Objective:To investigate effects of the autophagy inducer rapamycin and autophagy inhibitor 3-methyladenine on viral structures and biosynthesis of functional proteins in dorsal root ganglia in a guinea pig model of varicella-zoster virus (VZV) infection, and to explore their possible mechanisms.Methods:VZV was cultured and proliferated in human embryonic lung fibroblasts (HELFs) , and peripheral blood mononuclear cells (PBMCs) were isolated from guinea pigs. VZV-HELFs and PBMCs were co-cultured for 18-20 hours, and VZV-PBMCs were collected by centrifugation. Thirty-two guinea pigs were randomly and equally divided into 4 groups (8 mice in each group) : blank control group was injected with autologous PBMCs via the medial canthal venous plexus; autophagy inhibition group, autophagy induction group, and VZV infection group were intraperitoneally injected with 3 mg/kg 3-methyladenine solution, 0.5 mg/kg rapamycin solution, and the same volume of 0.9% NaCl solution respectively, followed 2 hours later by injections with 50 μl of VZV-PBMCs via the medial canthal venous plexus. Fourteen days later, the guinea pigs in each group were sacrificed, and dorsal root ganglion tissues were collected. The transmission electron microscope was used to observe the morphology of virus particles, as well as the morphology and number of autophagic vesicles, Western blot analysis was performed to determine the expression of VZV nucleocapsid protein (NCP) , immediate-early protein 62 (IE62) , and autophagy-related proteins Beclin-1 and p62, and immunohistochemical study to determine the expression of anti-VZV antibodies in VZV-infected dorsal root ganglia. Statistical analysis was carried out by using two-independent-sample t test, one-way analysis of variance, least significant difference- t test or Kruskal-Wallis H test. Results:Nucleocapsid-containing virions and scattered autophagosomes were seen in the dorsal root ganglia in the VZV infection group under the transmission electron microscope. The number of autophagic vesicles significantly differed among the blank control group, VZV infection group, autophagy induction group and autophagy inhibition group ( M[ Q1, Q3]: 0, 5[4, 6], 7[5, 9], 0, respectively; H = 135.60, P < 0.01) , and was significantly higher in the VZV infection group than in the blank control group and autophagy inhibition group (both P < 0.05) , as well as in the autophagy induction group than in the autophagy inhibition group ( P<0.05) , but there was no significant difference between the VZV infection group and autophagy induction group ( P>0.05) . Western blot analysis showed that the expression level of IE62 protein was significantly higher in the VZV infection group (1.49 ± 0.06) than in the blank control group (0.50 ± 0.09, t = 9.17, P < 0.05) ; the expression of anti-VZV antibodies was significantly lower in the autophagy inhibition group than in the autophagy induction group and VZV infection group ( t = 9.24, 7.78, respectively, both P < 0.01) , while there was no significant difference between the autophagy induction group and VZV infection group ( P > 0.05) . Conclusion:Autophagy occurred in the dorsal root ganglia of guinea pigs after VZV infection; the inhibition of autophagy could affect the structure of VZV and decrease the expression of VZV functional proteins in the dorsal root ganglia of guinea pigs.

Objective:To explore the clinical characteristics, diagnosis and treatment of acute leukemia patients during pregnancy.Methods:The clinical data of 16 cases with acute leukemia during pregnancy from January 2009 to December 2018 in the First Affiliated Hospital of USTC were retrospectively analyzed. The diagnosis and treatment regimens, pregnancy outcome, the early fetus and survival status of patients were also analyzed.Results:All 16 leukemia cases were confirmedly diagnosed and classified by bone marrow puncture, including 13 cases of acute myeloid leukemia (5 cases of non-acute promyelocytic leukemia and 8 cases of acute promyelocytic leukemia) and 3 cases of acute lymphoblastic leukemia. At the time of confirmed diagnosis, 6 patients were in first trimester, 6 cases in second trimester and 4 cases in late trimester. As for pregnancy outcome, 1 patient had natural birthing, 5 patients underwent cesarean operation, 9 patients underwent artificial abortion and 1 patient had spontaneous abortion. Chemotherapy was performed in 15 patients during pregnancy, 11 patients received chemotherapy for treatment of primary disease after pregnancy, 3 patients died during the treatment. During the follow-up of 13 cases, 8 patients survived and 5 patients lost follow-up.Conclusions:Early diagnosis of acute leukemia during pregnancy is very important. Bone marrow puncture should be performed timely to make clear diagnosis when blood routine result is abnormal during antenatal care. Multidisciplinary consultation should be initiated in time, and the best treatment plan should be worked out to guard against serious complications during pregnancy.

Objective:This study aimed to examine the safety and efficacy of CD19 chimeric antigen receptor T cell (CD19 CAR-T) therapy in relapsed/refractory Philadelphia chromosome-positive acute B-precursor lymphoblastic leukemia (R/R Ph + B-ALL) . Methods:The clinical data of 14 patients with R/R Ph + B-ALL treated with CD19 CAR-T cell therapy from November 2016 to April 2019 were retrospectively analyzed. Results:Among the 14 patients in this study, 7 were male and 7 were female, with a median age of 33 (7-66) years old. The efficacy was evaluated on the 28th day following CAR-T cells infusion; the overall response rate was 100.0% (14/14) , the complete response (CR) rate was 92.9% (13/14) , and the partial response (PR) rate was 7.1% (1/14) . After CAR-T cells infusion,12 cases (85.7%) developed cytokine release syndrome (CRS) : 1 case of grade 1 CRS, 4 cases of grade 2 CRS, 6 cases of grade 3 CRS, and 1 case of grade 4 CRS. Moreover, one case developed CAR T-cell-related encephalopathy syndrome (CRES) ; 14 cases had Ⅲ-Ⅳ hematological toxicity; and 13 CR cases had B cell dysplasia. These adverse reactions were all controllable. The median follow-up time was 441 (182-923) d. The median overall survival (OS) and progression-free survival (PFS) were 515 [95% confidence interval ( CI) 287-743] days and 207 (95% CI 123-301) days, respectively. Conclusion:CD19 CAR-T cell therapy is safe and effective for R/R Ph + B-ALL treatment. However, the long-term efficacy needs to be further improved.

Background:In patients with diffuse large B?cell lymphoma (DLBCL), central nervous system (CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the effcacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction. Methods:A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis (methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Differences were evaluated using a two?tailed test, andP<0.05 was considered signiifcant. Results:At a median follow?up of 46months, 25 (4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group (P=0.045). Intrathecal chemotherapy prophylaxis did not confer much beneift in terms of preventing CNS relapse. Bone involvement [hazard ratio (HR)=4.21, 95% conifdence interval (CI) 1.38–12.77], renal involvement (HR=3.85, 95% CI 1.05–14.19), alkaline phosphatase (ALP) >110U/L (HR=3.59, 95% CI 1.25–10.34), serum albumin (ALB) <35g/L (HR=3.63, 95% CI 1.25–10.51), treatment with rituxi?mab (HR=0.34, 95% CI 0.12–0.96), and a time to complete remission≤ 108days (HR=0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement (HR=4.44, 95% CI 1.08–18.35), bone marrow involvement (HR=11.70, 95% CI 2.24–60.99), and renal involvement (HR=10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set. Conclusions:In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suffcient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

OBJECTIVEThis study is conducted to explore new methods to perform surface biomodification of titanium implants and improve osteogenic efficiency.

METHODSAn RGD peptide and chitosan (CS) were combined by acylation reaction, forming RGD-CS. An RGD-CS/pDNA complex was subsequently prepared using a complex coacervation method and grafted on a pure titanium surface after physical and biochemical treatments were performed. The chemical structural characteristics of RGD-CS were evaluated using an infrared spectrometer and an elemental analyzer. The shape of this complex was then assessed by gel electrophoresis combined with atomic force microscopy. The grafting effect of this complex on the titanium surface was detected by EB staining.

RESULTSCS and RGD peptides were coupled by an amide bond. The RGD-CS/pDNA complex was completely composited at N/P > or = 2. Atomic force microscopy results showed that the morphology of this complex was mainly spherical. EB staining experiments showed that this complex was successfully grafted on the titanium plate.

CONCLUSIONRGD peptide-modified CS can be used as a titanium implant surface plasmid package carrier of pDNA.

Chitosan ; Dental Implants ; Microscopy, Atomic Force ; Oligopeptides ; Plasmids ; Titanium

OBJECTIVETo investigate the frequency of different types of mature T- and NK-cell lymphomas diagnosed in a 4-year period at Sun Yat-sen University Cancer Center, and to study baseline CD30 for potential anti-CD30 targeted therapy in mature T- and NK-cell lymphoma.

METHODSAll cases of mature T- and NK-cell lymphoma diagnosed at Sun Yat-sen University Cancer Center from September 1, 2009 to August 31, 2013, were reviewed. Paraffin-blocks of available 164 consecutive cases were stained for CD30 immunohistochemistry using EnVision protocol.

RESULTSA total of 625 cases of mature T- and NK-cell lymphomas were diagnosed and the most common type was extranodal NK/T cell lymphoma (ENKTL), nasal type 319 (51.0%) cases, followed by angioimmunoblastic T-cell lymphoma (AITL) (119 cases, 19.0%), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) (81 cases, 13.0%), and anaplastic large-cell lymphoma (ALCL), including 48 cases (7.7%) of systematic ALCL and 11 cases (1.8%) of primary cutaneous ALCL. Besides ALCL, ENKTL had the highest expression rate of CD30 among the 164 cases, with positivity observed in 41 cases (62.1%, 41/66). Only 1 case of PTCL-NOS was CD30 positive. CD30 was not expressed in all 28 cases of AITL and other rare types of mature T- and NK-cell lymphoma.

CONCLUSIONSThe frequency of different types of mature T- and NK-cell lymphoma encountered at Sun Yat-sen University Cancer Center was similar to that seen in other areas of China and other Asia countries. CD30 expression is different among several types of mature T- and NK-cell lymphoma. In addition to ALCL, ENKTL has the highest expression rate of CD30, which may be a candidate disease for anti-CD30 targeted therapy.

China ; epidemiology ; Humans ; Immunohistochemistry ; Killer Cells, Natural ; Lymphoma, Extranodal NK-T-Cell ; epidemiology ; pathology ; Lymphoma, Large-Cell, Anaplastic ; epidemiology ; pathology ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; epidemiology ; pathology ; Lymphoma, T-Cell, Peripheral ; epidemiology ; pathology ; T-Lymphocytes

OBJECTIVETo investigate the effect of cetylpyridinium chloride buccal tablets on halitosis induced by oral conditions.

METHODSWith Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum as the testing bacteria, the minimal inhibitory concentration (MIC) of cetylpyridinium chloride buccal tablets was determined using minute amount serial dilution test. The production of volatile sulfur compounds (VSCs) was measured using sulfide detector halimeter in the anaerobic bacteria culture at 4 and 8 h after addition of the tablets. The effect of the tablets in suppressing odor production by mouth-borne halitosis bacteria was assessed using cysteine challenge test in healthy volunteers, and the effectiveness was evaluated by measuring the reduction in VSCs production and the duration of the effect.

RESULTSCetylpyridinium chloride buccal tablets inhibited the growth of all the 3 bacteria. The tablets obviously inhibited VSCs production by the 3 bacteria with a effect similar to chlorhexidine. Compared with distilled water gargle, the buccal tablets significantly reduced cysteine-induced VSCs production level in the healthy volunteers (P<0.05), and the effect lasted for 230 min.

CONCLUSIONCetylpyridinium chloride tablets can obviously suppress bacteria responsible for oral halitosis and produce good effects in the treatment of halitosis induced by oral conditions.

Cetylpyridinium ; therapeutic use ; Fusobacterium nucleatum ; drug effects ; Halitosis ; drug therapy ; Humans ; Microbial Sensitivity Tests ; Porphyromonas gingivalis ; drug effects ; Prevotella intermedia ; drug effects ; Sulfur Compounds ; analysis ; Tablets ; Volatile Organic Compounds ; analysis

Objective This study is conducted to explore new methods to perform surface biomodification of titanium implants and improve osteogenic efficiency. Methods An RGD peptide and chitosan (CS) were combined by acylation reaction, forming RGD-CS. An RGD-CS/pDNA complex was subsequently prepared using a complex coacervation method and grafted on a pure titanium surface after physical and biochemical treatments were performed. The chemical structural characteristics of RGD-CS were evaluated using an infrared spectrometer and an elemental analyzer. The shape of this complex was then assessed by gel electrophoresis combined with atomic force microscopy. The grafting effect of this complex on the titanium surface was detected by EB staining. Results CS and RGD peptides were coupled by an amide bond. The RGD-CS/pDNA complex was completely composited at N/P≥2. Atomic force microscopy results showed that the morphology of this complex was mainly spherical. EB staining experiments showed that this complex was successfully grafted on the titanium plate. Conclusion RGD peptide-modified CS can be used as a titanium implant surface plasmid package carrier of pDNA.

Objective To analyze the treatment efficacy and safety of a modified GMALL protocol for adult acute lymphoblastic leukemia (ALL). Methods Data of 37 patients with newly diagnosed adult ALL treated with a modified GMALL protocol from January 2005 to December 2009 were retrospectively analyzed,and compared with that of 44 patients treated with an in-house conventional protocol at the same period.Results The complete remission (CR) rate was 89.2 %(33/37) treated with modified GMALL protocol. The cumulative overall survival (OS) rates at 1 year, 2 years, 3 years and 4 years were 77.5 %, 48.0 %, 40.0 %and 40.0 %, respectively. The main adverse events were grade 3 or grade 4 hematological toxicities and infections which were easily managed, and the treatment-related mortality rate was low. The OS of modified GMALL protocol was superior to that of the conventional protocol. Conclusion The modified GMALL protocol has a satisfying effect and the adverse events can be tolerated for adult ALL, so its clinical application can be encouraged.

Objective To discuss the effect of different methods of dropping the high temperature of the tubercular meningitis patients. Methods 35 cases with tubercular meningitis with high fever were divided into research group(11 cases) and control group(24 cases) ,24 patients in control group were treated by traditional cooling method, 11 patients in research group were rteated by mild hypothermia therapy, The self signs, the intracranial pressure,Glasgow scores, complications and the death rates of patients were assessed and compared. Results The effective rates of the research and control cooling method were 81.8% and 41.7% respectively. The difference between the two groups was significant;After the intervention,compared with the control group, the self scale is superior in research group,and the intracranial pressure and the death rates of patients were lower,and patients'Glasgow scores were higher,but the complications between the two groups had no significant differences. Conclusion Mild hypothermia can effectively control patients'temperature,at the same time, which can improve the patients conscious state and reduce the mortality.