Efficacy and safety of fourth-generation CD19 CAR-T expressing IL7 and CCL19 along with PD-1 monoclonal antibody for relapsed or refractory large B-cell lymphoma / 中华血液学杂志

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.

A prospective observation for the patients with type 2 diabetes mellitus complicated with stroke / 预防医学

Objective To learn the stroke occurrence status and the influencing factors of the patients with type 2 diabetes,and to provide the basis for the prevention of stroke.Methods Patients with type 2 diabetes which were reported in 2011 year from the system of chronic disease monitoring information management of Zhejiang Province were selected and followed -up until October in 2014.Stroke occurrence were recorded and the influencing factors were analyzed.Results The incidence rate was 5.22％ (59/1 129),and the annual incidence was 1.56％.Fifty six cases (94.92％) were ischemic stroke.Logistic regression analysis showed that older than 65 and hypertension were risk factors for type 2 diabetes complicated with stroke.The group of 65-and 75-were associated with higher risk of stroke than 45-(OR =3.38,95％ CI:1.39-8.24;OR =7.77,2.14-28.24).Hypertensionin were the influencing factors of stroke among patients with type 2 diabetes (OR =10.92,95％ CI:5.94-20.09).Conclusion Older age and hypertension were risk factors for type 2 diabetes complicated with stroke.Therefore effective control blood pressure among older patients with type 2 diabetes should be strengthed to prevent stroke.

Interferon-γ Alters the Immune-related miRNA Expression of Microvesicles Derived from Mesenchymal Stem Cells / 华中科技大学学报（医学）（英德文版）

Increasing studies have demonstrated that interferon gamma (IFN-γ),which serves as a critical inflammatory cytokine,is essential to induce the immunosuppressive effects of mesenchymal stem cells (MSCs).However,the mechanisms underlying the enhanced immunosuppressive effects of IFN-γ-stimulated MSCs (γMSCs) are not fully understood.MSC-derived rnicrovesicles (MSC-MVs) have been viewed as potential pivotal mediators of the immunosuppressive effects of MSCs.Moreover,microRNAs (miRNAs) are important regulators of immunological processes and can be shuttled from cell to cell by MVs.The aim of our study was to analyze the the miRNA expression signature of MVs derived from γMSCs (γMSC-MVs),which may provide better understanding of the immunosuppressive property of their parent cells.Through miRNA microarray and bioinformatics analysis,we found 62 significantly differentially expressed miRNAs (DEMs) in γMSC-MVs compared with MSC-MVs.And the potential target genes and signaling pathways regulated by DEMs were predicted and analyzed.Interestingly,many DEMs and predicted signaling pathways had been.demonstrated to be involved in immunoregulation.Furthermore,the network between immunoregulation-related pathways and relevant DEMs was constructed.Collectively,our research on the miRNA repertoires of γMSC-MVs not only provides new perspectives into the mechanisms underlying the enhanced immunosuppressive property of γMSCs,but also paves the way to clinical application of these potent organelles in the future.

Health hazards of hexavalent chromium in drinking water / 中华地方病学杂志

Objective To learn the exposure levels and health hazards of long-term exposure to hexavalent chromium (Cr6+) through drinking water in a west county,and to provide a scientific basis for making preventive measures.Methods Five water points were selected to test the Cr6+ concentration of drinking water in the county in 2015,data of 3 water points with water Cr6+ concentrations exceeded the standard (Cr6+ ＞ 0.05 mg/L) were selected from 12 drinking water points in some west counties in the recent six years (2009-2014) as the exposed group,2water points that drinking water Cr6+ concentrations not exceeded the standard (Cr6+ ≤0.05 mg/L) in the county and adjacent to the exposed group were selected as the control group.Sixty villagers were selected as the investigation objects in each water point to conduct internal medicine,ears,nose,throat (ENT),dermatology and health examination,urinary chromium content,routine blood and urine test were done.Determination of hexavalent chromium concentration in drinking water was done according to The Drinking Water Standard Examination Method 1,5-diphenylcarbazide Spectrophotometry (GB/T 5750-2006);routine urine was tested using the 10 urine analyzer test;urinary chromium was tested using graphite furnace atomic absorption spectrometer;routine blood five classification was tested using automatic blood analyzer;determination of drinking water hexavalent chromium concentration was done according to The Hygienic Standard for Drinking Water (GB 5749-2006).Higher than 0.05 mg/L was judged as exceeded the standard;physical examination was done according to The Diagnostic Criteria of Occupational Chromium Nasal Disease (GB Z12-2002) and The Diagnostic Standard of Occupational Contact Dermatitis (GB Z20-2002).Results There were 184 and 109 people in the exposed group and the control group,respectively.The average concentration of Cr6+ exceeding the standard ratio was 2.82-3.22 in drinking water,the nasal septum nucosa perforation,skin erythema edema,skin ulcers were 4.9％ (9/184),4.3％ (8/184) and 4.3％ (8/184) in the exposed group,and the urinary chromium level (0.31 μg/L) in the exposed group was significantly higher than that of the control group (0.27 μg/L,Z =-4.078,P ＜ 0.05).Routine blood test result of mean corpuscular haemaglobin (MCH) was (29.56 ± 2.07) pg,platelet counts (PLT) was (222.38 ± 47.53) × 109/L and plateletcrit (PCT) was (0.25 ± 0.05)％ in the exposed group,it was all higher than those of the control group [(29.03 ±2.95) pg,(211.74 ±75.27)× 109/L,(0.24 ± 0.08)％,t =1,940,2.318,2.079,all P ＜ 0.05];standard difference coefficient of variation of red blood cell distribution width (RDW-CV) was (13.14 ± 1.05)％,lymphocyte number (LYMPH) was (2.01 ± 0.64) × 109/L in the exposed group,it was all lower than those of the control group [(13.38 ±1.54)％,(2.21 ± 1.02) × 109/L,t =-1.989,-1.956,all P ＜ 0.05].The positive rate of glycosuria,uric bravery red,and urine nitrite in routine urine test of exposed group was 17.39％ (32/184),23.36％ (43/184),7.61％ (14/184);it was all higher than those of the control group [(8.25％ (9/109),11.93％ (13/109),0.91％ (1/109),x2 =4.746,5.798,6.309,all P ＜ 0.05].Conclusions Urine chromium accumulation has been found in populations long-term exposed to 2.82-3.22 times excessive Cr6+ through drinking water,which has affected the population's health to some extent.Therefore,it is necessary to speed up the local drinking water improvement project.

The efficacy and complication analysis of interspinous dynamic device (Wallis) in patients of degenerative lumbar disease / 中华外科杂志

<p><b>OBJECTIVES</b>To review degenerative lumbar disease treated with Wallis and the re-herniation cases after the implantation of Wallis, so as to evaluate the effect of the device.</p><p><b>METHODS</b>From January 2009 to June 2010, a retrospective analysis was done and 48 patients (30 males and 18 females) with an average age of 43 years (ranging from 17 to 69 years), who received stabilization of the segment using the Wallis device, were reviewed. The involved segments included: 4 cases at L(3-4), 38 cases at L(4-5), 6 cases at L(5)-S(1). Preoperative and postoperative visual analogue scales (VAS) and Oswestry disability index (ODI) were recorded to evaluate the clinical efficiency, imageology diversity was assessed by X-rays and MRI.</p><p><b>RESULTS</b>All cases received fenestration and the implantation of Wallis. No surgery related complications were recorded. There were 48 cases were followed up. The average follow-up period was (20 ± 4) months (12 - 30 months). The average ODI score dropped from 46 ± 10 to 24 ± 7 (t = 12.765, P < 0.05). The average VAS for back and leg pain dropped from 8.1 ± 1.6 to 2.1 ± 1.1(t = 21.881, P < 0.05). Six patients with recurrent lower back and leg pain were diagnosed by MRI, as recurrent herniation (6/48, 12.5%). All re-herniation occurred at L(4-5) level, between 2 and 13 months after the surgery. Three of the 6 patients underwent additional discectomy and fusion, others received conservative treatment.</p><p><b>CONCLUSIONS</b>Although existing problems such as recurrence after surgery, the clinical outcome of Wallis in treating protrusion of lumbar intervertebral disc and lumbar stenosis is satisfied in middle-early stage.</p>

Genetic diversity of Eucommia ulmoides by RAPD analysis / 中国中药杂志

<p><b>OBJECTIVE</b>To determine the genetic diversity of Eucommia ulmoides.</p><p><b>METHOD</b>260 samples of 20 populations were analyzed through radom amplified polymorphic DHA (RAPD).</p><p><b>RESULT</b>Total polymorphic loci percentage was 96.36 and the average was 38.92. 110 bands were produced with 10 random primers and 106 were polymorphic. Nei's gene diversity (H) was 0.246 1, Shannon's Information index(I) was 0.386 8, Gst was 0.424 4, indicating that 42.44% of the genetic variation was distributed among populations and 57.65% within populations.</p><p><b>CONCLUSION</b>The genetic variation was relatively high in E. ulmoides, so the genetic diversity conservation principle should mainly focus on protection of the populations.</p>