Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

Background:The increasing prevalence of colorectal cancer (CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment.We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods:We conducted a multicenter,cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014.Each enrolled patient was interviewed using a structured questionnaire.All expenditure data were inflated to the 2014 Chinese Yuan (CNY;1 CNY =0.163 USD).We quantified the overall expenditure and financial burden and by subgroup (hospital type,age at diagnosis,sex,education,occupation,insurance type,household income,clinical stage,pathologic type,and therapeutic regimen).We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results:A total of 2356 patients with a mean age of 57.4 years were included,57.1％ of whom were men;13.9％ of patients had stage Ⅰ cancer;and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY,and the expenditures for stage Ⅰ,Ⅱ,Ⅲll,and Ⅳ disease were 56,099 CNY,59,952 CNY,67,292 CNY,and 82,729 CNY,respectively.Non-medical expenditure accounted for 8.3％ of the overall expenditure.The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY,which accounted for 59.9％ of their previous-year household income and caused 75.0％ of families to suffer an unmanageable financial burden.Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups (P ＜ 0.05),except for sex.Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less (all P ＜ 0.05).Conclusions:For patients in China,direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable.The financial burden varied among subgroups,especially among patients with different clinical stages of disease,which suggests that,in China,CRC screening might be cost-effective.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

AIM:To investigate whether Notch1 changes stemness and chemotherapeutic sensitivity in human glioma U251 cells.METHODS: The lentiviral vectors, which expressed Notch1-shRNA or Notch1 intracellular domain ( NICD) , were transfected into U251 cells .Western blot and immunofluorescence staining were applied to monitor the va-lidity of the cells, down-regulation of Notch1 expression or over-expression of NICD.The proportion of CD133 +cells was analyzed by flow cytometry.The expression of nestin and GFAP was identified by immunofluorescence staining.The forma-tion rate of tumor cell spheres and the implanted tumor growth in SCID mice were observed.MTT assay was performed to e-valuate the chemotherapeutic sensitivity to VM-26 and BCNU of the cells with different treatments.RESULTS:Stemness was significantly enhanced in the cells over-expressing NICD.For example, the proportion of CD133 +cells was increased, the expression of nestin was up-regulated, the expression of GFAP was down-regulated, and the formation rate of tumor cell spheres and implanted tumor growth were increased.The chemotherapeutic sensitivity to VM-26 and BCNU of the cells was decreased.In the cells with Notch1 gene down-regulation by RNAi, the stemness was inhibited and chemotherapeutic sensi-tivity was increased.CONCLUSION:Notch1, which leads to the change of stemness and chemotherapeutic sensitivity in human glioma U251 cells, is likely to be a potential molecular target for treatment of glioma.

Brain Neoplasms ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Neoplasm Recurrence, Local ; Nestin ; metabolism ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; surgery ; Temporal Lobe ; Vimentin ; metabolism

The effects of cephradinum and ceftazidime on the metabolism of Escherichia coli (E. coli) DH5alpha was determined by microcalorimetry. The microbial activity was recorded as power-time curves through an ampoule method with a TAM Air Isothermal Microcalorimeter at 37 degrees C. The parameters such as the growth rate constant (k), inhibitory ratio (I), the maximum power output (Pm) and the time (tm) corresponding to the maximum power output were calculated. The results show that the ceftazidime has a better inhibitory effect on E. coli DH5alpha than cephradinum.
Anti-Bacterial Agents ; administration & dosage ; pharmacology ; Calorimetry ; methods ; Ceftazidime ; administration & dosage ; pharmacology ; Cephradine ; administration & dosage ; pharmacology ; Escherichia coli ; drug effects ; growth & development ; metabolism ; Microbial Sensitivity Tests

OBJECTIVEHuman growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency.

METHODSA 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed.

RESULTSAfter 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism.

CONCLUSIONSrhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.

Child ; China ; Dwarfism, Pituitary ; blood ; drug therapy ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; deficiency ; therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Male ; Prospective Studies ; Recombinant Proteins ; therapeutic use

OBJECTIVETo investigate the mRNA and protein expression of nucleostemin (NS) in human esophageal squamous cell carcinoma.

METHODSThe mRNA and protein expression of NS were detected in 31 mucosal atypical hyperplasia specimens, 62 esophageal squamous cell carcinoma specimens and the matched normal esophageal mucosa samples by RT-PCR and immunohistochemistry method, respectively.

RESULTSThe positive expression rate of NS protein in normal esophageal mucosa, atypical hyperplasia and esophageal squamous cell carcinoma was 17.7% (11/62), 41.9% (13/31) and 69.4% (43/62), respectively. There was a significant difference among the above three groups (chi2 = 33.676, P < 0.01). The expression levels of NS mRNA in esophageal squamous cell carcinoma (0.971 +/- 0.121) was significantly higher than that in the atypical hyperplasia (0.913 +/- 0.085) and also in the normal esophageal mucosa (0.866 +/- 0.103; F = 14.829, P < 0.01). The expression level of both NS protein and mRNA was positively correlated with histological grade, infiltration depth, and lymph node metastasis (P < 0.05), but not with age, gender or pathological type (P > 0.05).

CONCLUSIONOur results indicate that nucleostemin mRNA and protein are over-expressed in human esophageal squamous cell carcinoma, and it may be related with its oncogenesis.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Carrier Proteins ; biosynthesis ; genetics ; Esophageal Neoplasms ; metabolism ; pathology ; Esophagus ; pathology ; Female ; GTP-Binding Proteins ; Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucous Membrane ; metabolism ; Neoplasm Invasiveness ; Neoplasm Staging ; Nuclear Proteins ; biosynthesis ; genetics ; Precancerous Conditions ; metabolism ; pathology ; RNA, Messenger ; metabolism

OBJECTIVETo establish the quality standard of PsL injections containing mainly 5F (ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid).

METHODThe identification of PsL was performed by thin-layer chromatography, and the content was determined by HPLC. The column was Hypersil C18 (4.6 mm x 250 mm, 5 microm), the mobile phase was the mixture of methane-water-acitic acid (55:45: 0.045) with a flow rate of 1.0 mL x min(-1), the detective wavelength was 254 nm, and the column temperature was maintained at 35 degrees C. The pH value and K+ content of the three batchs injection were determined with pH meter and flame photometric meter, and the contents of tannin, protein, oxalic acid salt and heavy metals were detected by deferent methods.

RESULTThe TLC method was suitable for the identification of PsL5F. The linearity for 5F was obtained over the range of 30-240 microg x mL(-1) (r = 0.999 8), the average recovery of 5F was 99.8%. The injections were of pH value range from 7.80 to 8.20, K+ contents less than 10 mmol x L(-1), and the contents of tannin, protein, oxalic acid salt and heavy metals were qualified with the Chinese pharmacopoeia, respectively.

CONCLUSIONIt's sensitive and reliable that can be used as quality control methods of PsL5F injections.

Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ; Diterpenes ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Injections ; Reproducibility of Results