Synthesis and anti-HCC activity of full 2ʹ-F/OMe-siRNA encapsulated with neutral cytidinyl/cationic lipid / 药学学报

A variety of full 2ʹ-F/OMe-modified siRNAs were designed and synthesized, and the activity against hepatocellular carcinoma Huh-7 and HepG2 cells was evaluated. K&A DNA/RNA H-8 synthesizer was used to synthesize siRNAs, and neutral cytidinyl lipid DNCA mixed with cationic lipid CLD were used to transfect siRNA. By RT-qPCR and CCK-8 assay, the target gene silence and the proliferation of Huh-7 and HepG2 cells were detected. The siRNAs loading into Ago2 protein was detected by RNA-binding protein immunoprecipitation. Drug uptake and cell apoptosis were detected by flow cytometry, and the expression of PLK1 protein was detected by Western blot. Partial full 2ʹ-F/OMe modified siRNAs, especial siPLK1A3, increased the uptake of Huh-7 cells, enhanced their binding to Ago2 and gene silencing activity, down-regulated PLK1 protein, as well as induced more Huh-7 cell apoptosis and proliferation inhibition activity. It provides important data for the development of novel siRNA modification patterns and anti-HCC formulations.

Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice / 中华内科杂志

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) μg/mg vs. (0.974±0.060) μg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) μg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.

Efficacy of transcatheter pulmonary valve perforation in neonates with pulmonary atresia with intact ventricular septum / 中华儿科杂志

Objective: To explore the efficacy and safety of transcatheter pulmonary valve perforation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The clinical data on surgical treatment and follow-up in 16 patients with PA-IVS who underwent transcatheter pulmonary valve perforation in Women and Children's Hospital, Qingdao University from October 2018 to October 2021 were analyzed retrospectively. The right ventricular systolic pressure and percutaneous oxygen saturation (SpO2) were compared before and after operation. In addition, the SpO2 and echocardiographic data at preoperative and the last follow-up were compared. Comparisons between groups were performed using paired-samples t test. Results: Among the 16 patients (10 males and 6 females) with the age at operation of 19 (14, 26) days, 12 cases underwent transcatheter pulmonary valve perforation successfully, 2 cases were transferred to surgery department for open-heart pulmonary valvulotomy, and the remaining 2 cases were transmitted to surgery department for transthoracic pulmonary valve perforation. The age at operation of the 12 patients who underwent transcatheter pulmonary valve perforation was 18 (14, 27) days, and the weight was (3.6±0.4) kg. The immediate postoperative right ventricular systolic pressure decreased significantly ((57±16) vs. (95±19) mmHg (1 mmHg=0.133 kPa), t=7.49, P<0.001), and the postoperative SpO2 was improved effectively (0.90±0.48 vs.0.75±0.09, t=-5.61, P<0.001). The follow-up time was 22 (7, 33) months for 12 patients who underwent transcatheter pulmonary valve perforation successfully. At the last follow-up, the ratio of right to left ventricular transverse diameter was significantly higher than that before operative (0.55±0.05 vs. 0.45±0.05, t=-3.27,P=0.007). Furthermore, the Z-scores of pulmonary valvular diameter (-0.78±0.23 vs. -1.73±0.56, t=-8.52, P<0.001) and the tricuspid valvular diameter (-0.52±0.12 vs. -1.46±0.38, t=-10.40, P<0.001) were all significantly higher than preoperative data. At last, all the patients achieved biventricular circulation without death or major complications. Conclusion: Transcatheter pulmonary valve perforation is a safe and effective therapy for neonatal PA-IVS, and its curative effect has been confirmed by the medium follow-up data.

Integrated management during the perinatal period for total anomalous pulmonary venous connection / 中国当代儿科杂志

OBJECTIVES@#To evaluate the clinical effectiveness of integrated management during the perinatal period for fetuses diagnosed with total anomalous pulmonary venous connection (TAPVC) by prenatal echocardiography.@*METHODS@#Clinical data of 64 cases of TAPVC fetuses diagnosed by prenatal echocardiography and managed with integrated perinatal care in Qingdao Women and Children's Hospital from January 2017 to December 2021 were retrospectively analyzed. Integrated perinatal care included multidisciplinary collaboration among obstetrics, fetal medicine, ultrasound, pediatric cardiology, pediatric anesthesia, and neonatology.@*RESULTS@#Among the 64 TAPVC fetuses, there were 29 cases of supracardiac type, 27 cases of intracardiac type, 2 cases of infracardiac type, and 6 cases of mixed type. Chromosomal analysis was performed in 42 cases, and no obvious abnormalities were found. Among the 64 TAPVC fetuses, 37 were induced labor, and 27 were followed up until term birth. Among the 27 TAPVC cases, 2 cases accepted palliative care, 2 cases were referred to another hospital for treatment and lost to follow-up, while the remaining 23 cases underwent primary repair surgery. One case died within 6 months after the operation due to low cardiac output syndrome, while the other 22 cases were followed up for (2.1±0.3) years with good outcomes (2 cases underwent a second surgery within 1 year after the first operation due to anastomotic stenosis or pulmonary vein stenosis).@*CONCLUSIONS@#TAPVC fetuses can achieve good outcomes with integrated management during the perinatal period.

Interleukin 6 induces osteogenic differentiation and calcification of human umbilical artery smooth muscle cells via trans-signaling pathway / 中华风湿病学杂志

Objective:To explore the trans-membrane signaling mechanism of interleukin-6 (IL-6)-induced osteogenic differentiation and calcification of human umbilical artery smooth muscle cells (HUASMCs).Methods:HUASMCs were primarily cultured in vitro and were stimulated with IL-6, IL-6+solutable IL-6 receptor (sIL-6R), IL-6+sIL-6R+solutable gp130 (sgp130), or vehicle (blank control). Alizarin red and Von Kossa staining were used for detecting cell calcification, Western blot was used to test the protein expression of tissue-nonspecific alkaline phosphatase (TNAP), osteopontin (OPN), bone morphogenetic protein-2 (BMP-2) and Runt related transcription factor 2 (Runx2), and immunofluorescence was used to examine the mIL-6R expression of HUASMCs. The comparison of measurement date between the two groups was conducted by t-test. The comparison of measurement date between multiple groups was conducted by one-way analysis of variance (ANOVA). Results:The intensity severity of calcification stain was IL-6+sIL-6R group >IL-6+sIL-6R+sgp130 group>IL-6 group=blank control. After stimulated for 12 hours, the TNAP expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.44±0.08), (0.52±0.14), (0.84±0.16) and (0.55±0.10) respectively ( F=290.96, P<0.001). After stimulated for 3 days, the OPN expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.61±0.84), (0.95±0.16), (1.65±0.24) and (0.99±0.10) respectively ( F=507.72, P<0.001). After stimulated for 12 hours, the BMP-2 expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.77±0.05), (1.69±0.16), (2.81±0.26) and (0.57±0.12) respectively ( F=959.09, P<0.001). After stimulated for 3 days, the Runx2 expression in blank control, IL-6 group, IL-6+sIL-6R group,IL-6+sIL-6R+sgp130 group were (0.57±0.03) , (0.92±0.10), (1.31±0.13) and (0.66±0.06) respectively ( F=1141.27, P<0.001). Comparing with Jurkat cells (positive control) and CEM cells (negative control), HUASMCs limited expressed mIL-6R. Conclusion:IL-6 may induce HUASMCs osteogenic differentiation and calcification mainly via the sIL-6R-mediated trans-signaling pathway.

Association between duration of fever before treatment and intravenous immunoglobulin resistance in Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#To examine the association between duration of fever before intravenous immunoglobulin (IVIG) treatment and IVIG resistance in children with Kawasaki disease (KD).@*METHODS@#A retrospective analysis was performed on the medical data of 317 children with KD who were admitted from January 2018 to December 2020. According to the duration of fever before IVIG treatment, they were divided into two groups: short fever duration group (≤4 days) with 92 children and long fever duration group (>4 days) with 225 children. According to the presence or absence of IVIG resistance, each group was further divided into a drug-resistance group and a non-drug-resistance group. Baseline data and laboratory results were compared between groups. A multivariate logistic regression analysis was used to identify the influencing factors for IVIG resistance.@*RESULTS@#In the short fever duration group, 19 children (20.7%) had IVIG resistance and 5 children (5.4%) had coronary artery aneurysm, and in the long fever duration group, 22 children (9.8%) had IVIG resistance and 19 children (8.4%) had coronary artery aneurysm, suggesting that the short fever duration group had a significantly higher rate of IVIG resistance than the long fever duration group (P<0.05), while there was no significant difference in the incidence rate of coronary artery aneurysm between the two groups (P>0.05). In the short fever duration group, compared with the children without drug resistance, the children with drug resistance had a significantly lower level of blood sodium and significantly higher levels of procalcitonin, C-reactive protein, and N-terminal B-type natriuretic peptide before treatment (P<0.05). In the long fever duration group, the children with drug resistance had significantly lower levels of blood sodium and creatine kinase before treatment than those without drug resistance (P<0.05). The multivariate logistic regression analysis showed that a reduction in blood sodium level was associated with IVIG resistance in the long fever duration group (P<0.05).@*CONCLUSIONS@#IVIG resistance in children with KD varies with the duration of fever before treatment. A reduction in blood sodium is associated with IVIG resistance in KD children with a duration of fever of >4 days before treatment.

Natural compounds modulate the autophagy with potential implication of stroke

Stroke is considered a leading cause of mortality and neurological disability, which puts a huge burden on individuals and the community. To date, effective therapy for stroke has been limited by its complex pathological mechanisms. Autophagy refers to an intracellular degrading process with the involvement of lysosomes. Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents. Increasing evidence support that autophagy protects neuronal cells from ischemic injury. However, under certain circumstances, autophagy activation induces cell death and aggravates ischemic brain injury. Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke. In the present work, we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

Clinical study of age-related sensory innervation of the anterior hard palate / 华西口腔医学杂志

OBJECTIVES@#The present study aimed to explore the innervation of the anterior hard palatine and its relationship with individual development stage. Specifically, the effects of anesthesia on patients of different ages were observed, and neurodevelopment in the maxillofacial region was invesitgated. References that are helpful in selecting local anesthesia were provided.@*METHODS@#A total of 182 patients with mixed dentition were randomly divided into the nasopalatine nerve block and greater palatine nerve block groups. Then, 219 patients with permanent dentition were divided into an adolescent group (13-18 years old) and adult group (over 19 years old), all of whom underwent bilateral greater palatine nerve block. Palatal mucosal pain sensation was tested pre- and post-anesthesia with Von Frey hairs.@*RESULTS@#Among the children with mixed dentition, bilateral greater palatine nerve block tended to result in better anesthetic effects than nasopalatine nerve block (@*CONCLUSIONS@#The sensation of the anterior hard palatine seems mainly dominated by the greater palatine nerve until mixed dentition and gradually shifted to the nasopalatine nerve in conjunction with maxillary development and tooth replacement. Hence, the innervation of the anterior hard palatine induce a secondary development during the development of the maxilla.

Protective effect of astaxanthin on the retinopathy of type 1 diabetic rats / 中华实验眼科杂志

Objective:To investigate the protective effect of astaxanthin on the retinopathy in rats with type 1 diabetes and related mechanism.Methods:Thirty-six male SPF rats received intraperitoneal injection of 1% streptozotocin (STZ) to prepare type 1 diabetes model.The rats were randomly assigned to the diabetes group, low dose astaxanthin group and high dose astaxanthin group by a random number table.The rats in the low dose astaxanthin group and high dose astaxanthin group received respectively astaxanthin 20 mg/kg and 100 mg/kg by gavage everyday.The rats in the diabetes group received an equal volume of olive oil.Twelve rats received an equal volume of sodium citrate as the control group.Blood glucose and body mass were measured every 2 weeks.After 24 weeks, the retina was digested to make retinal capillary network preparation.The number of pericytes and acelluar strands was compared among the different experimental groups.The relative expressions of anti-inflammatory cytokines in retinal tissue were detected by immunohistochemistry, real-time PCR and Western blot.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results:Body mass of the rats in the low dose astaxanthin group and high dose astaxanthin group was significantly higher than that in the diabetes group (both at P<0.05). Blood glucose levels in the low dose astaxanthin group and high dose astaxanthin group were significantly lower than that in the diabetes group (both at P<0.05). In the control group, main artery was round, uniform, and strongly stained.The vein was lightly stained and had a large diameter.In the diabetes group, retinal arteriovenous trunk and branches appeared tortuous at a low magnification, with capillary network disorder.The morphology of the capillaries showed pathology in the low dose astaxanthin group and high dose astaxanthin group, but the vascular tortuosity, dilatation and stenosis were reduced in comparison with the diabetes group.The number of pericytes was 466.4±23.2, 207.3±31.7, 298.1±27.1 and 312.2±19.5 among different groups, with a significant difference among them ( F=34.420, P=0.047). The number of acelluar strands were 5.2±2.3, 32.9±12.7, 14.5±9.1 and 16.5±3.5 among different groups, with a significant difference among them ( F=47.340, P=0.021). The relative expression of IL-6, TNF-α and caspase-3 mRNA in the low dose astaxanthin group was 0.87±0.23, 0.91±0.34 and 1.07±0.15, the relative expression in the high dose astaxanthin group was 0.81±0.31, 0.85±0.39 and 0.95±0.11, which was significantly decreased in comparison with the diabetes group (1.63±0.47, 1.57±0.53 and 1.51±0.32) (all at P<0.05). The relative expression of IL-6, TNF-α and caspase-3 protein in the low dose astaxanthin group was 0.63±0.33, 0.51±0.14 and 0.60±0.13, the relative expression in the high dose astaxanthin group was 0.69±0.22, 0.49±0.15 and 0.57±0.22, which was significantly decreased in comparison with the diabetes group (all at P<0.05). Conclusions:Astaxanthin may play an important role in protecting pericytes from apoptosis and delaying development and progression of diabetic retinopathy in rats.Additionally, astaxanthin can inhibit release of anti-apoptosis and anti-inflammatory cytokines.

Clinical features of children with recurrent Kawasaki disease: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with recurrent Kawasaki disease (KD).@*METHODS@#PubMed, Web of Science, Embase, CNKI, Wanfang Med Online, and Weipu Data were searched for case-control studies on the clinical features of initial and recurrent KD. The articles were screened according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the Meta analysis. Effect models were selected based on the results of heterogeneity test, and then pooled @*RESULTS@#A total of 9 case-control studies were included, with 12 059 children with KD in total, among whom 206 children had recurrent KD (127 boys/61.7%; 79 girls/38.3%). The results of the Meta analysis showed that compared with the initial KD onset, the children with recurrent KD had a shorter duration of fever (@*CONCLUSIONS@#Current evidence shows that children with recurrent KD tend to have a shorter duration of fever and a lower incidence of swelling of the hands and feet. KD recurrence is more common in boys. Current evidence does not show an increased risk of developing coronary artery lesions in children with recurrent KD.

Content Determination of 10 Kinds of Active Componets in Tibetan Medicine Siwei Jianghuang Prescription and Its Decoction Technology Optim ization / 中国药房

OBJECTIVE：To e stablish the method for simultaneous determination of 10 kinds of active components in Tibetan medicine Siwei jianghuang prescription ，and to optimize its decoction technology. METHODS ：HPLC method was adopted. Using soaking time ，the amount of added water ，decoction time and decoction times as factors ，comprehensive score of the contents of 10 kinds of components and solid extracts rate as response values ，one the basis of single factor test ，Box-Behnken response surface method was used to optimize its decoction technology. RESULTS ：The linear range of gallic acid ，corilagin，magnoflorine， ellagic acid ， hydrochloric jatrorrhizine ， hydrochloride palmatine ， hydrochloride berberine ， bisdemethoxycurcumin， demethoxycurcumin and curcumin were 0.280 6-1.683 6，0.289 6-1.737 6，0.320 8-1.924 8，0.116 0-0.696 0，0.018 9-0.113 5， 0.013 3-0.079 9，0.092 3-0.553 8，0.025 5-0.153 0，0.036 1-0.216 3，0.041 0-0.245 7 µg（all r were 0.999 9），respectively. The limits of quantitation were 0.28，14.48，3.21，11.60，1.89，4.44，0.46，0.26，0.36，0.41 ng，respectively. The limits of detection were 0.11，4.14，1.24，3.32，0.58，1.33，0.13，0.09，0.14，0.12 ng，respectively. RSDs of precision ，stability and reproducibility tests were all lower than 3％. The recoveries were 92.56％-103.69％（RSDs were 0.90％-3.81％，n＝6）. The optimal decoction technology included soaking 60 min，adding 8-fold（mL/g）water，decoction for twice ，lasting for 65 min each time. In 6 validation tests ，comprehensive scores were 3.323 2-3.422 4，and the absolute value of the relative error with the predicted value （3.437 4）was less than 2％.CONCLUSIONS：Established method is simple and repeatable ，and can be used for simultaneous determination of 10 kinds of active components in Siwei jianghuang prescription. Optimized decoction technology is stable and feasible.

Prognosis of teeth with external root resorption caused by adjacent impacted teeth / 华西口腔医学杂志

OBJECTIVE@#This study aimed to investigate the prognosis of permanent teeth with external root resorption (ERR) caused by adjacent impacted teeth.@*METHODS@#A total of 75 ERR teeth (permanent teeth) caused by adjacent impacted teeth of 63 patients were included. The prognosis of ERR teeth was analyzed followed by minimally invasive extraction of the adjacent impacted teeth. The time of follow-up was six months. The relationship between prognosis of ERR teeth and patients' age, gender, root number, type of root resorption and degree of root resorption were analyzed.@*RESULTS@#In the 75 ERR teeth, 67 teeth (89.3%) did not show pulpitis symptoms. The clinical outcome was found to be related with age (r=0.330, P0.05). Pulpitis symptom was not found in ERR teeth of patients under 30 years old.@*CONCLUSIONS@#For ERR teeth caused by adjacent impacted teeth, keeping the pulp vital after surgical removal of impacted teeth is highly probable. Post-operative follow-up instead of preventive root canal therapy of ERR teeth is recommended.

Research progress on the modification of guided bone regeneration membranes / 华西口腔医学杂志

Guided bone regeneration (GBR) is an important technique to solve bone defect problems. In this technique, GBR barrier membranes play an irreplaceable role. GBR membranes can act as a barrier protecting fibroblasts from bone defects and promote osteoblast adhesion and proliferation, leading to bone regeneration. GBR barrier membranes should be enhanced because of the disadvantages of collagen membranes, which are extensively applied to the field of GBR. Therefore, various efforts have been devoted to modifying the antibacterial and osteogenic properties of GBR barrier membranes and developing novel materials. This article reviews the research advancements on the modification of GBR barrier membranes and discover future directions for the development of GBR barrier membranes to provide a reference for bone tissue engi-neering and repair.

Impaired Hypothalamic Regulation of Sympathetic Outflow in Primary Hypertension / 神经科学通报·英文版

The hypothalamic paraventricular nucleus (PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source of excitatory drive to the sympathetic outflow through innervation of the brainstem and spinal cord in hypertension. We discuss current findings on the role of the PVN in the regulation of sympathetic output in both normotensive and hypertensive conditions. The PVN seems to play a major role in generating the elevated sympathetic vasomotor activity that is characteristic of multiple forms of hypertension, including primary hypertension in humans. Recent studies in the spontaneously hypertensive rat model have revealed an imbalance of inhibitory and excitatory synaptic inputs to PVN pre-sympathetic neurons as indicated by impaired inhibitory and enhanced excitatory synaptic inputs in hypertension. This imbalance of inhibitory and excitatory synaptic inputs in the PVN forms the basis for elevated sympathetic outflow in hypertension. In this review, we discuss the disruption of balance between glutamatergic and GABAergic inputs and the associated cellular and molecular alterations as mechanisms underlying the hyperactivity of PVN pre-sympathetic neurons in hypertension.

TanshinoneⅡA attenuates carotid artery atherosclerosis by deactivating mast cells in adventitia / 中华心血管病杂志

Objective@#To investigate the effects of tanshinone ⅡA on atherosclerosis plaque formation and adventitial mast cells activation in high-fat-diet induced Apo E-/- mice model.@*Methods@#Sixteen 8-week-old Apo E-/-male mice and eight 8-week-old C57BL/6 male mice were randomly allocated into following group: the control group (C57BL/6 + carboxymethyl cellulose per gavage), the atherogenic group (Apo E-/-+carboxymethyl cellulose per gavage) and the tanshinoneⅡA intervention group (Apo E-/-+30 mg/kg tanshinone ⅡA per gavage). All three groups were fed with high-fat-diet for 26 weeks. Tanshinone ⅡA/carboxymethyl cellulose was applied by the method of gavage administration 6 weeks before execution. After 26 weeks, tumor necrosis factor-α (TNF-α) andinterleukin (IL)-6 levels in serum were assessed by ELISA. Carotid artery was removed, fixed with paraformaldehyde, embedded with paraffin and sectioned. Percentage of stenosis was evaluated on HE stained sections. Plaque progression was assessed by Movat staining. Toluidine blue staining was used to evaluate mast cells infiltration and activation. Immunochemistry staining was used to assess 5-HT, TNF-α and IL-6 expression. mRNA expression of mast cell marker Fcer1a in adventitial tissue was detected by real time-PCR.@*Results@#After high-fat-diet for 26 weeks, the mice in the atherogenic group showed advanced atherosclerosis, tanshinoneⅡA intervention reduced the percentage of carotid artery stenosis caused by atherosclerotic plaque formation ((58.48±8.07)% vs. (80.31±4.08)%, P<0.05). Compared with the atherogenic group, tanshinone ⅡA intervention group had lower level of TNF-α ((12.39±1.62)pg/ml vs. (17.44±1.42)pg/ml) and IL-6 ((116.24±12.16)pg/ml vs. (166.05±19.09)pg/ml) in serum, lower TNF-α ((20 145±1 556) vs. (25 288±1 671)) and IL-6 ((25 688±1 604) vs. (35 286±4 198)) expression in adventitia (all P<0.05). TanshinoneⅡA intervention also decreased the number of mast cells infiltration and activation, reduced 5-HT expression and mast cell marker Fcer1a mRNA relative expression in adventitia (all P<0.05).@*Conclusions@#Tanshinone ⅡA could attenuate induced by high-fat-diet carotid artery atherosclerosis in Apo E-/- mice. The protective effect of tanshinoneⅡA is probably mediated through reducing the number and activation percentage of mast cells, decreasing the release of inflammatory cytokines and inflammation of carotid artery in adventitia.

Pulmonary artery denervation to treat idiopathic pulmonary arterial hypertension in children:A case report and literature review / 中国实用儿科杂志

OBJECTIVE: To explore the safety and feasibility of pulmonary artery denervation(PADN)in children with idiopathic pulmonary hypertension(IPAH). METHODS: On July 11,2019,PADN was performed in Qingdao Women and Children's Hospital on the bifurcation of main pulmonary artery and the opening of left and right pulmonary artery in a child with IPAH. The pressure and resistance of pulmonary artery were monitored after operation. RESULTS: The pressure and resistance of pulmonary artery decreased significantly immediately after PADN. No serious complications occurred.CONCLUSION: PADN may be safe and feasible for children with IPAH. Further follow-up and multi-center registry study is necessary to confirm the efficacy and feasibility of PADN.

The effect of neovascularization in carotid plaque on clinical manifestations / 中华普通外科杂志

Objective To explore the effect of angiogenesis in carotid atherosclerotic plaque.Methods From Jan 2016 to Aug 2016,Carotid artery plaque was abtained in 52 cases after carotid endarterectomy at the Department of Cardiovascular Surgery of China-Japan Friendship Hospital.Patients were divided into symptomatic group and asymptomatic group.Specimens were stained with HE and Movat,and the density,size,distribution and morphology of neovascularization were counted.Results The density of neovascularization in the symptomatic group and the asymptomatic group were 5.27 ± 0.46 and 2.30 ±0.29,respectively (P ＜ 0.001),the average cross-sectional area of neovascularization in the symptomatic group was (2.26±0.21) mm2 and (1.00 ±0.48) mm2 in the asymptomatic group (P=0.02).In the distribution,the symptomatic group and the asymptomatic group were 3.37 ± 0.46/ mm2,1.32 ±0.16/mm2 in basal part,3.71 ±0.42/mm2,1.56 ±0.20/mm2 in the shoulder part,3.48 ±0.44/mm2,1.55 ± 0.21/ mm2 in the fibrous cap,respectively (P ＜ 0.001).Conclusion The density and cross-sectional area of neovascularization in the symptomatic group were larger than those in the asymptomatic group,irregular branching vessels were dominant.

Evaluation on safety of puerarin injection in clinical use / 中国中药杂志

Puerarin injection is commonly used in clinical treatment of coronary heart disease, angina pectoris, retinal artery, vein occlusion, sudden deafness and so on. This paper is aimed to evaluate the safety of puerarin injection in clinical use and explore the related factors that may cause its adverse reactions (ADRs), so as to find the warning signal of safety medication in time, put forward early warning, make early judgment and treatment, and ensure the safety of drug use. By strengthening surveillance, the best medication plan was established to prevent the occurrence of adverse reactions of puerarin injection and enhance people's awareness on the safety of puerarin injection. Database were searched to collect literature related to ADRs of puerarin injection. The data were extracted and analyzed by decision tree with treeage software and ² test was used to verify the data. A total of 62 papers involving 129 cases were included. The results showed that ADRs occurred mostly in patients aged 50-79 years, with the immune system and blood system accounting for the majority (88.3%), and ADRs occurred mostly 48 h after drug administration (61.1%). The severity of ADRs was not related to the dosage of puerarin, but it was related to the choice of the infusion solvent. In puerarin injection, most of the ADRs were moderate or severe (64.3%), 13 out of 129 cases were of death. Therefore, the indications and methods of use should be strictly controlled, and the allergic history of patients should be carefully questioned before medication to strengthen the monitoring of drug use.

Relationship between initial archwire materials and pain at the initial stage of orthodontic treatment: a systematic review and network Meta-analysis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This review aims to assess the relationship between initial archwire materials and pain at the initial stage of orthodontic treatment.</p><p><b>METHODS</b>On October 1, 2017, seven databases were searched electronically for studies oninitial archwire materials and pain at the initial stage of orthodontic treatment. Quality assessment was performed with bias risk assessment tools suggested by Cochrane's handbook. Data extraction of included studies was also carried out. Network Meta-
analysis was conducted using R 3.4.2 (with JAGS 4.3.0), GeMTC 0.14.3, and STATA 11.0.</p><p><b>RESULTS</b>Five studies with 330 participants were included, comparing four different materials: multi-stranded stainless steel, conventional nickel-titanium, super-elastic nickel-titanium, and thermal heat-activated nickel-titanium. Two studies were at low risk of bias, one was at high risk of bias, and the remaining two were at unclear risk of bias. Network Meta-analysis results showed no statistical differences of pain among the four initial archwire materials at day 1 and day 7. However, the most painless material was most likely to be thermal heat-activated nickel-titanium on rank probability.</p><p><b>CONCLUSIONS</b>On statistical probability, thermal heat-activated nickel-titanium initial arch wires is most likely to cause the least pain at the initial stage of orthodontic treatment, compared with other materials.</p>

Exploration of Service Objects Extension of Psychiatric Hospitals in Internet Era / 中国医院管理

The method of using internet to take advantages of tertiary psychiatric hospitals is explored.Tertiary psychiatric hospitals expand the service objects,improve the accessibility of mental health services,and realize the mental health care services extension and high-quality medical resources sinking by signing the technical guide agreement with primary health care institutions and internet plus,to explore a new type integrated management mode of mental diseases prevention,treatment and rehabilitation based on the psychiatric specialized hospitals.