With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Objective: To construct a nonsuicidal selfinjury (NSSI) risk prediction model for middle school students using different machine learning algorithms and evaluate the models effectiveness, so as to provide guidance for the prevention and control of NSSI in campus. Methods: In March 2023, a total of 3 372 middle and high school students from schools in Nanchang, Fuzhou and Shangrao cities in Jiangxi Province were selected by combining stratified random cluster sampling and convenient sampling methods. Questionnaire surveys were conducted using various instruments including general information questionnaire, Selfesteem Scale, Ottawa Selfinjury Scale, Social Support Assessment Scale, Chinese Version of the Olweus Bullying Questionnaire, Event Attribution Style Scale, Adolescent Resilience Scale, and Adolescent Life Events Scale. Data were divided into training set (n=2 361) and test set (n=1 011) at a ratio of 7∶3, and variables were selected based on univariate and LASSO regression results. Four machine learning algorithms including namely random forest, support vector machine, Logistic regression and XGBoost, were used to construct NSSI risk prediction models, and the models performance was evaluated and compared using metrics including area under curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value and F1 score. Results: The detection rate of NSSI among middle school students was 34.4%. Univariate analysis showed that there were statistically significant differences in NSSI detection rates among middle school students of different grades, genders, registered residence locations, whether they were class cadres and four types of bullying (physical, verbal, relational bullying and cyberbullying) (χ2=27.17, 15.81, 11.54, 4.63；68.22, 140.63, 77.81, 13.95, P<0.05). NSSI was included as the dependent variable in the LASSO regression model for variable screening, and the results regression identified 10 predictive variables including grade level, selfesteem, subjective support, support utilization, verbal bullying, emotional control, interpersonal relationships, punishment, loss of relatives and property, and health and adaptation issues. The AUC values of random forest, support vector machine, Logistic regression, and XGBoost algorithms were 0.76, 0.76, 0.76 and 0.77, respectively, with no statistically significant differences between pairwise comparisons (Z=-0.59-0.82, P>0.05). Sensitivity values were 0.62, 0.61, 0.62 and 0.61, respectively. Specificity values were 0.74, 0.78, 0.78 and 0.78, respectively. Positive predictive values were 0.56, 0.59, 0.60 and 0.59, respectively. Negative predictive values were 0.79, 0.79, 0.80 and 0.79, respectively. F1 scores were 0.59, 0.60, 0.61 and 0.60, respectively. Conclusions All four nonsuicidal selfinjury risk prediction models perform well, with the Logistic regression model slightly outperforming the others. Schools and parents should pay attention to the predictive factors corresponding to NSSI, so as to reduce the occurrence of NSSI among middle school students.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.
Animals ; Cytokines/metabolism* ; Dendrobium ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology* ; Dysbiosis/drug therapy* ; Gastrointestinal Microbiome ; Inflammation/drug therapy* ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Phosphatidylinositol 3-Kinases ; Pneumonia ; Rhinitis, Allergic/metabolism*

Objective: To investigate the impact of type 2 diabetes mellitus on progression and revascularization of coronary non-target lesions in patients with coronary heart disease. Methods: From January 2010 to September 2014, we retrospectively analyzed the clinical data of patients with coronary heart disease who underwent two consecutive coronary angiographies at Fuwai Hospital. At least one coronary non-target lesion was recorded at the first procedure in these patients. Patients were grouped according to the diagnose of type 2 diabetes mellitus. Demographic features, risk factors of coronary heart disease, laboratory results as well as characteristics of coronary non-target lesions were collected at baseline (first coronary angiography) and follow-up (second coronary angiography). Lesion progression was defined by quantitative coronary angiography analysis. Lesions revascularization was recorded. Multivariable Cox regression analysis was used to define the impacts of diabetes mellitus on progression and revascularization of non-target lesions. Subgroup analysis in diabetic and non-diabetic groups were further performed. Receiver operating characteristics curve was used to identify the predictive value of HbA1c. Results: A total of 1 255 patients were included, and 1 003(79.9%) were male, age was(58.0±9.7) years old. And 486 patients were diagnosed with type 2 diabetes mellitus. Follow-up time was (14.8±4.5) months. Compared with non-diabetic group, diabetic group were older with less male and had higher BMI index as well as higher prevalence of hypertension, dyslipidemia, prior myocardial infarction and prior percutaneous coronary intervention(all P<0.05). Diabetic patients also had higher level of white blood cells, erythrocyte sedimentation rate, C-reactive protein, endothelin and HbA1c at both baseline and follow-up compared with non-diabetic patients (all P<0.01). There was no significant difference on progression of non-target lesions (20.0%(97/486) vs. 18.5%(142/769), P=0.512), revascularization of non-target lesions (13.2%(64/486) vs. 15.9%(122/769), P=0.190) and non-target lesion related myocardial infarction(1.9%(9/486) vs. 1.3%(10/769), P=0.436) between diabetic and non-diabetic patients. Multivariable Cox regression analysis revealed that diabetes mellitus was not an independent predictor for progression and revascularization of non-target lesions (Both P>0.05). Subgroup analysis in diabetic patients showed that baseline HbA1c level(HR=1.160, 95%CI 1.009-1.333, P=0.037) was an independent predictor for non-target lesion progression. Cut-off value of HbA1c was 6.5% (Area Under Curve(AUC) 0.57, specificity 88.7%; sensitivity 24.2%, P=0.046) by receiver operating characteristics curve. Patients with HbA1c level above 6.5% had 2.8 times higher risk of lesion progression compared with patients with HbA1c level below 6.5% (HR=2.838, 95%CI 1.505-5.349, P=0.001). Compared with non-diabetic patients, diabetic patients with HbA1c below 6.5% also had lower risk of lesion progression (HR=0.469, 95%CI 0.252-0.872, P=0.012). ST-segment elevated myocardial infarction was an independent predictor for revascularization of non-target lesions in diabetic patients. Conclusion: Type 2 diabetes mellitus is not an independent predictor for progression and revascularization of coronary non-target lesions in patients with coronary heart disease. However, elevated HbA1c level is a risk factor for progression of non-target lesion in patients with type 2 diabetes mellitus.
Aged ; Coronary Angiography ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Retrospective Studies ; Risk Factors ; Treatment Outcome

Objective To study the influence of targeted silencing of DEK on the proliferation and cell cycle of human hepatoma cell lines.Methods The human hepatoma cells line HepG2 were routinely cuhured and the cells were divided into blank control group,siRNA control group and DEK siRNA group when the cells grew to 90％ tusion.The cells in blank control group were cultured normally without any treatment;the cells in siRNA control group and DEK siRNA group were transfected with siRNA expression vector and DEK siRNA expression vector mediated by LipofectamineTM2000 liposomes,respectively.The expression of DEK mRNA in HepG2 cells was detected by real-time polymerase chain reaction;the expression of DEK and CyclinD1 protein in HepG2 cells was detected by Western blot;the proliferation of HepG2 cells was detected by methyl thiazolyl tetrazolium method,and the cell cycle was observed by flow cytometry.Results The expression of DEK mRNA in the blank control group,siRNA control group and DEK siRNA group was 0.826 ±0.052,0.776 ±0.051 and 0.420 ±0.050 respectively;the expression of DEK protein in the blank control group,siRNA control group and DEK siRNA group was 0.691 ± 0.073,0.726±0.061 and 0.311 ±0.038 respectively;the expression of CyclinDl protein in the blank control group,siRNA cuntrol group and DEK siRNA group was 0.712 ± 0.069,0.780 ± 0.074 and 0.434 ± 0.039 respectively.The expressions of DEK mRNA,DEK protein and CyclinD1 protein in DEK siRNA group were significantly lower than those in the blank control group and siRNA control group (P ＜ 0.05);there was no statistic difference in the expression of DEK mRNA,DEK protein and CyclinD1 protein between the blank control group and siRNA control group(P ＜0.05).The proliferation ability of HepG2 cells in DEK siRNA group after transfection of 24,48,72,96,120 h was significantly lower than that in the blank control group and siRNA control group(P ＜0.05);there was no statistic difference in the proliferation ability of HepG2 cells between the blank control group and siRNA control group at each time point(P ＜ 0.05).The proportion of G0 + G1 phase cells in DEK siRNA group was significantly higher than that in the blank control group and siRNA control group(P ＜ 0.05);the proportions of S phase and G2 + M phase cells in DEK siRNA group were significantly lower than those in the blank control group and siRNA control group(P ＜ 0.05);there was no statistic difference in the proportion of G0 + G1 phase,S phase and G2 + M phase cells between the blank control group and siRNA control group (P ＜ 0.05).The result of Pearson correlation analysis showed that the expression of CyclinD1 protein was positively correlated with the expression of DEK mRNA and protein(r =0.909,0.899;P ＜ 0.05).Conclusion DEK siRNA can inhibit the proliferation of HepG2 cells,and change the cell cycle distribution through down regulating the expression of DEK gene in HepG2 cells.This process may be related to the down regulation of the expression of CyclinD1.

MTT assay was used in this study to investigate the inhibitory effect of danshensu on the activity of 2.2.15 cells among human hepatoma cell line (HepG2); indirect fluorescence labeling method was used to measure the changes of reactive oxygen levels in the cells; ELISA method was used to determine hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels in cellular supernatants; HBV DNA level was measured with fluorogenic quantitative PCR method. The inhibitory effect of danshensu on HBV RT(hepatitis B virus reverse transcriptase) was studied by using enzyme inhibition dynamics, and the effect of danshensu on secondary structure of HBV reverse transcriptase was monitored by using circular dichroism. The results showed that danshensu had a good inhibitory effect on the growth of HepG2.2.15 cells, with a half inhibitory concentration (IC₅₀) of (15.35±2.43) μmol•L⁻¹; danshensu could significantly inhibit HBsAg and HBeAg expressions, and showed an inhibitory effect on HBV DNA replication. In addition, danshensu was an effective inhibitor for HBV reverse transcriptase [IC₅₀ (21.32±2.43) μmol•L⁻¹]. The fluorescence labeling results showed that the reactive oxygen levels in the cells were increased with the increase of danshensu concentration. Circular dichroism analysis showed that danshensu could induce partial change of conformation of HBV reverse transcriptase and gradually increased α-helical content. These results indicated that danshensu could make the structure of the enzyme become closer by binding to HBV reverse transcriptase, which was not conducive to the formation of the active center, so it could finally decrease the activity of HBV reverse transcriptase. Such decrease in enzyme activity would directly affect the HBV DNA replication, and combined with the decrease of the antigen levels, the effect of danshensu on HBV was increased.

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors

OBJECTIVETo evaluate the impact of nicotine- and tar-free cigarette smoke extract (fCSE) on the serum testosterone (T) level and erectile function of male rats.

METHODSWe randomized 30 male SD rats to three groups of equal number to receive subcutaneous injection of PBS (1.0 ml / 300 g body weight per day), fCSE (1.0 ml/300 g body weight per day), and reduced glutathione hormone (GSH, 200 mg per kg body weight per day) in addition to fCSE (fCSE + GSH), respectively, all for 8 weeks. Then we evaluated the erectile function of the rats by measuring the maximal intracavernous pressure (MICP), mean arterial pressure (MAP), ICP/MAP ratio, time of stimulation to MICP (Tmax), and cavernosal filling fate (CFR). We determined the serum T level, the activities of superoxide dismutase (SOD) , malondialdehyde (MDA), and nitric oxide synthase (NOS) in the cavernosal tissue, and also observed the morphological changes of the corpus cavernosum.

RESULTSCompared with the controls, the rats of the fCSE group showed obvious decreases in the levels of serum T ([5.37 ± 1.43] vs [3.22 ± 1.11] μg/L), NOS ([2.90 ± 0.27] vs [1.67 ± 0.18] U/mg) , and SOD ([18.41 ± 1.09] vs [13.36 ± 1.18] U/mg prot) and erectile function-related indexes MICP ([85.92 ± 6.36] vs [58.99 ± 10.76] mmHg), MICP/MAP (0.86 ± 0.09 vs [0.56 ± 0.08]), and CFR (2.14 ± 0.44 vs 0.89 ± 0.44), but markedly increased Tmax ([29.90 ± 5.78] vs [42.90 ± 8.56]s), with a positive correlation between the serum T level and CFR (r = 0. 364, P < 0.05). Masson staining revealed a lower ratio of the corpus cavernosum smooth muscle tissue to collagen fiber in the fCSE group (0.27 ± 0.04) than in the control (0.98 ± 0.12). Compared with the fCSE group, the fCSE + GSH group exhibited significantly improved MICP ([58.99 ± 10.76 ] vs [77.95 ± 7.71] mmHg), MICP/MAP (0.56 ± 0.08 vs 0.77 ± 0.09), and CFR (0.89 ± 0.44] vs 1.76 ± 0.42) and shortened Tmax ([42.90 ± 8.56 ] vs [32.10 ± 5.84 ] s). The ratio of the corpus cavernosum smooth muscle tissue to collagen fiber was higher in the fCSE + GSH than in the fCSE group (0.77 ± 0.09 vs 0.27 ± 0.04) but still lower than in the control (0.98 ± 0.12).

CONCLUSIONNicotine- and tar-free cigarette smoke extract reduces the serum T level and erectile function of rats, which is related to oxidative stress. Antioxidant therapy can improve erectile function but has a limited value for morphological protection of the penile tissue.

Animals ; Erectile Dysfunction ; chemically induced ; Male ; Malondialdehyde ; metabolism ; Muscle, Smooth ; pathology ; Nicotine ; Nitric Oxide Synthase ; metabolism ; Penile Erection ; drug effects ; Penis ; pathology ; Rats ; Rats, Sprague-Dawley ; Smoke ; adverse effects ; Superoxide Dismutase ; metabolism ; Tars ; Tobacco ; adverse effects