According to the results of activity-structure relationship (SAR) studies of alpha1-adrenoceptor antagonists hydantoin-phenylpiperazine and benzimidazo-arypiperazine derivatves, to design and synthesize a series of novel phenylpiperazine alpha1-adrenoceptor antagonists with more potent vasorelaxant activity, active metabolites of naftopidil were used as lead compounds. Ten novel R,S-1-substituted phenyl-4-[3-(naphthal-yl-oxy)-2-hydroxy propyl]-piperazine were designed and synthesized, their vasorelaxant activity was evaluated by calculating inhibition rate of phenylephrine-induced vasocontration of rabbit artery trips. Five compounds exhibited vasorelaxant activity, and compound 16 showed significant vasorelaxant activity in vitro. At 0.01 and 1 micromol x L(-1), its inhibition rates were 7.03% and 22.72%, respectively. This compound possessed ideal vasorelaxant activity in vitro, and would be selected for further anti-hypertension evaluation in vivo. Moreover, by analyzing the primary activity and structure relationship of these compounds, it could be concluded that the SAR results of the reported phenylpiperazine alpha1-adrenoceptor antagonists could be used for reference in designing novel derivatives of naftopidil with optimal pharmacological properties.
Adrenergic alpha-1 Receptor Antagonists ; Animals ; Antihypertensive Agents ; chemical synthesis ; chemistry ; pharmacology ; In Vitro Techniques ; Molecular Structure ; Piperazines ; chemical synthesis ; chemistry ; pharmacology ; Rabbits ; Structure-Activity Relationship ; Vasoconstriction ; drug effects

OBJECTIVETo investigate the effects of 17-β estradiol (E(2)) and Porphyromonas gingivalis (Pg) W83 on the expression of interleukin (IL)-6 and IL-8 in human periodontal ligament cells (hPDLC).

METHODSPrimary cultures of hPDLC were established and the cells of passage four were treated with 10(-10) mol/L E(2), 10(-7) mol/L E(2) or PgW83 individually or E(2) combined with PgW83. The expression levels of IL-6 and IL-8 protein at 12 h and 24 h were measured with enzyme-linked immunosorbent assay and the levels of mRNA at 24 h were detected with real-time reverse transcriptase polymerase chain reaction.

RESULTSThe expression level of IL-6 reached (2482.88 ± 26.53) ng/L in hPDLC treated with Pg at multiplicity of infection (MOI) of 100 for 24 h, which was significantly higher than that in hPDLC treated with Pg at MOI of 10:1 [(734.09 ± 87.90) ng/L, P = 0.000], the controls [(425.8 ± 77.25) ng/L, P = 0.000] and that in hPDLC treated with Pg at MOI of 100 for 12 h [(1157.50 ± 234.65) ng/L, P = 0.000]. The expression level of IL-8 reached (4965.81 ± 1072.55) ng/L in hPDLC treated with Pg at MOI of 100 for 24 h, which was significantly higher than that in hPDLC treated with Pg at MOI of 10 [(803.51 ± 162.08) ng/L, P = 0.007], the controls [(400.75 ± 2.27) ng/L, P = 0.005] and that in hPDLC treated with Pg at MOI of 100 for 12 h [(1431.12 ± 82.78) ng/L, P = 0.001]. E(2) did not show remarkable effect on the expressions of IL-6 and IL-8. E(2) combined with Pg (MOI = 100:1) significantly promoted the expression levels of IL-6 at 24 h while did not influence those of IL-8. The relative mRNA level of IL-6 in hPDLC treated with 10(-10) mol/L E(2) or 10(-7) mol/L E(2) combined with Pg were 0.49 ± 0.15 (P = 0.021)and 0.53 ± 0.16 (P = 0.036) individually, which were significantly higher than that treated with Pg alone, 0.19 ± 0.06. The protein level of IL-6 in hPDLC treated with 10(-10) mol/L E(2) or 10(-7) mol/L E(2) combined with Pg were (5512.66 ± 1022.07) ng/L (P = 0.012) and (6988.78 ± 2279.13) ng/L (P = 0.000) individually, which were significantly higher than that treated with Pg alone, (3138.46 ± 183.72) ng/L.

CONCLUSIONSPgW83 significantly increased the expression levels of IL-6 and IL-8 in hPDLC in a dose-and time-dependent manner. Without the infection of periodontal pathogens, estrogen may exert no effect on the expression of IL-6 and IL-8 while it may promote the expression of IL-6 in hPDLC when combined with Pg, which may in turn promote the process of periodontal inflammation.

Adolescent ; Adult ; Cells, Cultured ; Estradiol ; pharmacology ; Female ; Humans ; Interleukin-6 ; genetics ; metabolism ; Interleukin-8 ; genetics ; metabolism ; Male ; Periodontal Ligament ; cytology ; metabolism ; microbiology ; Porphyromonas gingivalis ; RNA, Messenger ; metabolism ; Young Adult

OBJECTIVETo investigate the clinical efficacy and safety of preferred use of high-frequency oscillatory ventilation (HFOV) in the treatment of neonatal pulmonary hemorrhage.

METHODSThe clinical efficacy of preferred use of HFOV (preferred use group) and rescue use of HFOV after conventional mechanical ventilation proved ineffective (rescue use group) in the treatment of 26 cases of neonatal pulmonary hemorrhage was retrospectively analyzed. The oxygenation index (OI), pulmonary hemorrhage time, hospitalization time, ventilation time, oxygen therapy time, complications, and outcome of the two groups were compared.

RESULTSCompared with the rescue use group, the preferred use group had significantly lower IO values at 1, 6, 12, 24, 48, and 72 hours after treatment (P<0.05). Compared with the rescue use group, the preferred use group had a significantly lower incidence of ventilator associated pneumonia (VAP) (P<0.05) and a significantly higher cure rate (P<0.05). There were no statistically significant differences in the incidences of pneumothorax, intracranial hemorrhage, and digestive tract hemorrhage between the two groups (P>0.05). Compared with those in the rescue use group, children who survived in the preferred use group had significantly shorter pulmonary hemorrhage time, hospitalization time, ventilation time, and oxygen therapy time (P<0.05).

CONCLUSIONSCompared with the rescue use of HFOV, preferred use of HFOV can better improve oxygenation function, reduce the incidence of VAP, shorten the course of disease, and increase cure rate while not increasing the incidence of adverse effects.

Female ; Hemorrhage ; therapy ; High-Frequency Ventilation ; adverse effects ; Humans ; Infant, Newborn ; Lung Diseases ; therapy ; Male ; Pneumonia, Ventilator-Associated ; prevention & control ; Retrospective Studies

Papillary adenoma (PA) of kidney is defined as a lesion measuring less than 15 mm and featuring papillary or tubular architecture along with nuclei of low grade.Clear cell renal cell carcinoma (CCRCC) is the most common seen group of malignant neoplasms consists of cells with clear or eosinophilic cytoplasm.The coexistence of these two kinds of tumor is rare and was only reported in one piece of literature to date.We report a thought-provoking case in which CCRCC is coexisting with multiple PAs.The CCRCC shows no difference with other common cases while the PAs share the same clinical and pathological features with other ones and demonstrates no amplifying of 3,7 or 17 chromosome.However,the multiple PAs were neglected by imaging doctors and surgeons,and some tiny lesions were not found until the observation under microscope.This case reminds that patients accepting partial nephrectomy for CCRCC may have PAs,so attention should be paid to the image studies along with routine pathological examination of kidney for that there may exists two or more kinds of lesions.

OBJECTIVETo study the ultrastructural changes of the rat convoluted seminiferous tubule after alcohol consumption.

METHODSForty-eight Wistar mature male rats were divided into two groups randomly: control group (A) and experimental one (B). 6 ml/(kg x d) of 50 degrees alcohol was perfused through the gastric tube for 39 days in Group B; and 6 ml/(kg x d) of normal saline was supplemented in Group A. The ultrastructure of the rat convoluted seminiferous tubule was observed by transmission electron microscope at day 14, 27 and 40.

RESULTSIn Group A, the pykno-basement membrane was unstriated and uniform, Sertoli cells showed cytoplasmic profusion, with big nucleus, well-distributed nucleoplasm, distinct nucleolus, more mitochondria and plain hierarchical tight-junction. And the ultrastructure of the rat convoluted seminiferous tubule in Group B began to change at the end of the first spermatogenic cycle (D 14) and changed more and more evidently with the ethanol administration, mainly as follows: (1) more lysosomes and vacuolisation found in Sertoli cells, and organelles decreased and blurry; (2) more and bigger vacuoles among the spermatogonia, Sertoli cells and basement membrane; (3) obvious apoptosis of spermatogonia and apoptotic bodies aggregated near the membrane; (4) more cytoplasm and vacuolisation in the sperm of the convoluted seminiferous tubule, and disarranged, deleted or clustered mitochondria in the sperm tail; (5) blurry and rigid tight-junction; (6) thickened, wrinkled or broken basement membrane and under-basement

CONCLUSIONAlcohol can cause ultrastructural changes of the basement membrane, tight-junction and Sertoli cells of the membrane. rat convoluted seminiferous tubule and apoptosis of spermatogonia.

Animals ; Apoptosis ; drug effects ; Basement Membrane ; drug effects ; pathology ; Ethanol ; toxicity ; Male ; Microscopy, Electron, Transmission ; Random Allocation ; Rats ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; ultrastructure ; Sertoli Cells ; drug effects ; pathology

Objective:To investigate the preliminary effects of sub-pectoral fascial breast augmentation and reconstruction.Methods:Six patients (10 breasts) of mammary dysplasia, mastatrophy, prophylactic mastectomy, unilateral breast defect with contralateral mastatrophy were included in the study from Oct. 2019 to July 2021. The mean patient age was 29 years (range, 20 to 35 years). All the textured and smooth cohesive gel implants were inserted under pectoralis major fascia by endoscopic-assisted, incisions were including axillary, around areola and inferior mammary fold approaches. The prophylactic mastectomy cases were performed nipple sparing mastectomy and sub-pectoral fascial breast restoration with implants. The fat and fascia tissue were well reserved to give a satisfying coverage of the appropriate implant. Negative pressure drainage and moulding dressing were used after the surgery.Results:Ten breast augmentation and restoration with a mean implant size of 200 cc (range, 180-300 cc). Less immediate postoperative pain and bleeding were reported. Patients were followed up for an average of 10 months (range, 6 to 21 months). There were no cases of major malpositions, double-bubble and bottom out symptoms. The overall outcome was with better symmetry and satisfaction with time passed by, and no secondary surgical procedures needed.Conclusions:Primary and satisfactory results have been obtained in subfascial breast augmentation and restoration for indications. With the endoscopic-assisted accurate pectoral fascial dissection, and well reserved soft tissue coverage, this technique could avoid the pectoralis major muscle ablation and keep the advantages of sub-glandular plane.

Objective To evaluate the influence of Circle of Willis on intravascular hypothermia. Methods A patient-specific model of the Circle of Willis was constructed based on the CT images and the in vitro perfusion experiment with cold water for 20 ℃ was performed. The water was injected from right intracarotid artery (ICA) to the area of middle cerebral artery (MCA) at the flow rate of 30 mL/min and made the cooling period last 15 min. The cooling and rewarming characteristics in the phantom and fluid around MCA were investigated using thermocouples arranged at 27 and 1 spatial locations. The areas distributed with cold water were further visualized using the dyed solution. Results The cold water from right ICA was mainly distributed to right anterior cerebral artery (ACA), MCA, and posterior communicating artery (PCoA), while only a little part of the water could possibly pass through anterior communicating artery (ACoA) to the left ACA. The nearer the locations to the area with cold water, the faster cooling down and also faster temperature recovery rate would be obtained. Moreover, the phantom temperature distributions were asymmetric around MCA due to the complicated bifurcation structures in this area. Conclusions This physical model is useful for investigating the influence of vasculature on endovascular hypothermia and applicable in designing patient-specific hypothermia therapy.

BACKGROUNDType 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.

METHODSThis cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level.

RESULTSIn patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37-4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47-38.03), dyslipidemia (OR 2.65, CI 1.54-4.56), diastolic blood pressure (OR 1.02, CI 1.00-1.04), and body mass index (OR 0.95, CI 0.92-0.99) are independent factors for early-onset T2DM.

CONCLUSIONSWe observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.

Adult ; Blood Glucose ; analysis ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; blood ; etiology ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Male ; Risk Factors ; Waist-Hip Ratio

Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P ＜0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P ＜0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P ＜ 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P ＜0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR＝ 2 .012 ,1 .637 , 1 .325 ,respectively ;all P ＜0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR ＝ 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P ＜0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .

PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers ; Cohort Studies* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Lymph Nodes ; Nasopharynx ; Plasma ; Prognosis ; Radiotherapy* ; Tumor Burden*