Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

This study is to explore the mechanism of Xueshuantong improving cerebral microcirculation disorder through the combination of network pharmacology and experimental validation in vivo. Structural formulas of main Panax notoginseng saponins, including notoginsenoside R1, and ginsenoside Rg1, Re, Rb1 and Rd were obtained from Pubchem website and their potential targets were predicted by Swiss Target Prediction database. Potential molecular targets of brain microcirculation disorder were acquired from OMIM and GeneCards database. The overlapped molecular targets between the drug and disease were analyzed. Protein interaction analysis and topology maps were constructed through the STRING online analysis platform and Cytoscape software. Core action targets were selected. GO function and KEGG pathway were analyzed by DAVID database. Immunohistochemical method was used to examine the expression of platelet endothelial cell adhesion molecule-1 (CD31) in the ischemic cortex of middle cerebral artery occlusion and reperfusion (MCAO/R) rats. The levels of mRNA and protein expressions of core action targets in MCAO/R model rats′ brain microvessels were verified by RT-qPCR and Western blot. Based on network pharmacology, 242 targets of Xueshuantong, 425 targets of brain microcirculation disorder, and 35 overlapped targets were obtained. The potential key targets of Xueshuantong, protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), caspase 3 (CASP3), matrix metallopeptidase 9 (MMP-9), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), signal transducer and activator of transcription 3 (STAT3) involved in the alleviation of cerebral microcirculation disorder were obtained by setting degree and betweenness centrality as screening parameters. Xueshuantong at the dose of 48 mg·kg^-1 was shown to significantly improve the injury of neurological behaviors, as well as the density and morphology of microvessels of MCAO/R model rats. Xueshuantong could down-regulate the mRNA levels of AKT1, MMP-9, and STAT3, increase the protein expression levels of CD31, phosphorylated AKT and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and the ratio of B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/Bax), but decrease the protein expression levels of MMP-9, cleaved caspase-3 and phosphorylated STAT3. In summary, Xueshuantong could improve ischemic cerebral microcirculation disorder and thereby reduce nerve damage in ischemia-reperfusion rats by regulating signaling pathways related with PI3K, AKT, MMP-9, STAT3 and caspase-3 in microvessels. The study strictly adhered to all ethical protocols that experimental animals should follow in the course of medical research.

Objective:To establish ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） for simultaneous determination of six hepatotoxic pyrrolizidine alkaloids in Verbenae Herba， and to carry out preliminary risk assessment according to the research results. Method:An ACQUITY UPLC HSS T3 column （2.1 mm×100 mm， 1.8 μm） was used for analysis with 0.05% formic acid and 2.5 mmol·L^-1 ammonium formate in water （A）-0.05% formic acid and 2.5 mmol·L^-1 ammonium formate in acetonitrile （B） as mobile phase for gradient elution （0-12 min， 3%-8%B； 12-25 min， 8%-15%B； 25-26 min， 15%-3%B； 26-30 min， 3%B）， the flow rate was 0.3 mL·min^-1， the column temperature was 40 ℃， and the injection volume was 1 μL. MS system was operated by electrospray ionization （ESI） in the positive ion mode with multiple reaction monitoring mode. MS parameters of triple quadrupole and six analytes were optimized for qualitative and quantitative analysis. According to the determination results， the risk assessment was carried out by using margin of exposure （MOE） combined with transfer rate of hot water extraction. Result:Based on the instrument precision， linear range， repeatability， stability， recovery and other methodological validations， the results were in conformity with relevant standards of quantitative analysis. The linear ranges of intermedine， lycopsamine， intermedine N-oxide， lycopsamine N-oxide， echimidine N-oxide and echimidine were good （r≥0.999 0） between peak area and mass concentration in the ranges of 0.984-49.20， 0.994-49.70， 1.012-50.60， 1.032-51.60， 1.004-50.20， 1.016-50.80 µg·L^-1， respectively. The average recoveries of these six analytes were 87.2%-94.2% with relative standard deviation （RSD）<4.0%. Their MOE values were >10 000. Conclusion:The UPLC-MS/MS established in this study is stable and feasible， which can provide scientific basis for the quality control and safety evaluation of hepatotoxic pyrrolizidine alkaloids in Verbenae Herba.

Objective: To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC). Methods: DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 Results: We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders. Conclusion In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.
Adult ; Aged ; Cancer Vaccines/therapeutic use* ; China ; Dendritic Cells/immunology* ; Female ; Humans ; Immunotherapy/methods* ; Injections, Intradermal ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/therapy* ; Nasopharyngeal Neoplasms/therapy* ; T-Lymphocytes, Cytotoxic/immunology* ; Viral Matrix Proteins/therapeutic use* ; Young Adult

Objective:To investigate the effect of MCC950 (a NLRP3 inflammasome inhibitor) on cognitive impairment in mice with radiation-induced inflammatory brain injury.Methods:Mice were divided into normal (NS) group, whole body irradiation (IR) group and MCC950 intervention post irradiation (IR+ MCC950) group according to the random number table method, with 15 mice in each group. The mice in IR group and IR+ MCC950 group were irradiated with a single dose of 4.0 Gy. The radiation source was 137Cs and the dose rate was 1.118 Gy/min. The mice in NS group were not irradiated. Mice in IR+ MCC950 group were injected intraperitoneally with MCC950 once a day (10 mg/kg each time) from 3 weeks after irradiation. Behavioral tests such as new and old things recognition experiment and social cognition experiment were used to detect the cognitive function of mice. Immunohistochemistry was used to detect the expression of NeuN protein in CA3 area of mouse hippocampus. PCR and Western blot were used to detect the expression of NLRP3 inflammatory body related protein. Results:Compared with NS group, the short-term and long-term recognition index of new and old things in the IR group decreased significantly ( t=4.321, 5.473, P<0.01), and the social cognitive recognition index of the IR group also decreased significantly ( t=2.097, P<0.05). MCC950 treatment reversed the above changes (short-term and long-term new and old thing recognition test: t=5.860, 4.598, P<0.05; new and old position recognition test: t=3.040, P<0.05; social cognition test: t=4.021, P<0.01). The expression of NLRP3, Caspase-1, IL-1 β and IL-18 in mice hippocampus of the IR group was significantly higher than that of the control group ( t=2.699, 8.515, 3.340, 3.950, P<0.05). Compared with NS mice, radiation significantly increased the expressions of Bax, Caspase-3 and PARP1 in hippocampus ( t=3.887, 2.742, 3.287, P<0.05), while MCC950 significantly decreased the expressions of Bax, Caspase-3 and PARP1( t=2.852, 4.090, 9.614, P<0.05). Conclusions:NLRP3 inflammasome inhibitor MCC950 could alleviate radiation-induced cognitive impairment, which may be due to the inhibition of hippocampal inflammatory and neuronal death.

Dental implants have become the main choice for patients to fill in their missing teeth. A precise placement is the basis for a functional and aesthetic restoration. A digital surgical guide is a carrier that transfers the preoperative plan of dental implants to the actual surgery. This paper provides some references that can help clinicians improve the accuracy of implant surgery by stating the development, classification, advantages and disadvantages, and factors that affect the accuracy of digital guides.
Computer-Aided Design ; Dental Implantation, Endosseous ; Dental Implants ; Esthetics, Dental ; Humans ; Imaging, Three-Dimensional ; Patient Care Planning ; Surgery, Computer-Assisted

Objective: To investigate the feasibility of parameter-optimized magnetic resonance imaging (MRI) as the first choice for imaging examination in patients with acute ischemic stroke (AIS), and to assess the effects of quality improvement (QI) measures on shortening the door-to-needle time (DNT). Methods: A retrospective case-control study was conducted. A total of 69 AIS patients hospitalized at the Department of Neurology of the People's Hospital of Wuzhou from August 2015 to July 2018 were enrolled in the study, and the head MRI was used as the first choice for imaging examination. All patients received the intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). Patients with AIS undergoing intravenous thrombolysis from August 2015 to March 2017 were included in the control group, and those receiving intravenous thrombolysis after QI measures from April 2017 to July 2018 were included in the experimental group. QI included informing the stroke team in advance by emergency physicians, treatment process changing from serial procedure to the parallel one, optimization of MRI scanning parameters, and use of rapid test instruments. The MRI scanning time was compared between the two groups. The DNT of the two groups was compared, and paired-samples t test was used. The proportion of patients who underwent MRI scan and DNT<60 min was compared between the two groups, and the χ² test was used. Results: Compared with the control group, the proportion of patients undergoing MRI scan in the experimental group was increased (82% vs 58%, χ²=4.58, P=0.032); MRI scanning time was shortened (4 min 37 s vs 10 min 21 s); DNT (min) was shortened (59.32±10.19 vs 93.48±24.81, t=7.189, P<0.01); and the proportion of patients with DNT<60 min was significantly increased (68% vs 6%, χ²=27.190, P<0.01). Conclusion Parameter-optimized MRI as the first choice for imaging examination in AIS patients with the onset time <4.5 h was feasible, and the DNT was significantly shortened by QI measures.

BACKGROUND: Alcohol consumption has been observed to be a contributing factor in liver damage. However, very few studies have tried to decipher the correlation between patients with liver disease and alcohol consumption. Therefore, this study was planned to determine the prevalence of alcohol consumption among patients with liver disease, and to evaluate the risk factors, liver diseases, and chronic medical conditions associated with alcohol drinking. METHODS: A cross-sectional study was conducted among patients with liver disease in 30 provinces, autonomous regions, and municipalities across China. All participants answered the questionnaire, which led to the calculation of Alcohol Use Disorders Inventory Test (AUDIT) score for each patient. Based on this score, low-risk drinkers, hazardous drinkers, and harmful drinkers were defined as having AUDIT score of <8, between 8 and 15, and ≥16, respectively. RESULTS: A total of 1489 participants completed the questionnaire. Based on this information, 900 (60.44%) participants were classified as alcohol drinkers. Among these, 8.66% were ex-drinkers, 22.10% were low-risk drinkers, 17.13% were hazardous drinkers, and 12.56% were harmful drinkers. Further investigation of the association between alcohol consumption and other baseline characteristics of patients with liver disease revealed that usually men <40 years old, participants having higher family annual income, having college degree or higher education, living alone, having higher body mass index (BMI), current smokers, and ex-smokers had significant association with higher risk of alcohol consumption. In addition, among the 18.07% of the participants with cirrhosis, it was observed that risk of cirrhosis increased with higher alcohol consumption. Furthermore, harmful drinkers showed greater odds of hypertension and heart diseases, while hazardous drinkers and harmful drinkers, both had greater odds of hyperlipidemia. CONCLUSIONS Overall our analyses indicated that among the patients with liver disease in China, there was high rate of alcohol consumption and dependence. Alcohol consumption usually associated with men <40 years old, higher family income, education level, living alone, high BMI, and smoking. Increased alcohol consumption not only increased the risk of cirrhosis, but also enhanced the risk of hypertension, heart diseases, and hyperlipidemia.
Adult ; Aged ; Alcohol Drinking ; adverse effects ; Alcoholism ; etiology ; Cross-Sectional Studies ; Female ; Humans ; Liver Diseases ; etiology ; Male ; Middle Aged ; Smoking ; adverse effects

Objective To evaluate the efficacy and safety of Qianggu capsule and calcium drugs for osteoporosis and to provide reference to choose drug for patients with osteoporosis in clinic. Methods Databases including PubMed, Embase, The Cochrane Library, CNKI, WanFang Data, VIP and SinoMed were searched to collect randomized controlled trials (RCTs) of Qianggu capsule and calcium supplements for osteoporosis from inception to the 31th of January 2017. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of included studies. Meta-analysis was performed using RevMan 5.2 software. Results A total of 8 RCTs were included, which involved 594 patients. The results of meta-analysis showed that the effective rate of the Qianggu capsule group was significantly superior to that of the calcium group [RR (95％ CI) was 1.14 (1.06-1.24)]. The bone mineral density (BMD) at lumbar vertebra and femoral intertrochanter of the Qianggu capsule group were statistically higher than those of the calcium group after three months'treatment [MD (95％ CI):0.10 (0.08-0.12), 0.09 (0.06-0.12)]. The bone mineral density (BMD) at lumbar vertebra, femoral neck, ward triangle and femoral intertrochanter of the Qianggu capsule group were statistically higher than those of the calcium group after six months' treatment [SMD (95％ CI): 0.26 (0.03-0.49), 0.56 (0.32-0.80), 0.64 (0.38-0.91); MD (95％ CI): 0.03 (0.02-0.04)]. The incidence of adverse events of the Qianggu capsule group was statistically higher than that of the calcium group [OR (95％ CI) was 2.03 (1.08-3.82)]. Conclusions Comparing to the calcium related drugs, the Qianggu capsule showed a better effect, and could effectively increase the bone mineral density, but the adverse events should be surveillanced.

Objective To investigate effects analysis of joint function and MMP-7 and MMP-9 measurement after synovial ar-throscopic debridement for knee synovitis.Methods 72 patients with knee synovitis method based on a random draw were e-qually divided into the treatment group and the control group,the control group were given the traditional synovial planing surgery.The treatment group were given the arthroscopic debridement synovium.Results After treatment,the response rates in the treatment group and the control group were 97.2% and 80.6% respectively.The response rate of the treatment group were significantly better than the control group.The difference was statistically significant (P <0.05).The postopera-tive Lysholm scores were increased significantly,while the pain scores were significantly reduced,and the postoperative Ly-sholm score and pain scores difference compared between the two groups were also statistically significant.The difference was statistically significant (P <0.05).The postoperative synovial tissue MMP-7 and MMP-9 expression rates were in the two groups significantly lower.The difference was statistically significant (P <0.05),while the postoperative MMP-7 and MMP-9 expression rates of the treatment group were ignificantly lower than the control group (P <0.05).Conclusion Syn-ovial arthroscopic debridement for knee synovitis can relieve pain and improve knee function,reduce the expression of MMP-7 and MMP-9,thereby enhance the overall efficacy of the treatment.