OBJECTIVE To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification. METHODS From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR. RESULTS Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis. CONCLUSION This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective To investigate the effect of N6-methyladenosine (m⁶A) reading protein human antigen R (HuR) on the migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1 (PFK1). Methods The tissue samples of 33 patients who were first diagnosed as colorectal cancer in Zhengzhou Central Hospital Affiliated to Zhengzhou University from April to December 2022 were collected. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of HuR and PFK1 mRNA in colorectal cancer tissues and adjacent tissues. The expression of HuR mRNA in normal intestinal epithelial cells NCM460 and colorectal cancer cells HCT8, SW480, SW620, HCT116, LoVo, RKO and COLO205 was detected. Small interfering RNA (siRNA) was used to construct a HuR knockdown colorectal cancer cell model. The effects of HuR on the migration and invasion of colorectal cancer cells were detected by cell scratch assay and Transwell assay. The expression of PFK1 mRNA and protein was detected by qRT-PCR and Western blot. Glucose intake and pyruvate production were detected by glucose content kit and pyruvate content kit, respectively. The relationship between HuR and PFK1 was analyzed by bioinformatics analysis, and the effect of HuR on the stability of PFK1 mRNA was evaluated by actinomycin D assay. Results In colorectal cancer tissues, HuR and PFK1 were highly expressed at mRNA level; HuR was highly expressed at mRNA level in colorectal cancer cell lines. Down-regulation of HuR significantly inhibited the migration and invasion of colorectal cancer cells, as well as glucose consumption and pyruvate production. Knockdown of HuR could reduce the stability of PFK1 mRNA and its expression at mRNA and protein levels. There were m⁶A modification sites on PFK1. Conclusion The m⁶A reading protein HuR may regulate the migration, invasion and glycolysis of colorectal cancer cells by recognizing the m⁶A site on PFK1 and reducing the stability of PFK1 mRNA.

Objective To compare the effectiveness of Defocus Incorporated Multiple Segments (DIMS) and High Aspheric Lenslet (HAL) defocus lenses in controlling myopia. Methods A total of 214 children and adolescents who were fitted with defocus lenses (DIMS or HAL) in our hospital from January to June 2023 were selected, including 100 cases in DIMS group and 114 cases in the HAL group. Changes in parameters such as spherical lens power, cylindrical lens power, spherical equivalent (SE), corneal curvature (K), axial length (AL), binocular accommodative response (BCC), positive/negative relative accommodation (PRA/NRA), distance/near latent phoria (DLP/NLP), and accommodative convergence to accommodation ratio (AC/A) were compared between the two groups before wearing and after wearing the lenses for 6 months, and the effectiveness of myopia control between DIMS and HAL was further compared. Results After wearing the lenses (DIMS or HAL) for 6 months, the average increase in axial length was (0.09±0.14) mm, the average increase in spherical lens power was (-0.11±0.23) D, the average increase in astigmatism was (-0.07±0.16) DC, and the average increase in spherical equivalent was (-0.15±0.24) D, with statistically significant differences observed for all these changes (t=9.24, -7.27, -6.60, -9.03, respectively, P < 0.001). Compared with parameters before wearing the lenses, statistically significant differences were noted after wearing for 6 months in spherical lens power, cylindrical lens power, SE, BCC, PRA, DLP, average K, and AL (P≤0.001), except for NRA (t=-0.12, P>0.05), NLP (t=-0.28, P>0.05), and AC/A (t=0.33, P>0.05). The differences in parameters between the two groups after wearing the lenses for 6 months showed a statistically significant difference only in the AL difference (t=4.38, P≤0.001), with no statistically significant differences observed for other parameter differences (P>0.05). Conclusion Wearing defocus lenses has a positive effect on controlling myopia, delaying axial length elongation, and maintaining binocular visual function balance.

Based on the virtual simulation of "digital embryo" in the digital teaching platform for medical morphology, this study constructs the course resources of human embryology by integrating the contents of the course, recording micro-videos, formulating course guides, and analyzing clinical cases, then implements the blended teaching model of pre-class preview, in-class discussion, and after-class expansion, and establishes a course evaluation system combining formative assessment and end-of-course assessment. Comparison of assessment scores and satisfaction questionnaire between traditional off-line teaching and blended teaching showed a significant improvement in total score, and more than 5% of the students reported a significant reduction in the difficulty of the course, while the degree of satisfaction with the course was increased by 11%. This suggests that the establishment of the blended teaching model of human embryology meets the requirements for personalized and diversified learning among students, realizes the diversity of teaching methods and teaching evaluation, and improves the quality of teaching.

Objective:To establish and preliminarily validate a nomogram model for predicting the risk of retinal vein occlusion (RVO).Methods:A retrospective clinical study. A total of 162 patients with RVO (RVO group) diagnosed by ophthalmology examination in The Second Affiliated Hospital of Xi'an Jiaotong University from January 2017 to April 2022 and 162 patients with age-related cataract (nRVO group) were selected as the modeling set. A total of 45 patients with branch RVO, 45 patients with central RVO and 45 patients with age-related cataract admitted to Xi'an Fourth Hospital from January 2022 to February 2023 were used as the validation set. There was no significant difference in gender composition ratio ( χ2=2.433) and age ( Z=1.006) between RVO group and nRVO group ( P=0.120, 0.320). Age, gender, blood routine (white blood cell count, hemoglobin concentration, platelet count, neutrophil count, monocyte count, lymphocyte count, erythrocyte volume, mean platelet volume, platelet volume distribution width), and four items of thrombin (prothrombin time, activated partial thrombin time, fibrinogen, and thrombin time) were collected in detail ), uric acid, blood lipids (total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, lipoprotein a), hypertension, diabetes mellitus, coronary heart disease, and cerebral infarction. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were calculated. The single logistic regression was used to analyze the clinical parameters of the two groups of patients in the modeling set, and the stepwise regression method was used to screen the variables, and the column graph for predicting the risk of RVO was constructed. The Bootstrap method was used to repeated sample 1 000 times for internal and external verification. The H-L goodness-of-fit test and receiver operating characteristic (ROC) curve were used to evaluate the calibration and discrimination of the nomogram model. Results:After univariate logistic regression and stepwise regression analysis, high density lipoprotein, neutrophil count and hypertension were included in the final prediction model to construct the nomogram. The χ2 values of the H-L goodness-of-fit test of the modeling set and the validation set were 0.711 and 4.230, respectively, and the P values were 0.701 and 0.121, respectively, indicating that the nomogram model had good prediction accuracy. The area under the ROC curve of the nomogram model for predicting the occurrence of post-stroke depression in the modeling set and the verification set was 0.741 [95% confidence interval ( CI) 0.688-0.795] and 0.741 (95% CI 0.646-0.836), suggesting that the nomogram model had a good discrimination. Conclusions:Low high density lipoprotein level, high neutrophil count and hypertension are independent risk factors for RVO. The nomogram model established based on the above risk factors can effectively assess and quantify the risk of post-stroke depression in patients with cerebral infarction.

Objective To observe the dynamic changes of cardiac lymphangiogenesis in Doxorubicin(DOX)-induced dilated cardiomyopathy(DCM)model mice,and to study the the protective mechanism of Kuoxin Decoction.Methods The DCM mouse model was established by intraperitoneal injection of DOX,and the dynamic observation was performed every week.On this basis,60 C57BL/6 mice were randomly divided into 6 groups(n=10):control group,Model group,L-KXD,M-KXD and H-KXD groups and Captopril group.After successful modeling,the KXD and the positive control drug Captopril were administered continuously for 28 days.Echocardiography was used to detect cardiac function in mice,HE staining and Masson staining were used to observe pathological and morphological changes of the heart,Whole-mount immunofluorescent staining was used to detect the expression of LYVE-1 and Podoplanin in epicardial lymphatic vessels,Western blot was used to detect the expression of VEGFR-3 protein,and qPCR was used to detect the expression of VEGFR-3 mRNA.Results DCM mice induced by DOX showed significant cardiac function decline from the third week(DOX:15 mg·kg-1,P<0.05),and significant ventricular remodeling at the fifth week(DOX:15 mg·kg-1,P<0.01);The lymphatic vessel area of the mouse heart decreased significantly from the fourth week(DOX:20 mg·kg-1,P<0.0001),and the expression of VEGFR-3 decreased significantly from the third week(DOX:15 mg·kg-1,P<0.01).Conclusion KXD can improve ventricular remodeling and cardiac function in DOX-induced DCM mice,promote cardiac lymphangiogenesis,and upregulate the expression of VEGFR-3 at protein and mRNA levels,with a better effect than captopril.DOX-induced cardiac lymphangiogenesis in DCM mice leads to severe myocardial fibrosis and weakened cardiac function,which gradually worsens with the accumulation of modeling time and dose.KXD can promote cardiac lymphangiogenesis and improve cardiac function in DOX-induced DCM mice.The mechanism may be related to the up-regulation of VEGFR-3 expression.

Objective: To investigate the trends in incidence of viral hepatitis in Yuxi City, Yunnan Province from 2004 to 2022, so as to provide insights into the management of viral hepatitis. Methods: Data of viral hepatitis cases in Yuxi City from 2004 to 2022 were retrieved from the China Disease Prevention and Control Information System. The temporal, human and spatial distribution of viral hepatitis cases were analyzed using a descriptive epidemiological method, and the trends in incidence of viral hepatitis were evaluated in Yuxi City from 2004 to 2022 using annual percent change (APC) and average APC (AAPC). Results: A total of 37 430 viral hepatitis cases were reported in Yuxi City from 2004 to 2022, with an average annual incidence rate of 91.27/105, and the incidence showed a tendency towards a rise (AAPC=12.686, P<0.05). There were 29 229 cases with hepatitis B, 5 796 cases with hepatitis C, 1 451 cases with hepatitis A, 520 cases with hepatitis E and 434 cases with unclassified hepatitis reported in Yuxi City, with average annual incidence rates of 71.27/105, 14.13/105, 3.54/105, 1.27/105 and 1.06/105, respectively. The average annual incidence rates of viral hepatitis were 98.24/105 and 78.94/105 among men and women, which both appeared a tendency towards a rise (AAPC=12.415% and 12.581%, both P<0.05). The highest average annual incidence of viral hepatitis was seen among residents at age of 25 to 29 years (139.89/105), with the lowest seen among residents at ages of 0 to 4 years (11.38/105), and the average annual incidence of viral hepatitis appeared a tendency towards a rise with age (P<0.05). The highest average annual incidence of viral hepatitis was seen in Huaning County (234.24/105), with the lowest seen in Chengjiang City (26.11/105), and the average annual incidence appeared a tendency towards a rise in Xinping County from 2004 to 2022 (AAPC=21.451%, P<0.05). Conclusions The reported incidence of viral hepatitis appeared a tendency towards a rise in Yuxi City from 2004 to 2022, with hepatitis B as the main type. High incidence was seen among men and adolescents. The viral hepatitis control strategy requires to be adjusted with adaptations to high-incidence hepatitis subgroups, residents and regions.