Objective:To investigate the efficacy and side effects of concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy.Methods:In the prospective study, 100 patients with stage Ⅲ-Ⅳa locally advanced nasopharyngeal carcinoma (except T 3N 0M 0 stage) who met the inclusion criteria were randomly divided into the experimental and control groups using the random number table method. Patients in both groups were treated with neoadjuvant chemotherapy using TPF (paclitaxel liposome, cisplatin, and 5-fluorouracil) regimen for 2 cycles. At 2 weeks after chemotherapy, concurrent chemoradiotherapy plus nimotuzumab targeted therapy was given in the experimental group, and concurrent chemoradiotherapy was delivered in the control group. The main observation index was the distant metastasis-free survival (DMFS) rate. Log-rank test and multivariate Cox regression analysis were used. Results:The objective remission rate and complete remission rate in the experimental and control groups were 100% vs. 98% ( P=1.000) and 92.0% vs. 80% ( P=0.084). The 3-year DMFS in the experimental and control groups were 91.4 % vs. 76.1 % ( P=0.043). The 3-year progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and overall survival (OS) in two groups were 87.3 % vs. 74.1 % ( P=0.097), 94.5 % vs. 85.6 % ( P=0.227) and 90.5% vs. 85.2% ( P=0.444). Subgroup analysis showed that patients with age<60 years ( HR=0.34, 95% CI=0.12-0.94, P=0.037), neutrophil-to-lymphocyte ratio (NLR)≤4 ( HR=0.34, 95% CI=0.13-0.89, P=0.028) received concurrent chemoradiotherapy plus nimotuzumab obtained better PFS. Multivariate analysis showed that NLR was an independent risk factor for disease progression ( HR=5.94, 95% CI=1.18-29.81, P=0.030) and distant metastasis ( HR=13.76, 95% CI=1.52-124.36, P=0.020). Conclusions:Compared with concurrent chemoradiotherapy alone, concurrent chemoradiotherapy combined with nimotuzumab after neoadjuvant chemotherapy can significantly increase DMFS rate for patients with locally advanced nasopharyngeal carcinoma. The incidence of side effects is similar in two groups. Concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy may be a preferred treatment strategy for locally advanced nasopharyngeal carcinoma.

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.
Humans ; NF-kappa B/metabolism* ; Interleukin-10 ; Nucleus Pulposus/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Aggrecans/metabolism* ; Toll-Like Receptor 4/metabolism* ; RNA, Messenger/metabolism*

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established to investigate the pharmacokinetic behaviors of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone in rat plasma after oral administration of Bufei Huoxue Capsules. After SD rats were administered with Bufei Huoxue Capsules suspension by gavage, blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm). The mobile phase consisted of acetonitrile(A) and water(B) containing 0.1% formic acid in gradient elution. The positive and negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 3.2.8. Psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone were detected in the rat plasma after drug administration, with AUC_(0-t) of(3 357±1 348),(3 555±1 696),(3.03±0.88),(2.21±0.33),(1 787±522),(2 295±539),(5.69±1.41) and(3.40±0.75) μg·L~(-1)·h, and T_(max) of(1.56±0.62),(1.40±0.70),(0.21±0.05),(0.25±0.12),(0.26±0.11),(0.34±0.29),(0.74±0.59), and 0.25 h. The method is proved specific and repeatable and is suitable for the determination of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, pso-ralen, isopsoralen, methylnissolin, and neobavaisoflavone in the rat plasma, which can be applied to pharmacokinetic study.
Animals ; Capsules ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/pharmacokinetics* ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry/methods*

Neurotropin is an extract micromolecule mixture containing many conjugated polysaccarides isolated from the skin or tissues of rabbits which have been inoculated with the living cowpox virus.Neurotropin is widely used in pain treatment and anti-allergy treatment,especially for neuropathic pain,it has a unique effect.Pharmacological effects of neurotropin focused on regulating immune system function,regulating pain signaling,protecting cells and nerves,and suppressing inflammatory reactions.It is widely used in clinical various acute and chronic orthopedic pain diseases,neurological cerebral ischemia,neuralgia and neuroinflammation diseases,dermatological pruritus,allergic diseases.This review focuses on the pharmacological action and clinical application progress of neurotropin.

Objective To explore the value of echocardiography in patients with aortic stenosis who underwent transapical aortic valve implantation (TAAVI).Methods Fifteen high-risk patients with severe aortic stenosis were chosen in the present study,all of which received TAAVI in Fuwai Hospital Chinese Academy of Medical Sciences from June 2014 to March 2015.The left ventricular end-diastolic diameter (LVEDD),left atrial diameter (LAD),left ventricular ejection fraction (LVEF),effective orifice area (EOA),mean aortic pressure gradient (MPG),as well as artificial valve function of patients were measured at different time points (before operation,discharge,1 month and 3-6 months after operation) by echocardiography.The data were analyzed using one-way ANOVA analysis with SPSS software,and multiple comparisons were done using LSD student t test.Results The data from preoperative echocardiography indicated severe aortic stenosis in the 15 patients,with the average level of EOA as (0.55± 0.28) cm2 and MPG as (58.93± 14.96) mmHg (1 mmHg=0.133 kPa).Moderate paravalvular aortic regurgitation was observed in one patients,who was then received a second implantation.There was no significant difference between LVEDD,LAD,and LVEF when the patients were at discharge,1 month and 3-6 months after operation.The prosthetic valves were stable and conformed by echocardiography,while paravalvular leak regurgitation (1-2 mm) was observed in 7 patients.One patient died of other reasons.Compared with preoperative data,the EOA increased while MPG decreased when the patients were at discharge,1 month and 3-6 month after operation (t=6.619,7.357,6.401,all P ＜ 0.001;t=9.523,9.687,5.932,all P ＜ 0.001).Conclusion With careful patient screening and selection,TAAVI can be an effective treatment for high-risk severe aortic stenosis patients,in which echocardiography plays an important role during the surgery and follow up.

Objective To explore the survival time and its influencing factors of patients in Guizhou Province after they received antiretroviral therapy(ART)for treating human immunodeficiency virus (HIV)infection and acquired immunodeficiency syndrome (AIDS).Methods A retrospective cohort analysis was conducted to analyze survival time of AIDS patients who received ART in Guizhou Province in 2005-2016,life table method was used to calculate the survival probability,Cox proportional hazards regression model was used to analyze the influencing factors of survival time.Results A total of 15921 patients were included in the study,the median age at the beginning of therapy was(42.13±14.40)years old,58.61% of patients were married/housemate.The length of ART follow-up was (median[P 25 -P 75 ]:15.96[6.00 - 33.00])months.9.77% of the follow-up cases died,59.29% of the deaths occurred within 12 months of initiation of treatment;survival rates in the first,fifth,and tenth year were 93.00%,82.00%,and 74.00% respectively.Cox proportional hazards regression model analysis showed that fe-male patients were 0.58 times more likely to die than male patients(95% CI :0.49-0.68);the risk of death in-creased with increase of ages;the higher the baseline CD4+ T lymphocyte count,the lower the risk of death;the risk of death in patients without symptoms or signs before therapy was 0.70 times than those with symptoms or signs(95% CI :0.60-0.81).Conclusion The antiviral therapy of AIDS patients in Guizhou Province is generally well,patients with high risk factors for death should be paid high attention,it is suggested that medical level and service quality should be improved when patients are treated.

According to the technology requirements of the fourth national survey of Chinese Materia Medica resources (pilot), suitable investigation method of exploration and suggestions for investigating Chinese Materia Medica resources was proposed based on the type of wetland and artificial water of Hongze Lake region. Environment of Hongze Lake and overview of wetland, present situation of ecology and vegetation and vegetation distribution were analyzed. Establishment of survey plan, selection of sample area and sample square and confirmation of representative water area survey plan were all suggested. The present study provide references for improving Chinese materia medica resources survey around Hongze Lake, and improving the technical specifications. It also provide references for investigating Chinese Materia Medica resources survey on similar ecological environment under the condition of artificial intervention.

The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.
Animals ; Caspase 8 ; biosynthesis ; genetics ; Cell Line ; Cyclin D1 ; biosynthesis ; genetics ; G1 Phase ; physiology ; Histones ; genetics ; metabolism ; Ki-67 Antigen ; biosynthesis ; genetics ; Male ; Mice ; Proliferating Cell Nuclear Antigen ; biosynthesis ; genetics ; Resting Phase, Cell Cycle ; physiology ; Spermatogonia ; cytology ; metabolism ; bcl-2-Associated X Protein ; biosynthesis ; genetics

The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.