Objective:To reveal the action mechanism and efficacy of electroacupuncture (EA) plus external application of Wei Ling Xian (Radix Clematidis) extract in treating knee osteoarthritis (KOA), for providing theoretical evidence and novel plan for the treatment of KOA.Methods:Totally 284 inpatients were divided into an EA group and an observation group by the random number table, 142 cases in each group. The EA group was intervened by EA, ultrashort waves, and oral administration of Glucosamine Hydrochloride capsules; while the observation group was by external application of Wei Ling Xian (Radix Clematidis) extract at topical area in addition to the treatment given to the EA group. The intervention lasted 14 d in both groups. X-ray examination of knee joint was ordered before and after treatment, as well as the detection of positive expression of matrix metalloproteinase-1 (MMP-1) in cartilage of knee joint, hyaluronic acid (HA) and interleukin-1β (IL-1β) in the inflammatory effusion; the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and visual analogue scale (VAS) were adopted to evaluate the clinical efficacy.Results:In the observation group, the X-ray examination result of knee joint was significantly improved, the positive expressions of MMP-1 and IL-1β content were significantly decreased, the level of HA was increased, WOMAC and VAS scores dropped, and the total effective rate was 91.5%, which were significantly different from those in the EA group (P<0.05).Conclusion:EA plus external application of Wei Ling Xian (Radix Clematidis) extract can produce a more significant efficacy in treating KOA compared to ordinary EA treatment.

To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.
Adolescent ; Adult ; Anticonvulsants ; blood ; pharmacokinetics ; therapeutic use ; Carbamazepine ; blood ; pharmacokinetics ; therapeutic use ; Drug Interactions ; Drug Therapy, Combination ; Epilepsy ; blood ; drug therapy ; Fatty Acids, Monounsaturated ; blood ; Female ; Humans ; Male ; Valproic Acid ; blood ; pharmacokinetics ; therapeutic use ; Young Adult

BACKGROUNDIn tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model.

METHODS(99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity.

RESULTS(99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01).

CONCLUSIONThis study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.

Animals ; Annexin A5 ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Apoptosis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Histidine ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Mice ; Organotechnetium Compounds ; Paclitaxel ; therapeutic use ; Radiopharmaceuticals

Objective To report our experiences in the treatment of recurrent intracranial aneurysms with re-coiling or covered stents.Methods A total of 291 patients with 305 intracranial aneurysms were treated with detachable coils.and 41(28.9%)of 142 patients with aneurysms in the intemal carotid artery had a recurrent aneurysm during the follow-up period.For this study,31 recurrent aneurysms in 31 patients who had angiograms within 6 months following retreatment with detachable coils(group A,n=20)or covered stents(group B.n=11)were analysed.Aneurysms were categorised as complete or incomplete occlusion via angiographic assessment and graded as full recovery,improvement,no change or deterioration via clinical assessment.Data regarding technical success,initial and final angiographic results,final clinical outcome were collected and analysed postoperatively.Results Coil embolisation and covered stent placement.were technically successful in all recurrent aneurysms.The initial angiographic results showed complete occlusion in 11 patients(55%)in group A and in eight(72.7%)in group B(P=0.452),and the final angiographic results exhibited complete occlusion in 10 patients(50%)in group A and in 11(100%)in group B(P=0.005).There were no significant differences in technique success or final clinical outcome between the two groups.Conclusions Recurrent aneurysms after coiling can be successfully treated and occluded with re-coiling or covered stent placement.However,covered stents seem to be more effective than re-coiling with regard to complete occlusion of recurrent aneurysms.

OBJECTIVETo investigate the relationship between haplotypes of multilocus markers and ankylosing spondylitis (AS).

METHODSFive families with AS were recruited from Shanghai area. Eleven microsatellite markers around D6S276 were analyzed by Linkage package and by Cyrillic package.

RESULTSFine linkage analysis showed the significant Lod score values with D6S276 was 3.8821, Lod score values with D6S1691 and D6S1618 near D6S276 were larger than 1.5. The crossover value in 5 pedigrees was 14%. The haplotype analysis showed that the regions between D6S1691 and D6S1618 were associated with AS.

CONCLUSIONThe regions of D6S1691-D6S276-D6S1618 may harbor a susceptible gene of AS. The specific haplotypes of different pedigrees may play an important role in the presymptomatic diagnosis for AS.

Female ; Haplotypes ; genetics ; Humans ; Linkage Disequilibrium ; genetics ; Male ; Pedigree ; Spondylitis, Ankylosing ; genetics

OBJECTIVETo observe the changes in the expressions of STAT3 and NF-KB in PC-3 cells after IL-6 stimulation and to verify the effects of the NF-KB inhibitor caffeic acid phenethyl ester (CAPE) on the expressions of p-STAT3 and IL-6 in the PC-3 prostate cancer cell line.

METHODSPC-3 prostate cancer cells were treated with IL-6 at 20 ng/ml for 5, 10, 20, 30 and 45 min. The protein and mRNA expressions of STAT3 and NF-kappaB were measured by Western blot and real time PCR, respectively, and the cell cycle was detected by flow cytometry. The PC-3 cells were exposed to TNF-alpha or TNF-alpha + CAPE, followed by determination of the IL-6 expression in the supernatant of the cells by ELISA and the expression of p-STAT3 by Western blot.

RESULTSAfter IL-6 stimulation, both the expression of p-STAT3 protein and the proliferation index of the PC-3 cells were significantly increased, and so were the expressions of IL-6 and p-STAT3 protein in the supernatant after TNF-alpha treatment (P < 0.05). TNF-alpha + CAPE induced statistically lower expressions of IL-6 and p-STAT3 than TNF-alpha alone (P < 0.05).

CONCLUSIONCAPE can inhibit IL-6 secretion induced by TNF-alpha in PC-3 cells and thus suppress STAT3 translocation. Therefore, by inhibiting the expression of NF-kappaB and affecting STAT3 and other related cell signaling pathways, CAPE may become a new therapeutic option for prostate cancer.

Caffeic Acids ; pharmacology ; Cell Line, Tumor ; Humans ; Interleukin-6 ; metabolism ; pharmacology ; Male ; NF-kappa B ; antagonists & inhibitors ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology ; Prostatic Neoplasms ; metabolism ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology

Objective To understand the disease spectrum of prehospital emergency patients in Beijing, so as to provide basis for rational allocation of prehospital emergency care resources and for improvement of prehospital emergency care. Methods Emergency dispatch database from 120 dispatching command system of Beijing Emergency Medical Center to was used study the disease spectrum of 120 prehospital emergency patients from 2013 to 2017 in Beijing, and were analyzed the differences of disease spectrum among patients of different years, genders and ages, and the time distribution of different diseases. Results From 2013 to 2017 in Beijing, 1 643 375 patients used 120 prehospital emergency care. The top 3 diseases of the disease spectrum were: injury and poisoning (29.63%), diseases of the circulatory system (18.37%), and diseases of the nervous system (15.80%). The sorting of diseases remained unchanged during the 5 years. The disease spectrums were different among different age groups and gender groups. The calls in spring, summer, autumn and winter accounted for 25.23%, 24.97%, 25.05% and 24.75% respectively. Most calls were made from 08 ∶〗00 to 09 ∶〗59 (12.41%), 12 ∶〗00 to 13 ∶〗59 (10.05%), and 14 ∶〗00 to 15 ∶〗59 (9.91%) during a day. The peak months and hours of different diseases were different. Conclusions The demand for prehospital emergency care has been increasing in Beijing in recent years. It is important to strengthen the prevention of injuries among all ages, especially male, and to improve the prevention and response capacity for acute attack of chronic diseases among older people. Prehospital emergency care resources should be rationally allocated according to the peak months and hours of calls.

OBJECTIVETo investigate the impact of cytochrome P450 (CYP) 2C19 681G > A polymorphism on long-term prognosis of clopidogrel-treated Chinese patients after percutaneous coronary intervention (PCI).

METHODSBetween January 1, 2009 and August 31,2009, 267 patients with coronary heart disease who received PCI and treated with clopidogrel for 12 months were enrolled. CYP2C19 * 2 was detected by MALDI-TOF MS and patients were grouped into CYP2C19 * 1/ * 1 (n = 130) and CYP2C19 * 2 carriers group (n = 137). Follow-up was 12 months. The primary endpoint was angina recurrence, urgent coronary revascularization, acute myocardial infarction, stent thrombosis, death and the combined end points.

RESULTSBaseline data were similar between two groups (P > 0.05). Urgent coronary revascularization and the combined end points occurred more frequently in CYP2C19 * 2 carriers than in CYP2C19 * 1/* 1 patients (7.3% vs. 1.5% and 8.0% vs. 2.3% respectively, all P < 0.05). But incidence of angina recurrence, acute myocardial infarction, stent thrombosis and death was similar between two groups (all P > 0.05). Hazard risk of 1 year cumulative survival of CYP2C19 * 2 carriers group was significantly higher than CYP2C19 * 1/ * 1 group after PCI ( HR = 3.59, 95% CI: 1.02 - 12.87, P < 0.05).

CONCLUSIONCYP2C19 681G > A polymorphism is a determinant of prognosis in coronary heart disease patients receiving chronic clopidogrel treatment after PCI.

Aged ; Angioplasty, Balloon, Coronary ; Aryl Hydrocarbon Hydroxylases ; genetics ; Coronary Disease ; diagnosis ; drug therapy ; genetics ; Cytochrome P-450 CYP2C19 ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymorphism, Single Nucleotide ; Prognosis ; Ticlopidine ; analogs & derivatives ; therapeutic use

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.
Humans ; Irinotecan ; Colorectal Neoplasms/genetics* ; Resveratrol ; Molecular Docking Simulation ; ErbB Receptors/genetics*

Objective To analyze the characteristics of imported malaria epidemic from overseas in Wuhan, to explore the management mechanism of on-site cases, and to accumulate experience for the treatment of imported malaria in large cities after malaria elimination. Methods The epidemiological data on imported malaria from abroad during the period of malaria elimination (2010-2019) in Wuhan were collected. The gender, age and severe illness-related factors of the cases were analyzed. Based on the characteristics of the epidemic and the current situation of prevention and control, the content and experience of the “Municipal-District 24-7” case mechanism were discussed. Results The medical resources in Wuhan were the best in the central region, resulting in a large number of imported malaria cases, with a total of 474 cases reported from 2010 to 2019 (40.79% of the total number of cases in Hubei Province), including 359 cases of falciparum malaria, 36 severe cases and one death (the death rate was 0.28%). The patients were mainly young and middle-aged men aged 20 to 49 years old (97.26%). There were many referral cases (40.30%), and there was no seasonal clustering of cases reported. The undiagnosed proportion at the first visit was 44.85%, and the time of attack-diagnosis was 4 days or more in 61.00% of cases. The occurrence of severe cases was related to unconfirmed diagnosis at the first visit (χ²=35.46, P<0.001) and attack-diagnosis time (Z=-6.49, P<0.001). Conclusion Imported malaria occurs frequently in Wuhan, mainly falciparum malaria. However, “Municipal-District 24-7” case mechanism has effectively curbed the occurrence of severe and death cases and provided valuable experience for case management in similar cities in China.