Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

ObjectiveTo reveal the effects of overexpression and knockdown of CDH18 gene on cervical cancer proliferation and migration levels through the Wnt/β-catenin signaling pathway in cervical cancer cells. MethodsA comprehensive analysis of CDH18-interacting molecules was performed via the bioinformatics STRING database （http：//cn.string-db.org）. Molecular docking between Wnt/β-catenin inhibitor XAV939 and β-catenin was performed using the bioinformatics tool AutoDock （http：//autodock.scripps.edu）. The effect of CDH18 on β-catenin subcellular distribution was detected by laser confocal microscopy. EdU assay， wound healing assay and Transwell assay were used to detect the effects of CDH18 gene overexpression， CDH18 gene knockdown and the XAV939 on cell proliferation and migration. Western blot was performed to measure the expression levels of Wnt/β-catenin pathway-related molecules， including β-catenin， transcription factor 4 （TCF4）， and cellular myelocytomatosis oncogene （c-Myc）， following CDH18 gene overexpression， CDH18 gene knockdown， or XAV939 treatment. ResultsIn SiHa and HeLa cells， CDH18 gene overexpression significantly increased the protein expression levels of β-catenin， TCF4 and c-Myc， decreased the protein expression of GSK-3β， and enhanced cell proliferation and migration， with statistically significant differences （P<0.05）. Conversely， CDH18 gene knockdown significantly reduced the protein expression of β-catenin， TCF4 and c-Myc， elevated GSK-3β expression， and suppressed cell proliferation and migration （P<0.05）.Treatment with XAV939 in SiHa and HeLa cells downregulated β-catenin， TCF4 and c-Myc， upregulated GSK-3β， and inhibited cell proliferation and migration， with significant differences （P<0.05）. ConclusionCDH18 promotes the proliferation and migration of cervical cancer cells via the Wnt/β-catenin signaling pathway.

Refinement and standardisation of the management of clinical diagnostic and treatment operations is a key aspect of achieving high-quality development in hospitals.By analysing the management status quo of clinical diagnosis and treatment operations in hospitals,it combed the problems existing in this field.Based on the closed-loop management model,it proposed measures and recommendations to promote the continuous optimisation of the management of clinical diagnostic operations in hospitals.Hospitals should establish hospital-level operation catalog and conduct classified management,authorize operators and dynamically adjust them,carry out operation quality management,pay attention to information management of operation management,and combine operation management with physician performance management.

Objective Investigate the expression level of discs large homolog associated protein 5(DLGAP5)in oral squamous cell carcinoma(OSCC)and analyze its effects on cell proliferation,migration,invasion capacity,and the Warburg effect.Methods Bioinformatics analysis was performed to identify the potential therapeutic targets for OSCC.A total of 72 OSCC tissue samples and 40 adjacent non-cancerous tissue samples collected in the First Affiliated Hospital of Shihezi University from 2013 to 2024 were included,and the clinical pathological and prognostic data were collected from patients.Immunohistochemistry assay was applied to detect the protein expression of DLGAP5,and its association with clinical pathological features was analyzed.Kaplan-Meier survival curve was plotted for survival analysis,and Cox regression model was employed to analyze the prognostic factors.The expression of DLGAP5 at mRNA and protein levels was detected in HOK,SCC-9,SCC-15,SCC-25,and CAL-27 cell lines with RT-qPCR and Western blotting,respectively.Four small interfering RNAs(siRNAs)were designed to target the DLGAP5 sequence,and then based on the transfection efficiency,the sequence with optimal silencing effect was selected for subsequent functional studies.After DLGAP5 was silenced in the CAL-27 and SCC-15 cells,Western blotting was applied to detect the expression of hexokinase 2(HK2)and enolase 1(ENO1),CCK-8,scratch healing and Transwell assays were conducted to assess cell proliferation,migration,and invasion capabilities,and glucose,lactate,and ATP detection kits were utilized to determine the glycolytic metabolic levels in OSCC cells.Results Bioinformatics analysis indicates that DLGAP5 is a potential key therapeutic target for OSCC.Experimental validation demonstrated that DLGAP5 was highly expressed in both OSCC tissues and cells(P<0.05).Analysis of clinical pathology and prognostic data revealed that DLGAP5 expression level was significantly correlated with tumor TNM stage,lymph node metastasis,and differentiation grade in OSCC patients,and high DLGAP5 expression was associated with poor prognosis(P<0.05).DLGAP5 silencing resulted in significantly reduced expression of HK2 and ENO1,markedly decreased levels of glycolytic metabolites(P<0.05),and notably declined cell proliferation,migration,and invasion capabilities(P<0.05).Conclusion DLGAP5 is highly expressed in OSCC.Silencing DLGAP5 may inhibit OSCC cell proliferation,migration,and invasion by indirectly regulating the Warburg effect,and the molecule is associated with poor prognosis in the OSCC patients.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Objective: To analyze the relationship between vitamin D and ferritin nutritional status with physical indicators in primary and secondary school students in the key nutrition monitoring counties of Xinjiang, so as to provide reference for early prevention and intervention of students nutrition issues. Methods: From November to December 2023, 1 071 students aged 6-18 from key nutrition monitoring counties in the Xinjiang Nutrition Improvement Plan area were selected via stratified random sampling for physical and biochemical tests. The U test and Kruskal-Wallis H-test were used to compare the differences in physical indicators and the distribution of vitamin D and ferritin levels. Chi-square test was used to compare the prevalence of vitamin D and ferritin deficiencies among different groups of primary and secondary school students. Pearson correlation was used to analyze the relationship between the nutritional levels of vitamin D and ferritin and physical indicators. Results: The median vitamin D level was 14.7 (10.7, 19.0)ng/mL, with deficiency and insufficiency rates of 30.8% and 37.4% among primary and secondary school students in the key nutrition monitoring counties of Xinjiang Nutrition Improvement Plan area. Ferritin levels were 57.4 (37.7, 83.9)μg/L, with a deficiency rate of 5.7%. Males, primary school students, and rural residents had higher vitamin D and ferritin levels than females, secondary school students, and urban residents ( U =-11.35, -6.88, -4.52; -3.94, -9.17, -5.23, P <0.05). Vitamin D deficiency was more prevalent in females, secondary school students, and urban students ( χ 2=97.52, 49.01, 21.89, P <0.05), while ferritin deficiency was higher in primary school students and urban areas ( χ 2=34.11, 5.63, P <0.05). Significant differences in body mass index (BMI) and waist circumstance (WC) were observed across vitamin D/ferritin statuses ( U/H =35.47, 22.82; -4.19 , -5.36, P <0.05). Vitamin D and ferritin levels negatively correlated with age, BMI, and WC but positively with waist-to-height ratio (WHtR) ( r = -0.31, -0.19, -0.19, 0.20; -0.32, -0.13, -0.21, 0.08, P <0.05). Conclusions Vitamin D and ferritin levels in primary and secondary school students in key nutritional monitoring counties in Xinjiang are correlated with age, BMI, WC and WHtR, and there are nutrient deficiencies. Targeted measures are recommended to improve nutritional status and physical health.