Objective To observe the dynamic changes of TNF-α,IL-1β,IL-6,IL-10,and expressions of Notch-1,NF-κB mRNA and their protein levels in the brain tissue of septic mice and intervention effects of intrathecal injection of lentiviral vector of miR-34a gene for regulating Notch-1/NF-κB signaling pathway.Methods A total of 54 mice of clean grade were divided randomly (random number) into four groups,namely sham group (n =9),in which sham-operated laparotomy was performed;CLP group (n=15),in which the cecum ligation operation (CLP) was performed;NC group (n =15),in which intrathecal injection of lentivirus 5 μL (concentration 5 × 108 TU/mL),one time per day,for 3 days,then CLP was performed on the seventh day;intervention group (n =15),in wihch intrathecal injection of miR-34a lentivirus 5 μL (concentration 5 × 108 TU/mL),one time per day,for 3 days,then CLP was performed on the seventh day.The mice of four groups were sacrificed 24 h after modeling or operation.The changes of behavior of mice was observed and the neurological scores were assessed 24 h after CLP.The levels of TNF-α,IL-1β,IL-6 and IL-10 in the brain were measured by ELISA method.The mRNA expression and protein levels of Notch-1 and NF-κB in the brain tissue were measured by real-time PCR and Western blot method,respectively.Pathological changes of brain tissue were observed under light microscope.Results The neurological scores,the cerebral TNF-α,IL-6 levels,the mRNA expression and protein level of NF-κB (P＜0.01),and IL-1β levels (P ＜0.05) in CLP group 24 h after modeling were higher than those in sham group.The cerebral IL-10 level and the mRNA expression and protein level of Notch-1 (P ＜ 0.01) in CLP group 24 h after modeling were lower than those in sham group.The neurological scores,the cerebral TNF-α and IL-1β levels,and the protein level of NF-κB (P ＜0.01),and IL-6 (P ＜ 0.05) in NC group 24 h after modeling were higher than those in sham group.The cerebral IL-10 level,the mRNA expression and protein level of Notch1 in NC group 24 h after modeling were lower than those in sham group.There were no significant difference in neurological socres,IL-1β and IL-6 levels between intervention group and CLP group (P ＞ 0.05).The IL-10 level (P ＜ 0.05) and the mRNA expression (P ＜ 0.05) and protein level (P ＜ 0.01) of Notch-1 in intervention group 24 h after modeling were lower than those in CLP group.There were no significant difference in biomarkers between NC group and CLP group (P ＞ 0.05).The degree of cerebral damage found under light microscope was also ameliorated in intervention group compared with CLP group 24 h after modeling.Conclusions The effects of miR-34a via regulating Notch-1/NF-κB signaling pathway on brain function exerts cerebral protective effects in septic mice.

OBJECTIVETo study glycyrrhizin's anticancer effect and its mechanism.

METHODS3-methylcholanthrene were injected into mice's submandibular glands to induce tumor, then transplanted the tumor pieces (1 mm3) to mice. The transplanted tumors were measured, and flow cytometry analysis and cytomorphology observation were conducted.

RESULTSGlycyrrhizin (GL) inhibited the transplanted mandibular gland fibro-sarcoma of mice and the suitable GL dose for inhibiting fibrosarcoma of mice was 1.61 mg per 20 g weight. The GL dose below 3.22 mg per 20 g weight didn't produce remarkable toxicity and side effects. GL induced cytomorphological changes of tumor cells and enhanced immunosuppression of macrophage on fibrosarcoma. The result of flow cytometry showed that tumor cell counts of GL1 and GL2 groups increased remarkably in DNA synthetic prophase, and decreased in DNA synthetic phase.

CONCLUSIONGL can inhibit transplanted mandibular gland fibro-sarcoma of mice. The anticancer mechanism of GL may be acting on related enzymes with phagocytosis. The result of flow cytometry showed that the shift of fibrosarcoma cells from G1 phase to S phase was blocked. This suggests that the anticancer action of GL is related to its inhibition of ribonucleotide reductase, a rate-limiting enzyme in DNA synthesis.

Animals ; Antineoplastic Agents ; pharmacology ; DNA, Neoplasm ; biosynthesis ; Fibrosarcoma ; chemically induced ; pathology ; Glycyrrhizic Acid ; pharmacology ; Macrophages ; physiology ; Male ; Methylcholanthrene ; Neoplasm Transplantation ; Phagocytosis

Objective To investigate the distribution and resistance profile of bacterial isolates in Shanghai Children's Hospital. Methods Antimicrobial susceptibility of all isolates was determined by Kirby-Bauer disk diffusion method according to 2016 CLSI standard. The data were analyzed by WHONET 5.6 software. Results A total of 23 259 non-duplicate strains were isolated from 2011 to 2016, including 10 885(46.8％)gram-postive cocci and 12 374(53.2％)gram-negative bacilli. The average prevalence of methicillin-resistant S. aureus(MRSA)and coagulase-negative Staphylococcus(MRCNS)was 35.8％ and 82.2％, respectively. The prevalence of MRSA rose from 27.4％ in 2011 to 42.9％ in 2016. The resistance rate of MRSA and MRCNS strains were significantly higher than methicillin sensitive strains. The resistance rate of Enterococcus faecium strains was significant higher than Enterococcus faecalis. The prevalence of non-susceptible Streptococcus pneumoniae was 31.2％(908). No gram-positive strain was resistant to vancomycin or linezolid. The prevalence of carbapenem resistance increased in gram-negative strains. The resistance rate of Klebsiella pneumoniae to imipenem and meropenem rose from 3.1％ and 4.8 ％ in 2011 to 28.7％ and 37.4％ in 2016, respectively.The rate of Pseudomonas aeruginosa resistance to imipenem and meropenem rose from 13.8％ and 16.5％ in 2011 to 18.8％ and 19.4％ in 2016, respectively, while Acinetobacter baumannii showed resistance rate of 38.3％ and 39.9 ％ in 2011 to 68.4％ and 69.7％ in 2016. Conclusions Increasing prevalence of MRSA, carbapenem-resistant K. pneumoniae, extensively drug-resistant A.baumannii has become a concern in clinical practice. Therefore, antimicrobial resistance surveillance should be highly strengthened in children's hospital.

Objective:To investigate the clinical features of elderly rheumatoid arthritis(RA)patients with lung cancer, and to improve clinicians' understanding of this condition.Methods:Retrospective analysis was conducted over general information, clinical manifestations, laboratory results, pathological types, clinical stages, treatment and prognosis in elderly inpatients(≥60 years old)diagnosed with RA and lung cancer admitted to the Second Xiangya Hospital, Central South University from January 2012 to December 2019.Differences between male and female patients were compared.Results:There were 12 elderly patients with RA combined with lung cancer, including 7 males and 5 females, with an average age of(65.8±5.7)years(60-78). The median years from the diagnosis of RA to lung cancer was 11(7.5, 17.3). Eleven patients had clinical symptoms before the diagnosis of lung cancer, with cough and sputum as the most common initial manifestations(9/11). The proportion of smokers in male patients was 71.4%(5/6). Most patients(11/12)had elevated erythrocyte sedimentation rates(ESR)and C-reactive protein(CRP). Eight patients underwent rheumatoid factor(RF-IgM, IgA, IgG)and anti-cyclic citrullinated peptide(ACPA)examinations, and the positive rate was 100% for RF and 87.5% for ACPA.Among 10 patients undergone tumor marker examination, 6 had elevated CEA, 4 had elevated CYFRA21-1, 2 had SCC, 2 had NSE, and 2 had elevated CA125.Among the 12 patients, 7 had adenocarcinoma, 2 had squamous cell carcinoma, 2 had small cell lung cancer, and 1 had carcinoma in situ.Except for 1 case of carcinoma in situ, the remaining 11 patients were all at stage Ⅲ or Ⅳ at the time of diagnosis.Three patients gave up anti-cancer treatment, while the remaining 9 patients received different therapies.In the end, 10 patients died and 2 patients survived so far.The average follow-up time was 17.5(5, 25)months.Further analysis showed that there was no significant difference in clinical manifestations, laboratory test results, pathological types, treatment and prognosis between male and female patients, except that the ESR level was higher in the female group than in the male group(Z=-2.589, P=0.010). However, the average age of male patients was older than that of female patients(68±6.2, 62.6±3.1), and the age of male patients at the diagnosis of RA was also older (56.4±3.8, 52.0±9.5). The proportion of smokers in male patients was significantly higher than in female patients(71.4%, 20.0%), while women had higher proportions than men with elevated CEA(75%, 50%)and NSE(50%, 0.0%). The proportion of women with adenocarcinoma was slightly higher than that of men(80.0%, 42.9%), while the proportions of men with squamous cell carcinoma(28.6%, 0.0%)and small cell carcinoma(28.6%, 0.0%)were slightly higher than those of women.Male patients had a higher mortality rate(100.0%, 60.0%)and a shorter median follow-up time[16.0(2.0, 18.0), 26.0(11.5, 50.0)monthes]. Conclusions:Elderly RA patients with lung cancer are more common in men, and the average age is older than that of female patients.The occurrence of lung cancer is more likely in RA patients with longer disease duration.Most patients are positive with RF and ACPA.Adenocarcinoma is the most common pathological type of lung cancer, and most patients are at clinical stages Ⅲ and Ⅳ.Mortality is high and prognosis is poor.Thus, for elderly RA patients, it is necessary to receive regular monitoring in changes in pulmonary imaging for early detection of lung cancer and improved prognosis.

Objective: To assess clinical features and treatment outcomes in immunocompetent patients with primary central nervous system lymphoma (PCNSL). Methods: Sixty-two patients with PCNSL who attended Guangdong General Hospital between January 1998 and January 2012 were included. Survival curves were estimated using Kaplan-Meier survival methodology and statistical significance of continuous was assessed via the Cox proportional hazard model. Results: The median age of the patient cohort was 56 years, and the male to female ratio was 1.14∶1.00. The common presentations were increased intracranial pressure symptoms and neuron damage. Performance status of 54 (54/62, 87.1%) patients were the international prognostic index (IPI) 0-2. Diffuse large B-cell lymphoma (57/62, 91.9%) was most common, and the rest were T-cell lymphoma (4/62,6.4%) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (1/62, 1.6%). In the series, 32 patients (32/62, 51.6%) had multiple lesions. Involvement of deep structures was found in 30 (30/62, 48.4%) patients. An elevated serum LDH level was detected in 19 (19/62, 30.6%) patients and the Ki-67 index was ≥90% in 38 (38/62, 61.3%) patients. Univariate analysis showed patients who were female, age<60 years, had WHO Eastern Cooperative Oncology Group performance status grade 0-2, single lesion, absence of deep structures involvement and normal LDH level showed better 2-year survival rate and longer median survival time. Significance was only seen in the normal LDH level group. Multivariate Cox regression analysis revealed that radical surgery only and Rituximab+ high-dose of methotrexate+ whole brain radiation therapy (WBRT) were independent prognostic indicators in PCNSL patients (P<0.05). Conclusions PCNSL is a rare but aggressive tumor with poor prognosis. Patients treated with high-dose of methotrexate combining with rituximab, followed by WBRT have a better prognosis and longer survival time, and thus these could probably be a promising treatment.

Objective To investigate clinically and in laboratory a genealogical tree with hemoglobin H disease Combining Hemoglobin Q-Thailand and Hemoglobin E Disease.Methods Genealogical laboratory studies were carried out with the following methods:hemoglobin electrophoresis, various biochemical determinations,and DNA analysis.Results Father's genotype of ?-THAL:??/?~Q ?~(4.2); genotype of ?-THAL:?E/N;phenotype:minor ?-THAL carrier combining Hb Q and Hb E multiple heterozygote;mother' s genotype of ct-THAL:--~(SEA)/??;genotype of ?-THAL:?n/?n.According to comprehensive analysis,mother's phenotype:minor ?-THAL,complex minor ?-THAL carrier combining Hb F ? Initial sign of ?-THAL genotype:--~(SEA)/?~Q ?~(4.2);phenotype:deletion type Hb H genotype disease;?- THAL genotype:?E/?E;phenotype:? E homozygote.According to comprehensive analysis:deletion type Hb H combining HbE multiple heterozygote.Youger brother's ?-THAL genotype:--~(SEA)/?~Q ?~(4.2);?-THAL genotype:?n/?n;phenotype:deletion type Hb H disease.Both mother and her youngest son have G6PD deficiency.Conclusions Guangdong Province is an area with high morbidity of ?-THAL and ?-THAL,Hb E and Hb Q as well as G6PD deficiency.There may be some correlation between Hb E and Fib Q in term's of the high morbidity of regional Hb,but the two types of Hb combining Hb H disease are rare in China and the world in point of nonhomologous chromosome.Attention should be paid to the problems of double heterozygote of ?-THAL complex ?-THAL,and THAL complex G6PD deficiency.Data from the study have enriched the scientific information of molecular genetics of erythroeyte thalassemia and of molecular pathology with important significance in genetics guidance and clinical treatment for patients.

OBJECTIVETo investigate the clinical feasibility of cell-free fetal DNA (cffDNA)-based noninvasive prenatal diagnosis of β-thalassemia.

METHODSNine samples of amniotic fluid were obtained to detect the 8 common and 9 relatively rare mutation sites of β-thalassaemia in Guangdong Province. The maternal blood samples were also collected for extracting and purification of the cffDNA, and a duplex PCR was performed using 3 pairs of primers and the fetal β-globin genotype was analyzed by reverse dot-blot hybridization.

RESULTSAmong the 9 cases, 5 showed fetal genotypes of β-thalassemia inherited from the father by examination of the amniotic fluid, and 2 fetuses were identified to have β-thalassemia genes inherited from the father determined based on the cffDNA in the maternal blood.

CONCLUSIONSThe cffDNA-based noninvasive prenatal diagnosis is feasible for β-thalassemia, but the contamination of the maternal background DNA results in a low detection rate.

Adult ; Cell-Free System ; DNA ; blood ; Female ; Fetal Diseases ; diagnosis ; genetics ; Fetus ; Genetic Testing ; Humans ; Pregnancy ; blood ; Prenatal Diagnosis ; methods ; Young Adult ; beta-Thalassemia ; diagnosis ; genetics

OBJECTIVETo probe into the mechanism of substance-partitioned moxibustion in treatment of primary dysmenorrhea (PD) of cold-damp stagnation type.

METHODSThe treatment group (105 cases of PD) were treated with substance-partitioned moxibustion and the control group (104 cases) were treated with Chinese drug Yueyue-shu. Their therapeutic effects were observed. Plasma beta-endorphin contents in menstrual period were determined before and after treatment in 40 patients of each group.

RESULTSThe total effective rate of 95.2% in the substance partitioned moxibustion group was better than 85.6% in the control group (P < 0.05); after treatment, plasma beta-endorphin content significantly increased in the substance-partitioned moxibustion group (P < 0.01).

CONCLUSIONSubstance-partitioned moxibustion has obvious therapeutic effect on primary dysmenorrhea of cold-damp stagnation type, which is carried out possibly through regulating the plasma beta-endorphin content as one of the mechanisms.

Adolescent ; Adult ; Cold Temperature ; Dysmenorrhea ; blood ; therapy ; Female ; Humans ; Menstrual Cycle ; Moxibustion ; Premenstrual Syndrome ; complications ; therapy ; Thermosensing ; beta-Endorphin ; blood

OBJECTIVETo investigate the absorption characteristics and transportation mechanism Yangyin Tongnao granules in main effective fractions in Caco-2 cell model.

METHODThe safety concentrations of Yangyin Tongnao granules in main effective fractions in Caco-2 cells. A Caco-2 cell model was established to study the transport situations after the compatibility of Yangyin Tongnao granules in main effective fractions, and the content was determined by high performance liquid chromatography (HPLC).

RESULTP(app) of puerarin, ligustrazine and astragaloside were less than 1.0 x 10(-6) cm x s(-1), and their P(app) were hard to be close to atenolol. The oral absorption in descending order is shown as the following: puerarin, ligustrazine, astragaloside. After the compatibility between saponins and flavonoids, P(app) of astragaloside was improved obviously, which promoted the transport from apical (AP) to basolateral (BL); the compatibility of puerarin, ligustrazine and astragaloside showed a significant effect in the efflux of astragaloside and no change in the absorption transport of ligustrazine and puerarin at the same time. There is a great difference in bidirectional transport of representative component of each effective fraction, and P(app)(B --> A) was significantly greater than Papp(A --> B), which suggested that the efflux transport from BL side to AP side had an advantage in the three representative components of the three effective fractions in Caco-2 cell monolayer model.

CONCLUSIONAstragaloside, ligustrazine and puerarin may be malabsorptive compounds, and the three compounds may be discharged by the transport protein in small intestine membrane.

Biological Transport ; Caco-2 Cells ; Drugs, Chinese Herbal ; metabolism ; pharmacokinetics ; Humans ; Intestinal Absorption ; Intestines ; metabolism ; Tablets ; metabolism ; pharmacokinetics

OBJECTIVETo study the clinical, pathologic, immunophenotype, molecular characteristics and prognosis of HIV-negative plasmablastic lymphoma (PBL).

METHODSTwelve cases of HIV-negative PBLs diagnosed between 2005 and 2014 in Guangdong General Hospital were identified according to WHO classification of tumors of haematopoietic and lymphoid tissues (2008). The clinicopathologic features and outcome were analyzed and the relevant literatures were reviewed.

RESULTSThe patients were predominantly male (11/12) with a median age of 55.5 years. The tumor cells showed the characteristic combination of immunoblastic/plasmablastic morphology, plasma cell phenotype and high proliferation, no expression of mature B cell markers. 7/10 of the cases were EBER positive. Two cases were positive for C-myc translocation. Four of twelve patients were died.

CONCLUSIONSPBL is a rare, aggressive B-cell lymphoma. HIV-negative PBL has lower rate of oral involvement and EBER expression than HIV-positive patients, the differential diagnosis is very challenging, and the prognosis is worse.

Diagnosis, Differential ; Female ; HIV Seronegativity ; Humans ; Immunophenotyping ; Lymphoma, B-Cell ; diagnosis ; Male ; Middle Aged ; Plasma Cells ; classification ; Plasmablastic Lymphoma ; diagnosis ; pathology ; Prognosis ; Translocation, Genetic