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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

To develop an intelligent lower limb rehabilitation instrument which could realize the quantification and visualization of lower limbs' raising angle and frequency, using the smart client to realize the remote control, autonomous data acquisition and the establishment of database. Doctors had the access to the database in order to adjust the rehabilitation program in time to meet the individual requirement. We realized the design of intelligent lower limb instrument based on the Andriod smartphone, which is suitable for clinical and family use.
Computers ; Databases, Factual ; Humans ; Leg ; Mobile Applications ; Rehabilitation ; instrumentation ; Smartphone

OBJECTIVETo investigate the interval time to canceration, clinicopathological characteristics and prognostic factors of carcinoma in remnant stomach (CRS) in patients with primary benign diseases or primary malignant tumors.

METHODSBased on the criteria of the definition of CRS proposed by Japanese Gastric Cancer Association in 2017, a retrospective analysis was conducted on clinicopathological characteristics of patients diagnosed with CRS at Peking University Cancer Hospital from March 1992 to March 2017. Between patients with primary benign diseases (CBS-B group) and primary malignant tumors (CBS-M group), continuous variables were compared using the Student's t-test or the Mann-Whitney U test; categorical variables were compared using the chi-square test or Fisher's exact test. Spearmen-Rho was used to examine correlation. Survival was estimated and compared using Kaplan-Meier methods. Cox proportional hazards regression was applied to identify independent prognostic factors. Area under ROC curve(AUC) was used to evaluate and compare prediction accuracy.

RESULTSA total of 89 patients were included in the study with a male: female ratio of 5.4 to 1.0. The male: female ratio in CRS-B (n=46) and CRS-M (n=43) group was 14.3 to 1.0 and 2.9 to 1.0 respectively with significant difference (χ=6.091, P=0.019). The interval time to canceration in CRS-B and CRS-M group was 342(36-576) months and 47(12-360) months respectively with significant difference (t=8.887, P=0.000). The interval time to canceration was correlated with the first operative procedure in CRS-B group (r=0.398, P=0.006), while interval time to canceration was correlated with the age at the first operation in CRS-M group (r=0.337, P=0.027). After differentiating the pathological findings of the first operative sample and the second operative sample, 27 patients presented recurrence and 15 patients had new cancer, and the corresponding interval time to canceration was 46(12-132) months and 60(12-360) months respectively with significant difference (t=5.652, P=0.023). In CRS-B group, location of stump carcinoma in gastric intestinal anastomosis, gastric anastomosis, and non-anastomosis area was found in 60.9%(28/46), 23.9%(11/46) and 15.2%(7/46) respectively, and the corresponding percentage in CRS-M group was 39.5%(17/43), 16.3%(7/43) and 44.2%(19/43) respectively without significant difference (χ=4.726, P=0.096). Among 77 patients with radical gastrectomy, the overall surgical complication rate was 20.8%(16/77), including 8 cases of infection and 7 cases of respiratory system diseases. The 3-year survival rate was 78.4% and 62.6% in CRS-B and CRS-M group respectively with significant difference (χ=3.969, P=0.046), indicating better prognosis of CRS-B patients. The AUC for the lymph nodes ratio and N staging was 0.725 and 0.639 respectively. Multivariate analysis showed the pathological T staging was an independent risk factor of prognosis (HR=1.192, 95%CI:1.032-1.376, P=0.017).

CONCLUSIONSMen have more CRS than women. The interval time to canceration is correlated to the first operative procedure for CRS-B patients, while it is correlated to the age at the first operation for CRS-M patients. The major location of CRS is in the gastrointestinal anastomosis for CRS-B patients and in non-anastomosis area for CRS-M patients. Main postoperative complications include respiratory and infectious complications. Pathological T staging is an independent prognostic risk factor for CRS patients.

Cancer Care Facilities ; Factor Analysis, Statistical ; Female ; Gastrectomy ; Gastric Stump ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Male ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Survival Rate ; Universities

OBJECTIVETo compare the short-term safety and costs between laparoscopic assisted or totally laparoscopic uncut Roux-en-Y and Billroth II((BII() + Braun reconstruction after radical gastrectomy of distal gastric cancer.

METHODSClinical data from our prospective database of radical gastrectomy were systematically analyzed. The patients who underwent laparoscopic gastrectomy with uncut Roux-en-Y or BII(+ Braun reconstruction between March 1st, 2015 and June 30th, 2017 were screened out for further analysis. Both the reconstructions were completed by linear staplers. Uncut Roux-en-Y reconstruction was performed with a 45 mm no-knife linear stapler (ATS45NK) on the afferent loop below the gastrojejunostomy. Continuous variables were compared using independent samples t test or Mann-Whitney U. The frequencies of categorical variables were compared using Chi-squared or Fisher exact test.

RESULTSEighty-one patients were in uncut Roux-en-Y group and 58 patients were in BII(+Braun group. There were no significant differences between uncut Roux-en-Y group and BII(+Braun group in median age (56.0 years vs. 56.5 years, P=0.757), gender (male/female, 52/29 vs. 46/12, P=0.054), history of abdominal surgery (yes/no, 10/71 vs. 4/54, P=0.293), neoadjuvant chemotherapy (yes/no, 21/60 vs. 11/47, P=0.336), BMI (thin/normal/overweight/obesity, 2/49/26/3 vs. 3/39/14/2, P=0.591), NRS 2002 score (1/2/3/4, 58/15/5/3 vs. 47/5/3/3, P=0.403), pathological stage (0/I(/II(/III(, 3/41/20/17 vs. 1/28/13/16, P=0.755), median tumor diameter in long axis (2.5 cm vs. 3.0 cm, P=0.278), median tumor diameter in short axis (2.0 cm vs. 2.0 cm, P=0.126) and some other clinical and pathological characteristics. There were no significant differences between uncut Roux-en-Y group and BII(+Braun group in morbidity of postoperative complication more severe than grade I([12.3% (10/81) vs. 17.2% (10/58), P=0.417], morbidity of anastomotic complication [1.2%(1/81) vs. 0, P=1.000] or hospitalization costs [(94000±14000) yuan vs.(95000±16000) yuan, P=0.895]. The median first time to liquid diet (57.1 hours vs. 70.8 hours, P=0.017) and median postoperative hospital stay (9 days vs. 11 days, P=0.003) of the patients in uncut Roux-en-Y group were shorter than those in BII(+Braun group.

CONCLUSIONLaparoscopic assisted or totally laparoscopic uncut Roux-en-Y reconstruction after radical gastrectomy of distal gastric cancer is safe and feasible with better recovery than BII(+Braun reconstruction.

Anastomosis, Roux-en-Y ; Databases, Factual ; Female ; Gastrectomy ; Gastroenterostomy ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Prospective Studies ; Stomach Neoplasms ; surgery ; Treatment Outcome