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Objective@#This study uses structural magnetic resonance imaging to explore changes in the cerebellar lobules in patients with autism spectrum disorder (ASD) and further analyze the correlation between cerebellar structural changes and clinical symptoms of ASD. @*Methods@#A total of 75 patients with ASD and 97 typically developing (TD) subjects from Autism Brain Imaging Data Exchange dataset were recruited. We adopted an advanced automatic cerebellar lobule segmentation technique called CEREbellum Segmentation to segment each cerebellar hemisphere into 12 lobules. Normalized cortical thickness of each lobule was recorded, and group differences in the cortical measures were evaluated. Correlation analysis was also performed between the normalized cortical thickness and the score of Autism Diagnostic Interview-Revised. @*Results@#Results from analysis of variance showed that the normalized cortical thickness of the ASD group differed significantly from that of the TD group; specifically, the ASD group had lower normalized cortical thickness than the TD group. Post-hoc analysis revealed that the differences were more predominant in the left lobule VI, left lobule Crus I and left lobule X, and in the right lobule VI and right lobule Crus I. Lowered normalized cortical thickness in the left lobule Crus I in the ASD patients correlated positively with the abnormality of development evident at or before 36 months subscore. @*Conclusion@#These results suggest abnormal development of cerebellar lobule structures in ASD patients, and such abnormality might significantly influence the pathogenesis of ASD. These findings provide new insights into the neural mechanisms of ASD, which may be clinically relevant to ASD diagnosis.
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Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention (EPR) effect without introduction of inactive substances, and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4 (PAD4) molecular inhibitor, ZD-E-1M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps (NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pH-responsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed, while IFN-γ and TNF-α as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.
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OBJECTIVE：To identify Amomum villosum from different habitats and its adulterants. METHODS ：Through the identification methods of microscopic characteristics ，microscopic characteristics maps of 9 batches of A. villosum from genuine producing areas ，domestic commercially available A. villosum and its adulterants were obtained. The feature maps were extracted digitally and analyzed by SPSS 21.0 software. RESULTS ：Commercially available A. villosum was mainly from Guangdong ， Guangxi，Yunnan and Fujian ；the collected adulterants of A. villosum included A. villosum Lour. var. xanthioides T.L.Wu et Senjen ， A. aurantiacum H. T. Tsai et S. W. Zhao and other A. species from Yunnan Xishuangbanna ， Laos and Myanmar. Under the microscope，it was observed that microscopic characteristics of surface （such as exocarp color ，prickle，non-glandular hairs ， endocarp color ，endocarp oil chamber ） of A. villosum from different habitats and its adulterants were different. There was statistically significant difference in fruit width values and endocarp oil point diameter among all samples （P＜0.05）. CONCLUSIONS：The microscopic characteristics maps of A. villosum from different habitats and its adulterants by the microscopic characteristics identification methods will make up for the deficiency of traditional experience identification. The quantitative analysis of micro-property and the establishment of micro-property database of A. villosum can provide reference for the property identification and quality control of this medicinal material.
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Antibody-drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody-drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers.
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Objective To investigate the effects of different doses of oxaliplatin (L-OHP) chemotherapy regimen for treatment of colorectal cancer and its influence on the adverse reactions in the nervous system.Methods A total of 92 cases of colorectal cancer patients in Wuhan Wuchang Hospital from August 2013 to April 2016 were selected as the research objects, which were randomly divided into the observation group (46 cases) and the control group (46 cases) according to the random lottery envelopes. All the patients were given FOLFOX chemotherapy. The observation group was treated with small dose L-OHP chemotherapy(60 mg/m2),the control group was treated with routine dose of L-OHP chemotherapy(120 mg/m2), and the efficacies were evaluated after 3 cycles. Results All the patients completed chemotherapy. The observation group included 26 cases of complete remission(CR),11 cases of partial remission(PR),5 cases of stable disease (SD), 4 cases of progression of disease (PD). The control group included 28 cases of CR, 10 cases of PR, 3 cases of SD, 5 cases of PD. Overall response rate (ORR) in the observation group and the control group were 80.4 % (37/46) and 82.6 % (38/46) respectively, and there was no significant difference between the two groups (χ 2= 0.072, P > 0.05). Nervous system adverse reactions included 6 cases of gradeⅠ, 3 cases of grade Ⅱ, 1 case of grade Ⅲ in the observation group, and 12 cases of grade Ⅰ, 6 cases of gradeⅡ,4 cases of gradeⅢin the control group.The incidence rate in the observation group was lower than that in the control group [21.7 % (10/46) vs. 47.8 % (22/46), χ2= 6.900, P < 0.05]. Up to November 2017, PD and overall survival time in the observation group were longer than those in the control group [(19 ±4)months vs. (16±4) months, t= 4.314, P< 0.05; (24±4) months vs. (20±5) months, t = 4.170, P < 0.05]. Conclusion The low dose L-OHP chemotherapy regimen has a favorable effect in patients with colorectal cancer, and it can reduce the adverse reactions in the nervous system and prolong the survival time of patients.
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Objective To investigate the value of microwave ablation in the treatment of hepatocellular carcinoma in the caudate lobe.Methods We retrospectively analyzed the data of patients with hepatocellular carcinoma in the caudate lobe treated primarily by microwave ablation from January 2011 to May 2016 in our department,and explore the safety,efficacy of microwave ablation (MWA).Results The 11 patients had been treated with microwave ablation procedure in 13 lesions,through caudate lobe epigastric puncture in 9 cases and intercostal puncture in 2 cases.A total of 2 cases did not reach the technical success due to one case treated by radiation therapy,and the other treated by repeated MWA.However,the repeated MWA of that patient failed to reach the technical success.And the effective rate of treatment was 81.8％ (9/11).Following up to October 2016,the average follow-up time was (31.5±15.4) months.There were 1 patient with extrahepatic metastasis and 4 cases of patients with intrahepatic distant recurrence,among which 3 cases underwent MWA treatment again and 1 case underwent radiotherapy.Conclusion Microwave ablation is a safe and effective therapy option for the Caudate Lobe tumor.
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Objective To evaluate the curative effect of microwave ablation (MWA) for solitary hepatocellular carcinoma (HCC) sized less than 5 cm,and to discuss the prognosis and its influence factors.Methods The clinical data of 603 HCC patients,who were admitted to authors' hospital during the period from 2011 to 2013 to receive MWA,were retrospectively analyzed.The patients were followed up till March 2016.Results According to the inclusion criteria,a total of 603 patients were enrolled in this study.Complete ablation of HCC lesions was obtained in 5.8％ of patients (35/603).No statistically significant difference in complete ablation rate existed between each other among groups of different tumor diameter (P=0.056).The incidence of severe complications was 1.7％ (10/603).The median survival time was (59.6±1.9)months,while the 1-,2-and 3-year overall survival rates were 94.7％,81.9％ and 71.8％ respectively.In terms of overall survival rate,no statistically significant difference existed between groups of different age as well as between groups of different tumor diameter (P=0.225 and P=0.777 respectively),but statistically significant difference existed between groups of different sex as well as between groups of different recurrence interval (P=0.029 and P＜0.001 respectively).Univariate and multivariate analysis showed that gender,preoperative albumin level and recurrence interval were the factors influencing overall survival rate (P=0.035,P=0.006 and P＜0.001 respectively).Conclusion For the treatment of solitary HCC sized less than 5 cm,MWA has reliable curative effect,it is a safe and minimally-invasive therapy for HCC.The overall survival rate between patients with different age or between patients with different HCC size is not obviously different.The gender,preoperative albumin level and recurrence interval are independent factors that affect the overall survival rate.
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Vaginal delivery system has a unique therapeutic advantage. In recent years, the rapid development of dosage forms shows a good prospect of development. The related literatures at home and abroad in recent years were analyzed and summarized. The research progress in the drug absorption model of various vaginal administrations was reviewed. The review provided reference for the research of new drug preparations and drug absorption mechanisms of vaginal administration.
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Nevirapine ( NVP) is the first-generation non-nucleoside reverse transcriptase inhibitor, which is a front-line drug for the treatment of AIDS and the prevention of mother-to-child transmission of HIV-1. NVP is with poor solubility and low bioavailability. With the development of new dosage forms, such as solid dispersion, self-emulsifying, microparticles, micelles, sustained-release tab-lets and floating microspheres, the bioavailability of NVP can be increased and the adverse reactions can be decreased. Research pro-gress in the new dosage forms of NVP at home and abroad was reviewed through searching literatures in order to provide basis for the development of new dosage forms of NVP.
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Objective To investigate the effect of the optimal prescription of huiru yizeng on rats with hyperplasia of mammary gland and hyperprolactinemia. Methods Fifty-six female Wistar rats were randomly divided into 7 groups (n=8), including normal control group, model control group, sodium chloride group, bromocriptin group, rupi sanjie group, the original prescription group and optimizing prescription group. Rat model of mammary gland hyperplasia with hyperprolactinemia was replicated in 6 groups but not the normal control group. The successfully established experimental rats were given corresponding drugs by intragastric gavage. After 30 days, the levels of the estradiol, progesterone, and prolactin were detected, and the pathomrphology of glandular tissue was observed. Results Prolactin levels of model control group, the original prescription group and optimize prescription group were (69.47 ±6.08), (53.13 ±10.59), and (28.41 ±6.37) pg·mL-1, respectively . Compared with that in the model control group, the contents of prolactin in both the optimal prescription group and the original prescription group were reduced, but the optimal prescription group was better (P<0. 01). In the original prescription group, the lobules of mammary gland showed a few of hyperplasia, the individual alveoli and duct showed a slight hyperplasia, and a small amount of secretions was found in the duct. The degree of the hyperplasia was alleviated in the optimal prescription group similar to that observed in the normal control group, which showed that there was no hyperplasia in the lobules of mammary gland or no secretions in the duct. Conclusion The therapeutic effects of the optimal prescription are much better than the original prescription, which can effectively lower the level of prolactin, adjust the balance among the prolactin , estrogen and progesterone, and alleviate the pathological hyperplasia of mammary glands in the model rats.
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Objective@#To investigate the efficacy of microwave ablation in the treatment of hepatocellular carcinoma (HCC) within the Milan criteria and to investigate the differences in clinical efficacy of microwave ablation in tumors with different sizes.@*Methods@#A retrospective analysis was performed on the clinical data of the patients with HCC within the Milan criteria who received microwave ablation in our hospital from January 2011 to January 2013. The complete ablation rate, incidence rate of major complications, recurrence rate, and overall survival rate were analyzed and the treatment outcomes were compared between two groups with different tumors sizes. The patients were followed up for 3.4-61.8 months. The Kaplan-Meier method was used to calculate overall survival rate, local recurrence rate, and distant recurrence rate. Comparison of rates between groups was made by the chi-square test and comparison of survival rates between groups was made by the log-rank test.@*Results@#A total of 696 patients with HCC within the Milan criteria involving 801 tumors were included in this study. The complete ablation rate was 93.8% (653/696) and the incidence rate of major complications was 1.7% (12/696). The median survival time was 59.6 months and the 1-, 2-, and 3-year overall survival rates were 94.8%, 82.2%, and 71.7%, respectively. The local recurrence rate was 13.4% (93/696) and the rate of intrahepatic distant metastasis was 40.1% (279/696). The overall intrahepatic recurrence rate was 48.1% (335/696), and the 1-, 2-, and 3-year recurrence rates were 22.9%, 38.4%, and 46.8%, respectively. There were no significant differences in complete ablation rate, incidence rate of major complications, and overall survival rate between the two groups with different tumor sizes (diameters≤3 cm and 3-5 cm) (P = 0.12; P = 0.61; P = 0.61).@*Conclusion@#Microwave ablation is a safe and effective treatment modality for HCC within the Milan criteria. And there are no significant differences in safety, effectiveness, and long-term efficacy of microwave ablation between the two groups with different tumor sizes (diameters ≤3 cm and 3-5 cm). However, if the operator’s experience is not rich and cannot accurately use conformal ablation and make an individualized treatment, the tumors with a diameter of 3-5 cm should be carefully treated using microwave ablation to avoid residual tumor after treatment.
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Pulmonary drug delivery has become a research focus in recent years, while the action between particles and pulmonary macrophages after particles transportation to lung tissue was paid little attention. Therapeutic efficacy can be enhanced by regulating the particles uptake action of pulmonary macrophages according to different diseases. Referring to a lot of articles, the relationship between common diseases and macrophages was reviewed and the influencing factors in the particles uptake of alveolar macrophages were sum-marized. The review laid foundation for the development of preparations and clinical application of pulmonary drug delivery systems.
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<p><b>OBJECTIVE</b>To compare the efficacy differences between ginger-separated moxibustion atpoints combined withformula andformula alone on patients with decreased ovarian reserve function.</p><p><b>METHODS</b>Fifty patients of decreased ovarian reserve function were randomly divided into an observation group and a control group, 25 cases in each one. The patients in the observation group were treated with ginger-separated moxibustion atpoints combined withformula; the moxibustion was given for 1.5 h, once every seven days, and no treatment was given during menstrual period. The patients in the control group were treated withformula. One-month treatment was taken as one treatment course, and totally three courses were given. The change of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E), anti-mullerian hormone (AMH), antral follicle count (AFC), peak systolic velocity (PSV), resistance index (RI) were observed before and after treatment in the two groups.</p><p><b>RESULTS</b>After treatment, the FSH, FSH/LH and RI were significantly lowered, but the E, AFC, PSV were significantly increased in the two groups (all<0.05); the FSH, FSH/LH and Ein the observation group were lower and AFC was higher than those in the control group (all<0.05).</p><p><b>CONCLUSION</b>The ginger-separated moxibustion atpoints combined withformula are superior toformula alone in improving ovarian reserve function.</p>
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Objective To identify the types,frequency and risk factors of major complications using microwave ablation (MWA) to treat liver malignancies in a single center.Methods Using the electronic medical record system,patients with liver cancer who were treated with MWA from January 2010 to November 2015 were retrospectively studied,and the risk factors of severe complications were analyzed.Results Of the 7 403 patients who were treated with MWA (12 558 ablations).96 cases experienced severe complications (1.3％) and 5 patients died (0.07％).The complications included liver abscess (n ＝ 34,0.46％),pleural effusion (n ＝ 20,0.27％),bile duct injury (n ＝ 15,0.20％),hemorrhage (n ＝ 6,0.08％),liver failure (n ＝ 6,0.08％),extrahepa-tic organ injuries (n ＝ 5,0.07％),cancerous cells implantation of abdominal walls (n ＝ 2),cardiac arrest (n ＝ 1),vascular thrombosis (n ＝ 1),renal insufficiency (n ＝ 1),and patients with other associated diseases which developed after the MWA therapy (n ＝2).Metastatic liver cancer and earlier treatment of MWA sessions were associated with a higher major complication rate (P ＜ 0.05).Conclnsions MWA is a well-tolerated local treatment for liver cancer,with an acceptably low incidence of severe complications.Liver abscess was the most common postoperative severe complication.The surgeons＇ experience and tumor type were associated with the incidence of severe complications,however,not relavant with the frequency of preoperative ablations.Appropriate measures can be taken to effectively reduce the risk of serious complications.
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As a new design strategy of anticancer drugs,antibody-drug conjugates have become a research hotspot in recent years. In 2013,the successful launch of ado trastuzumab emtansine(Kadcyla)provided a new solution for second-line treatment with trastuzumab-resistant HER2-positive advanced breast cancer patients. Based on its excellent clinical performance and HER2′s overex?pressing in many tumors,Roche further attempts to expand it for the therapy of HER2-positive metastatic breast cancer of each line and neoadjuvant for early breast cancer treatment,as well as applications to gastric cancer and non-small cell lung cancer(NSCLC) treatment. In general,results are mixed. Its position as second-line drugs of is further established,but factors such as tumor heteroge?neity are still a big challenge. This paper reviews the recent progress in these areas after its launch.
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Minimally invasive ablation is one of the most effective therapy methods for liver tumor. Eastern Hepatobiliary Surgery Hospital, Second Military Medical University is responsible for the training of refresher physicians in liver tumor minimally invasive ablation. However, due to the different professional background of the refresher physician, the conventional teaching method is not enough. Through the train-ing of clinical thinking, image reading ability, ultrasound guide operation and the management of intraop-erative and postoperative complications in many aspects targeted teaching, reaching the purpose of training, increasing the experience of popularities of minimally invasive ablation technology, and providing a reference basis for future refresher physician teaching in liver tumor minimally invasive ablation.
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Compared with the traditional anti-tumor therapy,the antibody-based therapeutic strategies have shown consider?ably higher targeting selectivity and lower side effects. Antibody drug conjugates(ADC),combining the advantage of the biological antibodies and small molecule toxins,is regarded as a new way for the future cancer therapy. Maytansines are one of the cytotoxins widely used in ADC and the postmarketing ADC ado-trastuzumab emtansine(Kadcyla,ATE)which use such toxins successfully has expanded the indications from leukemia to other solid tumors. Currently,the clinical research progress in such ADC goes smoothly. This paper reviews the characteristics,metabolic characteristics,preparation of each component and the latest clinical research prog?ress in the maytansine class ADC.
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Objective To synthesize poly asparagine derivatives and to evaluate its safety at the cellular level, which provide research platform for its potential application as drug carrier. Methods Polysuccinimide was synthesized by ther?mal polymerization of L-polyaspartic acid, and the target product of PSI-Phe-EA was obtained by the ring-opening reaction of polysuccinimide using L-phenylalanine methyl ester hydrochloride and ethanol amine. The structure of PSI-Phe-EA were characterized by 1H NMR. The rate of ring-opening of PSI was calculated by internal standard method of 1H NMR. The change of hydrophilicity was studied by the comparison of solubility. The cytotoxicity and morphology modification by PSI-Phe-EA at designate concentrations was investigated by MTT method and inverted microscopy respectively. The effects on cell cycles were analyzed by flow cytometry after propidium iodide (PI) staining. Results 1H NMR results confirmed the structure of PSI-Phe-EA and the ring-openning rate of PSI was 40%. The hydrophilicity of PSI-Phe-EA was greatly in?creased upon ring opening using ethanol amine. MTT test showed that the cell survival rates of NIH 3T3 and HepG2 cells were higher than 80%under the examined concentration (<100 mg/L). Inverted microscopy showed that 50 mg/L of PSI-Phe-EA treatment had no adverse effects on cell morphology. Cell cycle analysis indicated that PSI-Phe-EA treatment had no in?fluence on cell cycles of NIH 3T3 and HepG2 cell lines. Conclusion PSI-Phe-EA showed high hydrophilicity without sig?nificant effects on the cells survival, cells morphology and cell cycles. It is a kind of safe polymer material.
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Aim To investigate the mechanism of the melanoma B16 F10 cells proliferation induced by Lico-chalcone A in vitro. Methods The proliferation of B16 F10 cells induced by Licochalcone A was deter-mined by SRB method. The morphological changes were observed using Giemsa staining under the phase contrast microscope equipped with a digital camera. The melanin level was assessed by colorimetric meth-od. The apoptotic rate was determined by Annexin V-FITC/PI assay. Cell cycle distribution was determined by flow cytometry. The mRNA expression levels of B cell lymphoma/lewkmia-2 ( Bcl-2 ) , Bcl-2 associated X protein ( Bax) , the cell cycle protein CyclinE2 and cyclin-dependent kinase-2 ( CDK2 ) CDK2 were detec-ted using Q-PCR analysis. Results The proliferation of B16 F10 cells treated with Licochalcone A was effec-tively inhibited in a concentration and time-dependent manner. A clear morphological change was observed with the increasing concentration of Licochalcone A in B16F10 cells, the dendrite-like projections changed to the narrowing ball shape, which was associated with the increasing melanin level. The low concentration of Licochalcone A could induce B16F10 differentiation, and the high concentration of Licochalcone A could in-duce B16F10 apoptosis, which was accompanied with the increasing G1 phase in cell cycle. The mRNA ex-pression levels of Bcl-2 /Bax, CyclinE2 and CDK2 were markedly reduced. Conclusion Licochalcone A can effectively inhibit the proliferation of B16 F10 cells, induced cell cycle arrest at G1 phase, and fur-ther induced differentiation and apoptosis.
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Objective To synthesize a new ethynylated open ring derivatives of polyasparamide as functional drug carrier.Methods L-phenylalanine methyl ester hydrochloride was prepared using L-phenylalanine and then was used for ring opening reaction of polysuccinimide.To synthesize the target product of PSI-Phe-OMe-PA, the obtained polyasparamide-g-phenylalanine derivatives ( PSI-Phe-OMe) was further ring opened by propargylamine.The structure of PSI-Phe-OMe-PA was confirmed by 1 H NMR.The biocompatibility of PSI-Phe-OMe-PA was evaluated by MTT method, inverted microscope observation and cell cycles analysis ( propidium iodide staining ) .Results The ring-opening rate of polyasparamide by L-phenylalanine methyl ester and propargylamine was 40%and 100%, respectively.All results of biocompatibility studies indicated that PSI-Phe-OMe-PA may be a good candidate for functional drug carrier.Conclusion Based on the ring-opening capability of amino-group and the specificity of click reaction, L-phenylalanine methyl ester hydrochloride and propargylamine were used successively to react with polyasparamide.PSI-Phe-OMe-PA is a biocompatible functional drug carrier.