The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

To investigate the risk factors for early relapse after curative resection of Siewert type Ⅱ/Ⅲ adenocarcinoma of esophagogastric junction (AEG) and construct a visual predictive model.

Methods:A total of 392 patients with seasonal allergic rhinitis were selected from the population of the epidemiological investigation project of allergic diseases in Hohhot, Inner Mongolia. The project was led by Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, and assisted by Hohhot First Hospital from April to May 2023. The patients were randomly divided into a spleen aminopeptide group (296 cases) and control group (96 cases) at a ratio of 3∶1, and the enrollment period was from June 1 to 14, 2023. The treatment group was treated with spleen aminopeptide oral solution for 12 weeks starting from 4-6 weeks (±7 days) before the pollen dispersal period, while the control group was treated with a simulated agent of spleen aminopeptide oral solution. Both the treatment group and the control group were treated with oral antihistamines and/or nasal glucocorticoids as needed during the pollen dispersal period. Evaluate the therapeutic effect by comparing the symptom scores, drug scores and quality of life scores of the two groups, and detect the expression levels of cytokines in serum. Symptom scores, quality of life scores, drug scores and laboratory results were compared by independent sample t test/Kruskal-Wallis test and χ2 test/Fisher′s exact test. Results:Compared with the control group, spleen aminopeptide treatment for 12 weeks significantly improved symptoms of nasal congestion [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=6.308, P<0.05], nasal itching [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=4.966, P<0.05], sneezing [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=5.245, P<0.05], runny nose [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=5.41, P<0.05] and tearing [ M( Q1, Q3):1(0, 2) vs. 1(0, 3), H=4.664, P<0.05]. At 12 weeks of treatment, the scores of nasal symptoms and ocular symptoms in control group and experimental group were significantly increased compared with baseline ( P<0.05). In experimental group, nasal congestion [ M( Q1, Q3):1(0, 1) vs. 1(0, 2), H=4.042, P<0.05], eye itching/foreign body sensation/redness symptom scores [ M( Q1, Q3):1(0, 2) vs. 1(0, 2), H=5.302, P<0.05] and total scores [ M( Q1, Q3):4(-1, 9) vs. 5(0, 12.5), H=3.958, P<0.05] were significantly increased. The antihistamine drug score of the splenic peptide treatment group at 6 weeks were lower than that of the control group ( H=4.232, P<0.05). After 12 weeks of treatment, the antihistamine drug score [ M( Q1, Q3):10(0, 24) vs. 19(2, 36.5), H=6.67, P<0.05] and the total drug score [ M( Q1, Q3):28.5(5, 77.5) vs. 46(6, 155.5), H=3.995, P<0.05] were significantly lower than those of the control group. The serum IL-17A levels of the treatment group were significantly lower than those of the control group after 6 weeks (0.7±1.77 vs. 0.85±1.67 ,H=10.08, P<0.05) and 12 weeks (0.81±1.63 vs. 0.94±1.73, H=5.196, P<0.05) of splenic aminopeptide treatment. Conclusions:Early treatment with spleen aminopeptide oral solution can significantly improve nasal and ocular symptoms of patients with seasonal allergic rhinitis, reduce the use of drugs during the onset period, and improve the quality of life. It may exert an immunomodulatory effect by reducing the expression level of IL-17A in the serum of patients.Objects:To conduct a study on the prevention and treatment of seasonal allergic rhinitis in Hohhot, Inner Mongolia, evaluate the preventive and therapeutic effects of spleen aminopeptide oral solution on seasonal allergic rhinitis, and explore its related mechanisms.

Methods:A total of 392 patients with seasonal allergic rhinitis were selected from the population of the epidemiological investigation project of allergic diseases in Hohhot, Inner Mongolia. The project was led by Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, and assisted by Hohhot First Hospital from April to May 2023. The patients were randomly divided into a spleen aminopeptide group (296 cases) and control group (96 cases) at a ratio of 3∶1, and the enrollment period was from June 1 to 14, 2023. The treatment group was treated with spleen aminopeptide oral solution for 12 weeks starting from 4-6 weeks (±7 days) before the pollen dispersal period, while the control group was treated with a simulated agent of spleen aminopeptide oral solution. Both the treatment group and the control group were treated with oral antihistamines and/or nasal glucocorticoids as needed during the pollen dispersal period. Evaluate the therapeutic effect by comparing the symptom scores, drug scores and quality of life scores of the two groups, and detect the expression levels of cytokines in serum. Symptom scores, quality of life scores, drug scores and laboratory results were compared by independent sample t test/Kruskal-Wallis test and χ2 test/Fisher′s exact test. Results:Compared with the control group, spleen aminopeptide treatment for 12 weeks significantly improved symptoms of nasal congestion [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=6.308, P<0.05], nasal itching [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=4.966, P<0.05], sneezing [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=5.245, P<0.05], runny nose [ M( Q1, Q3):2(1, 2) vs. 2(1, 3), H=5.41, P<0.05] and tearing [ M( Q1, Q3):1(0, 2) vs. 1(0, 3), H=4.664, P<0.05]. At 12 weeks of treatment, the scores of nasal symptoms and ocular symptoms in control group and experimental group were significantly increased compared with baseline ( P<0.05). In experimental group, nasal congestion [ M( Q1, Q3):1(0, 1) vs. 1(0, 2), H=4.042, P<0.05], eye itching/foreign body sensation/redness symptom scores [ M( Q1, Q3):1(0, 2) vs. 1(0, 2), H=5.302, P<0.05] and total scores [ M( Q1, Q3):4(-1, 9) vs. 5(0, 12.5), H=3.958, P<0.05] were significantly increased. The antihistamine drug score of the splenic peptide treatment group at 6 weeks were lower than that of the control group ( H=4.232, P<0.05). After 12 weeks of treatment, the antihistamine drug score [ M( Q1, Q3):10(0, 24) vs. 19(2, 36.5), H=6.67, P<0.05] and the total drug score [ M( Q1, Q3):28.5(5, 77.5) vs. 46(6, 155.5), H=3.995, P<0.05] were significantly lower than those of the control group. The serum IL-17A levels of the treatment group were significantly lower than those of the control group after 6 weeks (0.7±1.77 vs. 0.85±1.67 ,H=10.08, P<0.05) and 12 weeks (0.81±1.63 vs. 0.94±1.73, H=5.196, P<0.05) of splenic aminopeptide treatment. Conclusions:Early treatment with spleen aminopeptide oral solution can significantly improve nasal and ocular symptoms of patients with seasonal allergic rhinitis, reduce the use of drugs during the onset period, and improve the quality of life. It may exert an immunomodulatory effect by reducing the expression level of IL-17A in the serum of patients.Objects:To conduct a study on the prevention and treatment of seasonal allergic rhinitis in Hohhot, Inner Mongolia, evaluate the preventive and therapeutic effects of spleen aminopeptide oral solution on seasonal allergic rhinitis, and explore its related mechanisms.

Objective To establish a prediction model for in-hospital mortality risk in patients with sepsis-induced coagulopathy based on LASSO regression.Methods Patients with sepsis-induced coagulopathy ad-mitted to intensive care unit(ICU)at Beth Israel Deaconess Medical Center during 2008 to 2019 were selected from the Medical Information Market for Intensive Care(MIMIC)-Ⅳ database(version 2.1)for retrospective study.The study subjects were randomly divided into modeling group and verification group,and the feature variables were screened by LASSO regression.The feature variables were analyzed by multivariate Logistic re-gression to determine independent risk factors,and the nomogram prediction model was established at the same time.The model performance was evaluated by drawing calibration curve and receiver operating charac-teristic(ROC)curve,as well as decision curve analysis.Results A total of 4 994 patients with sepsis-induced coagulopathy admitted to ICU for the first time were enrolled in this study.They were randomly divided into a model group(n=3 495)and a validation group(n=1 499)at a ratio of 7:3.Multivariate Logistic regres-sion analysis showed that age,mean respiratory rate,mean corpuscular hemoglobin concentration,red blood cell count,platelet count,prothrombin time,anion gap,acute physiological score Ⅲ and acute kidney injury were independent risk factors for in-hospital mortality of patients with sepsis-induced coagulopathy.Based on the above independent risk factors,a nomographic prediction model was constructed.The area under the ROC curve and 95％confidence interval of the nomogram in the modeling group and validation group were 0.864(0.849-0.880)and 0.877(0.852-0.901),respectively.The sensitivity was 0.795 and 0.763,and the speci-ficity was 0.779 and 0.843,respectively.The calibration curve suggested that the predicted probability was ba-sically consistent with the actual probability,and the decision curve analysis showed that it had good clinical net benefits within a wide range of threshold.Conclusion The nomogram model based on MIMIC-Ⅳ database has good predictive value for predicting the in-hospital mortality of patients with sepsis-induced coagulopathy and can be used to guide clinical work.

Objective To establish and evaluate a rapid detection method for SARS-CoV-2 based on reverse transcriptase-recombinase aided amplification(RT-RAA)combined with the clustered regularly interspaced short palindromic repeats(CRISPR)/Cas12a system.Methods RT-RAA primers and CRISPR-derived RNA(crRNA)were designed based on the nucleocapsid(N)gene of SARS-CoV-2 from NCBI database.The detection system was optimized with magnesium acetate(MgAc)concentration,RT-RAA reaction tempera-ture and time and LbCas12a reaction temperature.The sensitivity and specificity of the method were evaluated using recombinant plas-mids(100-106 copies/μL)and other respiratory pathogens.The RT-RAA-CRISPR/Cas12a method was compared with RT-PCR by tes-ting 70 clinical samples in parallel.Results The optimized RT-RAA-CRISPR/Cas12a assay could detect SARS-CoV-2 within 50 min at 37 ℃.The limit of detection was 10 copies/μL for the fluorescence-based method and 1×102 copies/μL for the lateral flow assay.The method specifically detected SARS-CoV-2 without cross-reactivity to other respiratory pathogens.The results of testing 70 clinical samples using RT-RAA-CRISPR/Cas12a showed agreement of 100％with those of RT-PCR.Conclusion The established RT-RAA-CRISPR/Cas12a assay for SARS-CoV-2 detection is rapid,cost-effective,highly sensitive and specific.It can be performed by less experienced personnel and no expensive equipment is required,thus it may provide a new approach for rapid clinical diagnosis and large-scale on-site screening of SARS-CoV-2.

Objectives:To search, evaluate, and summarize the evidence related to the application management of over-the-counter (OTC) medications for constipation in the elderly, providing evidence-based support for the rational use of these medications.Methods:A systematic search was conducted through computerized decision support systems, guideline websites, professional association websites, and databases for clinical decisions, guidelines, evidence summaries, and expert consensus on the management of OTC medications for constipation in the elderly. The search period spanned from January 2018 to March 2023. The quality of the literature was independently assessed, and evidence was extracted. The 2014 version of the Joanna Briggs Institute (JBI) evidence grading system was used to determine the levels of evidence.Results:A total of 18 article were included, consisting of two clinical decisions, five guidelines, seven expert consensus statements, and four evidence summaries. These covered five areas: medication principles for elderly individuals with different characteristics, medication selection, medication monitoring, health education, and precautions, culminating in a total of 30 best evidence.Conclusions:This study summarizes the best evidence for the management of OTC medications for constipation in the elderly, providing evidence-based support for the rational application of these medications.

Objective To investigate whether an association existed between elevated serum β2-microglobulin levels and post stroke cognitive impairment(PSCI).Methods A total of 140 patients with ischemic stroke in Wenzhou People's Hospital during December 2022 to December 2023 were prospectively were enrolled including 73 patients in the PSCI group and 67 patients in the non-post stroke cognitive impairment(PSNCI)group.Serum β2-microglobulin and other biochemical indicators were measured within 24 hours after admission.PSCI was assessed using the mini-mental state examination(MMSE)score with a threshold of≥27 points serving as the diagnostic criterion.Results The age,National Institutes of Health Stroke Scale(NIHSS)score at admission,proportion of low education level,proportion of multiple or large area infarction and serum β2-microglobulin level in the PSCI group were higher than those in the PSNCI group.Multivariate Logistic regression analysis showed that age,NIHSS score at admission,multiple or large area infarction and serum β2-microglobulin level were risk factors for PSCI,and education level was a protective factor for PSCI.Conclusion The increase of β2-microglobulin level is a risk factor for cognitive impairment after ischemic stroke.The detection of β2-microglobulin level in stroke patients may realize the early detection of PSCI.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.