ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Objective:To evaluate the role of Kv7.2 in the dorsal root ganglion (DRG) in reduction of paclitaxel-induced neuropathic pain (NPP) by morphine in rats.Methods:SPF healthy male Sprague-Dawley rats, aged 5 weeks, weighing 140-160 g, were randomly selected. This experiment was performed in two parts. Experiment Ⅰ Seventy-two rats were divided into control group (group C), control + morphine group (group C+ M), NPP-1 group (group NPP1) and NPP-1 + morphine group (group NPP1+ M), with 18 animals in each group. Experiment Ⅱ Twenty-four rats were divided into NPP2 group, NPP2+ ML252 group, NPP2+ morphine group (NPP2+ M group), and NPP2 + morphine + ML252 group (NPP2+ M+ ML252 group), with 6 animals in each group. The model of NPP was developed by intraperitoneal injection of paclitaxel 2 mg/kg, once every 2 days for 4 times. After preparation of the model, morphine 5 mg/kg was subcutaneously injected in C+ M group, NPP1+ M group, NPP2+ M group and NPP2+ M+ ML252 group, and potassium channel inhibitor ML252 10 mg/kg was intraperitoneally injected for 7 consecutive days in NPP2+ ML252 group and NPP2+ M+ ML252 group. Six rats were randomly selected from each group on the 1st, 3rd and 7th days after the end of continuous administration in experiment Ⅰ and from each group on the 7th day after the end of continuous administration in experiment Ⅱ for measurement of the mechanical paw withdrawal threshold (MWT) and cold paw withdrawal latency (CWL). At the end of the behavioral assessment, the rats were sacrificed and the DRG was removed for determination of Kv7.2 expression by Western blot. On the 1st day after the end of continuous administration in experiment Ⅰ, the expression of Kv7.2 mRNA in DRG was detected using quantitative real-time polymerase chain reaction, and immunofluorescence was used to detect the co-expression of Kv7.2 with neurons and glial cells in group C.Results:Experiment Ⅰ Compared with C group, the MWT was significantly increased, the expression of Kv7.2 protein and mRNA was up-regulated at each time point ( P<0.05), and no significant change was found in the CWL in C+ M group ( P>0.05), and the MWT was significantly decreased, the CWL was shortened, and the expression of Kv7.2 protein and mRNA was down-regulated at each time point in NPP1 group ( P<0.05). Compared with NPP1 group, the MWT was significantly increased, the CWL was prolonged, and the expression of Kv7.2 protein and mRNA was up-regulated at each time point in NPP1+ M group ( P<0.05). Kv7.2 in DRG was expressed in peptideergic small and medium diameter neurons, non-peptideergic small and medium diameter neurons and large diameter neurons, but not in glial cells. Experiment Ⅱ Compared with NPP2 group, no significant change was found in the expression of MWT, CWL and Kv7.2 in NPP2+ ML252 group ( P>0.05), and the MWT was significantly increased, CWL was prolonged, and the expression of Kv7.2 in DRG was up-regulated in NPP2+ M group ( P<0.05). Compared with NPP2+ M group, the MWT was significantly decreased, CWL was shortened, and the expression of Kv7.2 in DRG was down-regulated in NPP2+ M+ ML252 group ( P<0.05). Conclusions:Down-regulation of Kv7.2 expression in DRG is involved in the reduction of paclitaxel-induced NPP by morphine in rats.

In July 2023， the National Medical Products Administration issued the Measures for the Administration of Standards for Medicinal Products （hereinafter referred to as the Measures）. This article interprets the main content of the Measures， and analyzes its shortcomings as unclear definition of the drug standard code and the goals of drug standard information construction. It is recommended that the national drug regulatory department promptly apply to the standardization authority for the confirmation of the drug standard code “YB” letter， and the drug standard code and numbering rules would be included in the next round of amendments to the Measures. It is necessary to clarify the construction goals of the information system for drug standards at the same time， and build a national drug standard data-sharing platform based on the basic framework of user interface layer， computing processing layer， and data storage layer. Digital drug standards will be free， and access and download services for the public will be provided.

Dry age-related macular degeneration(AMD)is a degenerative disease affecting the macular region of the retina,and aging changes in retinal and choroidal tissues are an important factor in AMD pathogenesis.Cell aging is an irre-versible state of cell cycle arrest triggered by certain physiological processes or stressful injury,affecting a variety of physi-ological and pathological processes.An increasing number of studies have shown that cell aging plays an essential role in the occurrence and development of AMD.This paper reviews the mechanisms of cell aging and its relationship with dry AMD,aiming to provide new ideas for the treatment of dry AMD.

Increasing age is the most important factor for cognitive impairment.Alzheimer disease(AD)and sarcopenia are significant causes of frailty and disability in older adults.It is important to have an in-depth understanding of the relationship between sarcopenia and AD.Studies have reported that sarcopenia often disturbs the secretion of muscle factors,which may increase the risk of developing dementia.In turn,the pathological feature of dementia,such as the de-position of amyloid β-protein(Aβ),amyloid precursor protein(APP)and tau protein in peripheral neurons,may be related to a decline in muscle function.In particular,the deposition of Aβ and APP may eventually lead to movement disorders and disability.Therefore,we hypothesize that AD and sarcopenia may mutually promote each other's pathological develop-ment.This results in exacerbation of clinical and pathological damage,in which myokine and amyloid proteins play impor-tant roles.However,the interrelationship based on amyloid protein and myokine production has not been discussed in de-tail in other reviews.In this paper,we reference and discuss the studies on this topic,and review the common risk factors for sarcopenia and AD and the potential and mechanisms for mutual improvement.

Objective To establish a method for soluble fms-like tyrosine kinase-1(sFlt-1)in human serum based on magnetic nanoparticle chemiluminescence immunoassay and preliminarily evaluate its performance.Methods According to the principle of sandwich plate theory,sFlt-1 in serum reacted with biotinylated anti-sFlt-1 monoclonal antibody and acridinium ester labeled anti-sFlt-1 monoclonal antibody to form an immune complex of biotinylated antibody-antigen-acridinium ester labeled antibody.Through the reaction between biotin and streptavidin,the immune complex was captured by the magnetic nanoparticles coated with streptavidin.The acridinium ester labeled on the immune complex caused chemiluminescence in alkaline H2O2.The chemiluminescence intensity of the immune complex was used to calculate the concentration of sFlt-1 in serum,optimize the concentrations of antibodies,and establish a method for sFlt-l based on magnetic nanoparticle CLIA.The sensitivity,precision,linear range,interference,accuracy and method comparison of the established method were evaluated.A total of 100 clinical serum specimens were collected from pregnant women in the Ningbo Yinzhou Hospital of Traditional Chinese Medicine from February to August 2022.The established CLIA was used for detection,and the results were compared with the results of Roche electrochemiluminescence assay.Results The optimal concentrations of biotinylated antibody and acridinium ester labeled antibody in the reagent were ultimately determined to be 2 μ g/ml and 100 ng/ml,respectively.The limit of blank of this method was 1.67 pg/ml,the coefficient of variation(CV)of precision within and between batches was lower than 5％,and the linear range was 8.9～81 206pg/ml.When the concentrations of serum hemoglobin,bilirubin,fat emulsion and biotin were lower than 500 mg/dl,20 mg/dl,1 450 FTU and 50 μ g/L,respectively,there would be no significant interference with the detected results.The recovery rate of the method was 98％.The correlation coefficient(r2)between the established method and Roche electrochemiluminescence assay was 0.995 3.The difference between the two group was significant(P=0.000 3).Conclusion The established method have good preliminary performance and can be further applied to the auxiliary screening of preeclampsia.

The current situation of tumor radiotherapy teaching is far behind the development of radiotherapy technologies. The construction of a teaching system based on an artificial intelligence-powered automatic target delineation system and a standardized cancer radiotherapy case library is operable and practical for realizing the standardization and homogenization of clinical target volume delineation teaching, improving students' precision and speed of target volume delineation, and promoting students' learning interest, initiative, and efficiency, which can bring new vitality to the development of radiotherapy education and is worthy of further exploration and promotion.