies include peritoneal dialysis, intermittent hemodialysis, continuous renal replacement therapy and hybrid therapy.This review aims to elaborate the indications of renal replacement therapy, the advantages and disadvantages of various renal replacement therapy modes in the treatment of neonatal hyperammonemia and hybrid therapy.

Allergens ; Asthma ; Humans ; Rhinitis, Allergic ; Seasons ; Skin Tests

Objective:To investigate the clinical characteristics of neonatal congenital tongue base cyst.Methods:This retrospective study involved 35 neonates with congenital tongue base cyst diagnosed in the neonatal intensive care unit (NICU) of Xi'an Children's Hospital from June 2013 to December 2019. General information, clinical manifestations, supplementary results, treatment and prognosis of these babies were described.Results:(1) The median age at the onset of the disease was 12.5 (0~28) d and the median age at admission was 15 (0~28) d for these babies. The main clinical manifestations were laryngeal stridor (28/35, 80.0%), inspiratory dyspnea and crying, especially when feeding (26/35, 74.3%) and choking and spitting with feeding (23/35, 65.7%). (2) Among the 35 cases, 15 (42.9%) required emergency endotracheal intubation due to significant dyspnea when were admitted to the NICU and five out of them were considered for having tongue base mass under laryngoscopy, while the other 10 cases underwent bedside electronic laryngoscopy after endotracheal intubation, in which space-occupying lesions were found. Tongue base cyst was considered in seven cases with laryngeal stridor complicated by protracted pneumonia using fiberoptic bronchoscopy. The other 13 cases were examined by electronic laryngoscope and considered as tongue base cyst. Thirty-five cases underwent cervical ultrasound and only five of them were considered as tongue base tumor. Thirty-two cases underwent cervical CT scan and only two of them were normal. Three cases were found to have tongue base cyst by cranial MRI. (3) Thirty-four cases were treated by radiofrequency ablation assisted with self-retaining microlaryngoscope and general anesthesia, while the other one firstly received puncture and drainage under direct laryngoscope due to the difficult intubation because of the huge tongue base cyst and then underwent surgery when stable. Only one case (2.9%) relapsed after surgical treatment during regular follow-up.Conclusions:Neonatal congenital tongue base cyst has an early onset and atypical clinical manifestations. Electronic laryngoscopy/fiberoptic bronchoscopy combined with neck CT or MRI examination should be performed promptly in patients with laryngeal stridor and inspiratory dyspnea to facilitate the accurate diagnosis and timely surgery is required for.

Patients with chronic hepatitis B (CHB) often have immune-mediated liver injury, and it is considered that the interaction between viral infection and immune response is an important cause of disease progression. CHB can progress to liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma (HCC). This article reviews the discovery of T helper 17 (Th17) cells and regulatory T (Treg) cells, describes their own features, and elaborates on their role and mechanism of action in maintaining the stability of the immune system. This article also analyzes the role of Th17/Treg cell imbalance in CHB, liver fibrosis, liver cirrhosis, and HCC and points out that Th17/Treg cell imbalance may promote the aggravation of HBV-related liver diseases.

The JAK/STAT/SOCS signaling pathway can mediate a variety of cytokines involved in inflammation, tumor, and autoimmune diseases and it also plays an important role in hepatitis B virus (HBV) infection-related liver diseases. This article briefly reviews the structure and signal pathway regulation of JAK-STAT and SOCS and elaborates on their role in the development and progression of HBV-related chronic hepatitis B, liver cirrhosis, liver failure, and hepatocellular carcinoma. The final analysis shows that the JAK/STAT/SOCS signaling pathway is dysregulated in HBV-related liver disease and is involved in the development and progression of the disease, and it may even influence the treatment and prognosis of the disease.

Objective To analyze clinicopathological characteristics and the potential risk-related factors of female breast hyperplasia in different age groups.Method From Jan 2015 to Dec 2016,patients diagnosed with breast hyperplasia in 12 hospitals were evaluated.All patients completed the self-designed questionnaires on women'health,including basic demographic information,clinic examination information,radiologic information and pathologic results.The patients were divided into a young group (＜ 45 years old) and an elderly group (from 45 to 75 years old).Results There were 3 684 cases of breast hyperplasia,including 2 291 cases in young group and 1 393 cases in elder group,respectively Clinically breast pain type were most commonly observed in both young and older groups (50.3％ vs.42.7％,P ＜ 0.001).While pathological research based on biopsy showed that breast adenopathy were the most common changes in both groups (67.9％ vs.61.7％,P ＜0.001).More breast cancer cases were identified in elder group than that in young group,especially in clinically lump type patients (9.4％ vs.4.2％,P ＜ 0.001).Compared with elder group,patients in young group have different distribution characteristics regarding to fertility factors,lifestyle factors and psychology scale including anxiety and depression.Conclusion Distributions of clinicopathological characteristics and risk factors of female breast hyperplasia differ across different age groups.

OBJECTIVE： To compare plasma protein binding rate of cajanonic acid A with different species of plasma. METHODS：Using UPLC-MS/MS as the detection means. Plasma protein binding rate of low， medium and high concentrations of cajanonic acid A （2.5， 5， 20 μg/mL） with rats， rabbits and human plasma were determined by ultrafiltration method. The chromatographic conditions included that Waters BEH C18 as chromatographic column， WatersVanGuard BEH C18 as guard column， mobile phase consisted of ultrapure water solution containing 0.01％ formic acid （solvent A） and acetonitrile solution of 0.01％ formic acid （solvent B） gradient elution， at the flow rate of 0.15 mL/min， column temperature of 30 ℃， sample size of 2 μL. Mass spectrum condition included that ESI， negative ion mode acquisition， capillary voltage of 1.5 kV， cone voltage of 30 V， ion source temperature of 100 ℃， desolvent gas temperature of 400 ℃， cone gas flow of 50 L/h， desolvent gas flow of 800 L/h， scanning range of m/z 50→1 200. RESULTS： At the concentration of 2.5， 5 and 20 μg/mL， the plasma protein binding rates of cajanonic acid A were （75.63±0.90）％， （98.30±0.03）％ and （99.42±0.01）％ in the rats plasma； （79.61±1.08）％， （98.48±0.10）％ and （99.42±0.03）％ in rabbits plasma （n＝3）； （76.74±1.22）％， （97.99±0.11）％ and （99.37±0.01）％ in human plasma （n＝3）. At the concentration of 2.5 μg/mL， plasma protein binding rates of cajanonic acid A in plasma of rats and human were significantly lower than that in plasma of rabbits （P＜0.05）. CONCLUSIONS： The plasma protein binding rate of 5，20 μg/mL cajanonic acid A with rats， rabbits and human plasma are higher than that of 2.5 μg/mL cajanonic acid A. There is significant difference in plasma protein binding rate of 2.5 μg/mL cajanonic acid A with different species of plasma，and there is no significant difference in plasma protein binding rate of 5， 20 μg/mL cajanonic acid A with different species of plasma.