OBJECTIVETo investigate the neointima formation and the expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in cuff-induced vascular injury in mouse model, and to examine the effect of angiotensin II type 1 receptor (AT1) blocker, olmesartan, on MCP-1 and TNF-alpha expression and consequently vascular remodeling.

METHODSVascular injury was induced by polyethylene cuff-placement around the mouse femoral artery. Some mice were treated with AT1 receptor blocker, olmesartan, at the dose of 3 mg.kg(-1).day(-1) with an osmotic minipump. Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) were measured by morphometric analysis and bromodeoxyuridine (BrdU) incorporation. MCP-1 and TNF-alpha expression was detected by Western blot and immunohistochemical staining.

RESULTSWe observed neointima formation 14 days after cuff placement as well as VSMCs proliferation in the media and neointima. Cuff placement also induced MCP-1 and TNF-alpha expression in the media and neointima that the VSMCs specifically existed. Treatment of mice with olmesartan at a dose of 3 mg.kg(-1).day(-1), which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs. Olmesartan also inhibited MCP-1 and TNF-alpha expression in the injured arteries.

CONCLUSIONSOur results demonstrate that blockade of AT1 receptor inhibits MCP-1 and TNF-alpha expression and thereby improves vascular remodeling.

Analysis of Variance ; Animals ; Blotting, Western ; Cell Division ; drug effects ; physiology ; Cells, Cultured ; Chemokine CCL2 ; analysis ; Disease Models, Animal ; Imidazoles ; pharmacology ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes ; cytology ; drug effects ; Muscle, Smooth, Vascular ; cytology ; drug effects ; Neovascularization, Physiologic ; drug effects ; physiology ; Olmesartan Medoxomil ; Probability ; Sensitivity and Specificity ; Tetrazoles ; pharmacology ; Tumor Necrosis Factor-alpha ; analysis ; drug effects ; Tunica Intima ; drug effects ; pathology ; Vascular Diseases ; physiopathology

Objective To detect the serum levels of calpainin (S100A11) using nanomagicbeabs sorting-time resolved fluoroimmuno assay (NMBS-TRFIA) and evaluate its diagnostic value in pancreatic carcinoma.Methods 88 patients with pancreatic carcinoma,50 patients with acute pancreatitis,10 patients with pancreatic cyst and 20 healthy controls were selected as the study subjects.The human peripheral serum blood was sorted with S100A11 antibody coupled nanomagicbeabs,and the concentration of S100A11 was detected by TRFIA method.The area under the receiver operating characteristic (ROC) curve (AUC) was used to determine the cut-off level for diagnosis of pancreatic carcinoma,in order to evaluate the sensitivity and specificity for diagnosis of pancreatic carcinoma.Results S100A11 showed a linear relationship within the range of 6.08～ 500 ng/ml using NMBS-TRFIA method,intraassay CV≤6.35％,inter-assay CV≤7.12％,and the average recovery rate was 104.7％.The serum levels of S100A11 in patients with pancreatic carcinoma,patients with acute pancreatitis and patients with pancreatic cyst were 185.53 ± 161.19,106.06±113.83 and 68.99± 47.83 ng/ml respectively.Compared with the normal control group (37.98±25.14 ng/ml),the differences were statistically significant (t=-8.065,-3.375,-2.266,all P ＜0.01).The serum levels of S100A11 in patients with pancreatic carcinoma was significantly higher than those in patients with acute pancreatitis and patients with pancreatic cyst (all P＜0.05).According to the ROC curve,ROCAUC=0.985 (95％ CI:0.972 ～ 0.997),the best cut-off level for the diagnosis of pancreatic carcinoma was 89.5 ng/ml (sensitivity 81.8 ％,specificity 67.5 ％).Conclusion NMBS-TRFIA can enrich S100A11 in serum and improve the detection sensitivity of serum S100A11,and the method is simple and easy to be popularized.Serum S100A11 has a high sensitivity and specificity in the diagnosis of pancreatic carcinoma,and is a new serum marker for the diagnosis of early pancreatic carcinoma.

OBJECTIVE: To describe characteristic of hand-wrist bone development in adolescents of 14 years old in China, and to estimate trend of bone development of them. METHODS: A total of 109 adolescents of 14 years was selected as subjects (males: 53, females: 56). X-rays examination of their left hand-wrist bone were performed and analyzed. The development characteristics of each position in accordance with Gu's mapping of skeletal age were compared with Gu's results and ours. RESULTS: Compared with Gu's, osteoepiphysis of distal radius, the first metacarpal bone, the fourth proximal phalanx were more advanced in boys, osteoepiphysis of distal radius, the second-fifth metacarpal bones, the first-fifth proximal phalanxs, and the second-fifth middle phalanxs were more advanced in girls. CONCLUSION The results suggested that a forward trend of 14 years old adolescents bone development currently exists in our country, especially in girls. As an important age of criminal responsibility, this forward trend of development of bones among adolescents currently should be kept in mind when estimating bone age of criminals.
Adolescent ; Age Determination by Skeleton/methods* ; Bone Development/physiology* ; Female ; Forensic Anthropology ; Humans ; Male ; Metacarpal Bones/diagnostic imaging* ; Radius/diagnostic imaging* ; Wrist Joint/diagnostic imaging*

The critically ill coronavirus disease 2019 (Covid-19) patients usually present acute respiratory distress syndrome (ARDS), or even acute respiratory failure, and require mechanical ventilation (MV) to provide support for breathing. However, clinical studies have found an extraordinarily high mortality rate (>50%) for those Covid-19 patients who underwent MV. Considering the mechanical nature of MV, the high mortality rate is highly possible to be associated with mechanical stretch-induced lung injury during MV. Thus, it is imperative to understand the MV-induced pathological alterations in the respiratory system and corresponding mitigation measures in order to improve the therapy of critically ill Covid-19 patients. Ventilator-induced lung injury in therapy of critically ill Covid-19 patients involves several biomechanical factors and mechanisms, including changes in respiratory parameters, inflammatory cytokines storm, ciliary-mucus system, airway smooth muscle cells, lung fibrosis, and stretch-activated cell signaling. It is hoped that these biomechanical issues can be diligently investigated, so as to provide insights for optimizing the therapy for Covid-19 as well as other respiratory diseases.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

To evaluate the economics of Suhuang Zhike Capsules in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) for inpatients. Based on the published clinical research data, cost-utility analysis was used in this study to evaluate the pharmacoeconomics of Suhuang Zhike Capsules in treatment of AECOPD inpatients from the perspective of medical insu-rance. The test group was treated with Suhuang Zhike Capsules combined with conventional Western medicine, and the control group was treated with conventional Western medicine alone. Treeage software was used to construct a pharmacoeconomic model and perform simulation analysis. The results showed that the cost and output of Suhuang Zhike Capsules combined with the conventional Western medicine were 60 010.18 yuan and 1.92 quality adjusted life year(QALYs), respectively in the simulated 3 years of disease treatment. The cost and output of the conventional Western medicine were 96 730.60 yuan and 1.90 QALYs respectively. Suhuang Zhike Capsules combined with conventional Western medicine required lower cost but achieved higher output, showing cost-utility advantages, so this drug combination was a plan with pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is believed that as compared with the conventional Western medicine, Suhuang Zhike Capsules combined with conventional Western medicine have lower cost and higher output for the treatment of AECOPD inpatients, and it is a treatment plan with pharmacoeconomic advantages.
Capsules ; Drugs, Chinese Herbal/therapeutic use* ; Economics, Pharmaceutical ; Humans ; Inpatients ; Pulmonary Disease, Chronic Obstructive/drug therapy*

Borneol (Bo) and Arg-Gly-Asp (RGD) co-modified docetaxel (DTX) loaded MPEG-PLGA nanoparticles (DTX-Bo-RGD-NPs) were prepared to improve the therapeutic effect of DTX against glioma after intranasal administration. DTX-Bo-RGD-NPs were prepared by emulsification-solvent evaporation method, and their morphology, particle size, zeta potential, drug loading capacity (DLC), stability, and in vitro release properties were investigated. The fluorescence probe coumarin-6 loaded NPs were prepared for investigating the NPs' uptake property on C6 and 16HBE cell models to evaluate in vitro targeting ability. The DiR loaded NPs were prepared for observing the fluorescence intensity at the brain tumor site after intranasal administration through in vivo imaging system in a C6 rat orthotropic model, evaluating the targeting ability in vivo. The anti-tumor effects of DTX-Bo-RGD-NPs were also investigated in such C6 rat orthotropic model in vivo. Animal welfare and experimental procedures are in compliance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The results showed that DTX-Bo-RGD-NPs were spherical and uniformly distributed, with a particle size of about 140 nm and a zeta potential of -20 to -30 mV. The drug delivery system showed good stability and sustained release property in vitro, and favorable brain tumor targeting effect in vitro and in vivo. Such novel drug delivery system significantly improved the accumulation of DTX-Bo-RGD-NPs in tumor sites and displayed a higher brain tumor targeting efficiency, providing promising therapeutics of DTX for the treatment of glioma after intranasal administration.

This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.
Coronary Disease/drug therapy* ; Drugs, Chinese Herbal ; Economics, Pharmaceutical ; Female ; Humans

The aim of the research was to evaluate the efficacy and safety associated with Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD). We searched 8 electronic databases up to November 2020, including PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP and SinoMed. Eligible studies were clinical trials of Shexiang Tongxin Dropping Pills combined with conventional therapy used in the treatment of coronary heart disease(CHD). The Meta-analysis was performed using STATA 15 software. A total of 21 RCTs(n=2 186) were shortlisted for the Meta-analysis. The results of efficacy evaluation showed that the total effective rate of Shexiang Tongxin Dropping Pills combined with conventional therapy was higher than that of conventional therapy of coronary heart disease(RR=1.20, 95%CI[1.15, 1.26], Z=8.63, P<0.001). Furthermore, Shexiang Tongxin Dripping Pills combined with conventional therapy had better effect on electrocardiogram efficacy(RR=1.24, 95%CI[1.16, 1.34], Z=5.98, P<0.001) and the number of angina attacks(SMD=-2.30, 95%CI[-3.47,-1.14], Z=3.88, P<0.001), the duration of angina attack(SMD=-2.31, 95%CI[-3.07,-1.55], Z=5.97, P<0.001), with lower levels of LDL-C(SMD=-0.73, 95%CI[-1.32,-0.14], Z=2.42, P=0.016), TC(SMD=-1.16, 95%CI[-1.35,-0.96], Z=11.56, P<0.001) and TG(SMD=-0.87, 95%CI[-1.06,-0.68], Z=8.97, P<0.001), and higher levels of HDL-C(SMD=0.87, 95%CI[0.02, 1.71], Z=2.00, P=0.045). The results of safety evaluation showed that the incidence of adverse reactions of Shexiang Tongxin Dropping Pills combined with conventional therapy was lower than that of conventional therapy of coronary heart disease(RR=0.45, 95%CI[0.22, 0.91], Z=2.23, P=0.026). There were significant differences in the above outcome indexes between the two groups. After the Harbord method test, the total effective rate outcome index has publication bias, but the sensitivity analysis of the cut-and-fill method suggested that the result was stable. In general, limited by the quantity and quality of included literature, more high-quality studies are needed to further verify the conclusions of this study.
Angina Pectoris ; Coronary Disease/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Electrocardiography ; Humans