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 sterile electrode acupuncture needle for single use is an innovative product that combines traditional acupuncture with modern electronic technology, and it has obtained Class Ⅱ medical device registration certificate. This acupuncture device consists of a needle body and a handle. The diameter of the needle body ranges from 0.16 mm to 0.55 mm, and the length from 7 mm to 150 mm. The spiral spray technology is adopted to modify the micron-level insulating coat on stainless steel needle body. The needle holder is connected to the electroacupuncture device (conductive), the micro-film insulated needle body (non-conductive) and the membrane-free needle tip (conductive) can provide a precise electrical stimulation for different tissue layers of acupoints (such as deep nerves and fascia). The intradermal stimulation test, cytotoxicity test and hypersensitivity reaction test have showed a favorable biocompatibility, laying a solid and reliable safety for clinical application. This acupuncture device is suitable for the in-depth invasive stimulation at the sites of human body surface in combination with electroacupuncture equipment in medical institutions.
Humans ; Needles ; Acupuncture Therapy/instrumentation* ; Electrodes ; Equipment Design ; Electroacupuncture/instrumentation* ; Acupuncture Points ; Animals

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Objective : To investigate the factors affecting the outcome of high-risk human papillomavirus ( HR- HPV) infection in patients with normal cervix examined by colposcopy in Hefei area and the relationship between persistent HR-HPV infection and cervical cytology． Methods : Data of colposcopy patients were collected from 478 HR-HPV infected patients with normal cervix through colposcopy．Their age，number of sexual partners，contracep- tive methods and other relevant basic information were recorded．Vaginal interferon use，HR-HPV infection at year 1 and year 2，and cervical liquid-based cytology test ( LCT) results were tracked，univariate and multivariate ana- lyses were performed based on basic information，and ROC curves were plotted． Results : The HR-HPV clearance rate at 1 year was 59. 41% ，and the clearance rate at 2 years was 66. 75%．The other 12 types of infection ( 31， 33，35，39，45，51，52，56，58，59，66，68) were more common than the 16 and 18 types．Univariate and mult- ivariate analyses showed that age＞50 years，number of sexual partners ≥2，and history of cervical conectomy in- creased the risk of persistent HR-HPV infection ( χge = 21. 676，P ＜0. 001; χumber of sexual partners = 8. 262，P =0. 004; χistory of cervical conectomy = 11. 267，P = 0. 001 ) ． The risk of HR-HPV infection was significantly lower when condom or vaginal interferon was used ( χondom use = 10. 885，P = 0. 001; χnterferon use = 4. 099，P = 0. 043) ．The area under the ROC curve (AUC) of combined diagnosis of HR-HPV persistent infection was higher than that of single diagnosis，and the AUC of combined diagnosis was 0. 737．Persistent HR-HPV infection was an independent risk factor for abnormal LCT，and the AUC predicted by the model was 0. 755．No cancer was found in patients with persistent HR-HPV infection for 2 years，and the proportion of abnormal LCT was higher than that in patients with negative HR-HPV．The difference was statistically significant ( χ2 = 39. 64，P＜0. 001) ． Conclusion The combined ROC model constructed for patients＞50 years old，with multiple sexual partners，history of cervical surgery， no vaginal interferon use，and no condom use has certain value in predicting persistent HR-HPV infection，and per- sistent HR-HPV infection has predictive value in predicting LCT abnormalities．

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

Objective The aim of this study was to explore the predictive value of the systemic inflammatory immune nutri-tion score(SIINS)for the prognosis of immunotherapy for advanced gastric cancer.Methods A retrospective analysis was conducted on the clinical data of 202 patients with advanced gastric cancer who received treatment with programmed death-1(PD-1)inhibitors at the Harbin Medical University Cancer Hospital from October 2018 to July 2022.The LASSO regression analysis was used to screen prognostic indicators,construct SIINS indicator,determine the optimal cutoff value for predicting prognosis using subject operating characteristic curves,and divide patients into the high SIINS and low SIINS groups.Independent prognostic factors for overall survival(OS)were determined using univariate and multivariate Cox regression analyses.Results Four indicators,including lymphocyte count,lactate dehydrogenase,and neutrophil lymphocytes,were selected to construct the SIINS index.The prognosis of patients in the high SIINS group was significantly lower than that in the low SIINS group(P<0.05).The results of the multifactorial Cox regression a-nalysis showed that the Eastern Cooperative Oncology Group(ECOG)score,Geriatric Nutritional Risk Index(GNRI),SIINS,treatment regimen,and number of treatment lines(P<0.05)could serve as the independent predictive prognosis of immunotherapy for advanced gastric cancer.Conclusion SIINS can predict the prognosis of patients with advanced gastric cancer treated with PD-1 inhibitors.

The theory of"spleen and stomach deficiency and excess transformation"originates from Huangdi Neijing,which is based on the five elements theory.It systematically elucidates the physiological interconnections and pathological transmission relationships among spleen,stomach,and the five zang and six fu viscera.This theory was continuously developed and refined by later physicians.It was first systematically summarized and deepened by LI Dongyuan in his work Piwei Lun,which elaborates on the pathological transmission relationships of other zang-fu viscera after spleen and stomach deficiency.From the perspective of LI Dongyuan's theory of"spleen and stomach deficiency and excess transformation",this paper discusses the pathological relationships between spleen-earth,lung-metal,and kidney-water,and proposes that spleen-earth deficiency is the pathological basis for the onset of allergic rhinitis.Based on the pathological evolution following spleen-earth deficiency,the traditional Chinese medicine syndromes of allergic rhinitis were categorized into three types:earth deficiency with metal weakness,earth dryness with metal desiccation,and water cold with metal excess and earth decline.The treatment of allergic rhinitis should prioritize the spleen-earth,employing acrid and dispersing herbs with light properties to elevate the spleen,sweet-warm and sour-astringent herbs to tonify the spleen,and diuretic and dampness-resolving herbs to activate the spleen,thereby restoring spleen-earth function.Simultaneously,treatment should regulate lung-metal and kidney-water according to different pathological evolutions,incorporating cold-cool or acrid-warm herbs as appropriate,combining cold and warm properties,and treating both the manifestation and root cause of the disease.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

[Purpose]To analyze the incidence and mortality of malignant tumors in cancer regis-tration areas of Heilongjiang Province in 2019 and the trend from 2013 to 2019.[Methods]The incidence and mortality data of malignant tumors reported by the Heilongjiang provincial cancer registries from 2013 to 2019 were collected,and the quality of data was assessed.The crude in-cidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate were calculated.Joinpoint 4.6.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC for the trend analysis from 2013 to 2019.[Results]In 2019,there were 16 732 new cases of malignant tumors in the cancer registration areas of Heilongjiang Province,including 8 639 males and 8 093 females.The crude incidence rate was 295.37/105,with an ASIRC and ASIRW of 167.10/105 and 164.18/105,respectively.There were 10 988 malig-nant tumor deaths,including 6 540 males and 4 448 females.The crude mortality rate was 193.97/105,with an ASMRC and ASMRW of 101.22/105 and 101.66/105,respectively.The inci-dence and mortality of malignant tumors increased rapidly after the age of 55,and the incidence and mortality of males were slightly higher than those of females.The top five malignant tumors of high incidence were lung cancer,female breast cancer,colorectal cancer,liver cancer and thy-roid cancer,and the top five malignant tumors of high mortality were lung cancer,liver cancer,colorectal cancer,stomach cancer and female breast cancer.From 2013 to 2019,the ASIRC of malignant tumors in cancer registration areas increased from 153.08/105 in 2013 to 167.10/105 in 2019,and the ASMRC increased from 92.22/105 in 2013 to 101.22/105 in 2019,but there was no statistical difference in the change trend.[Conclusion]The incidence and mortality of malignant tumors in Heilongjiang Province remain high.Lung cancer,female breast cancer,colorectal can-cer,liver cancer and stomach cancer should be the focus of cancer prevention and control.