Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.
China ; Drugs, Chinese Herbal ; Humans ; Hypertension, Pulmonary/drug therapy* ; Materia Medica ; Medicine, Chinese Traditional

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.
Animals ; Cell Cycle Proteins/genetics* ; Cell Line ; Cell Survival ; Chondroitin Sulfate Proteoglycans/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Gene Expression Regulation ; Gene Knockdown Techniques ; Infertility, Male ; Male ; Meiosis/genetics* ; Mice ; Mice, Knockout ; Mice, Transgenic ; Phosphate-Binding Proteins/genetics* ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics* ; Rad51 Recombinase/genetics* ; Real-Time Polymerase Chain Reaction ; Spermatocytes/metabolism* ; Spermatogenesis/genetics* ; Spermatogonia/metabolism*

OBJECTIVE: To report an overview of bariatric & metabolic surgery performed in 2018 in North China. METHODS: Based on prospective and observational North China Bariatric & Metabolic Surgery Clinical Database(NC-BMD), the study of evaluating the number and the type of bariatric &metabolic surgery procedures was performed in North China. Demographic characteristic, obesityrelated diseases and operational information were also analyzed. RESULTS: In 2018, 17 centers from 7 regions in North China contributed a total of 728 registration data. Valid data were analyzed from 16 centers. The patients' median (minimum, maximum) BMI pre-surgery was 38.4(24.7,95.2). The overall proportion of female patients was 74.7%, and mean±SD age was(32.5±8.29) years, while male patients was 25.3%, and mean±SD age was (32.7±9.90) years. According the data 93.9% laparoscopic sleeve gastrectomy(LSG), 4.4% laparoscopic Roux-en-Y gastric bypass (LRYGB) and 1.7% other operation types. 29.2% of patients had a history of type 2 diabetes, 69.4% had sleep apnea, and 22.6% had polycystic ovary syndrome before operation. CONCLUSION: The establishment of NC-BMD has laid a solid foundation for data registration in North China. Based on current data, LSG is the mainstream of bariatric and metabolic surgery in North China this year.

Adult ; Aged ; Aqueous Humor ; virology ; Female ; Humans ; Immunocompetence ; immunology ; Inflammation ; virology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective To explore the association between unhealthy diets and depression in early pregnancy. Methods 7 976 women in early pregnancy were recruited and analyzed in this study from the Chinese Pregnant Women Cohort Study (CPWCS) from July 25th, 2017 to July 24th, 2018. Differences of baseline characteristics between the two groups were conducted by a chi-square test. The qualitative food frequency questionnaire and the edinburgh postnatal depression scale were used to assess depression status and food intake frequency during the first trimester respectively. Log-binomial regression was used to analyze the relationship between unhealthy diets and depression in early pregnancy. Prevalence ratio (PR) and its 95% confidence interval (95% CI) were calculated. Results Eating regularly (PR=0.45, 95% CI:0.38-0.54，P<0.001) and eating breakfast frequently (PR=0.80, 95% CI:0.72-0.90, P<0.001) were related to the low incidence of depression while frequent consumption of fried food (PR=1.25, 95% CI:1.03-1.53, P=0.027), Western-style fast food (PR=1.36, 95% CI:1.06-1.74, P=0.015) and puffed food (PR=1.37, 95% CI:1.11-1.70, P=0.003) as well as drinking sugar-sweetened beverage (PR=1.37, 95% CI:1.17-1.61, P<0.001),wine (PR=1.60, 95% CI:1.26-2.01, P<0.001) and liqueur (PR=1.26, 95% CI:1.00-1.59, P=0.047) were linked with the high incidence of depression. Conclusions There might be an association between unhealthy diets and depression in early pregnancy. Pregnant women should take the initiative to better understand what are healthy diets and reduce the frequency of unhealthy diets consumption to decrease the incidence of depression during pregnancy.

·AIM:To compare the short-term surgical results of 27-gauge ( 27G ) with 25 - gauge ( 25G ) microincision vitrectomy surgery ( MIVS ) for the treatment of vitreoretinal diseases and evaluate the feasibility, safety and effectiveness of 27G MIVS. · METHODS: Two hundred and seventeen eyes with various vitreoretinal diseases underwent 27G or 25G MIVS from April 2016 to October 2017 and were retrospectively reviewed. One hundred and thirty-five eyes underwent 27G vitrectomy and 82 eyes for 25G vitrectomy. The main outcome measurements of the study included surgical time, intraoperative complications, postoperative ocular inflammation reaction, short-term best corrected visual acuity ( BCVA, LogMAR ) recovery and intraocular pressure fluctuation. ·RESULTS: All surgeries were completed successfully, and no eye in 27G group needed conversion to 25G vitrectomy. The mean surgical times in the 25G group was 56. 4±38. 9 min, which was significant longer than that of 27G group (45. 5 ± 26. 1 min, t= 2. 422, P= 0. 016). However, when comparing the surgical time for each category of disease, there were no significant differences observed (P>0. 05). Within the first week postoperatively, the mean cumulative score of conjunctival congestion, anterior chamber flare and aqueous cell in 25G group were 2.4±1.4, 0.7±1 and 0.5±1, which were higher than those in 27G group (2. 1 ± 1. 6, 0. 3 ± 0. 6, and 0. 2 ± 0. 4), with significant differences (P=0. 038, P=0. 011, P=0. 046 respectively). The improvement of BCVA was-0. 4±0. 9 in 25G group, and -0. 2 ± 0. 9 in the 27G groups respectively (t= -1. 636, P = 0. 103 ). The rate of transient ocular hypotony of the 25G vitrectomy was 19. 5% (16 eyes), which was higher than that of the 27G group without significant difference ( 15. 6% , 21 eyes; χ2= 0. 565, P=0. 452). When the eyes injected with silicone oil were excluded, there was no significant difference in intraocular pressure fluctuation between the 25G group (3. 59±0. 69mmHg) and the 27G group (3. 58±0. 47mmHg;t=0. 007, P=0. 995). ·CONCLUSION: The 27G microincision vitrectomy can be used to treat various vitreoretinal diseases. It is a safe and effective surgical procedure with small incision and mild anterior segment inflammatory reaction.

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

AIM:To compare the clinical effects of 25G+ and 27G+ transconjunctival sutureless vitrectomy in treating idiopathic macular hole.METHODS: We retrospectively reviewed the clinical outcomes of 56 eyes (56 patients) with idiopathic macular hole which were treated with micro-incision vitrectomy from June 2015 to September 2016.Patients were divided into two groups, 28 patients (28 eyes) were treated with 25G+ vitrectomy and the rest (28 eyes) were treated with 27G+ vitrectomy.The operative time and intraoperative complications were recorded and patients were followed up for 3-6mo.During the follow up period, best correct vision acuity (BCVA), intraocular pressure, macular hole healing and postoperative complications were documented and statistically analyzed.RESULTS: BCVA in two groups were significantly improved after surgery(P<0.001) and there was no significant difference between the two groups(P=0.84).No serious complications occurred.No statistically significant difference was found between the two groups in surgical time and healing rate of macular hole (P=0.57, 0.64).The incidence of low intraocular pressure (IOP<10mmHg) in 27G+ group was lower than that in 25G+ group on the first day after surgery(P=0.31).There was no significant difference between preoperative and postoperative intraocular pressure at 1wk after operation in both groups (P=0.72, 0.92).CONCLUSION: Both 25G+ and 27G+ vitrectomy are safe and effective technique in treating idiopathic macular hole.Besides, 27G+ showed better superiority on the maintenance of intraocular pressure and reduce the trauma.

AIM:To evaluate the feasibility and advantages of two-port 27-gauge pars plana vitrectomy for treatment of recurrent retinal detachment in silicone oil dwelling eyes.METHODS:A retrospective study.Two-port 27-gauge pars plana vitrectomy was performed in 7 eyes with recurrent retinal detachment without remove of silicone oil.Proliferative membrane peeling, endolaser treatment, and drainage of subretinal fluid were performed.Scleral bulking was performed if necessary.RESULTS:Sucessful retina re-attachment was accomplishied in all eyes.No visually significant intraoperative complication occurred.All eyes expericend quick recoveray of visual acuity and mild postoperative irritation.One eye developed a recurrent inferior retinal detchment in 20d after the surgery using non-remove technique, and recovered after conventional silicone oil removal and retinal reattachment surgery.CONCLUSION:Two-port 27-gauge pars plana vitrectomy is an efficacious (and potentially cost-efficient) method to treat early stage recurrent retinal detachment in silicone oil dwelling eyes.