Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis / 中华内科杂志

Objective:To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM.Methods:Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression.Results:A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly ( OR=1.06, P=0.048 ) , hyponatremia( OR=0.81, P=0.020), high protein level in cerebrospinal fluid (CSF) ( OR=3.32, P=0.033), cerebral infarction( OR=10.50, P=0.040) and hydrocephalus( OR=8.51, P=0.049) were associated with poor prognosis in TBM patients. Conclusions:The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

Characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza / 中华内科杂志

Objective:To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza.Methods:This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups.Results:A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4 +T, CD8 +T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/μl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/μl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/μl respectively]. Meanwhile, the T cells and CD8 +T counts in fatal patients [370 (260,537) cells/μl and 87 (74,105) cells/μl] were significantly lower than those in severe and alive patients [722 (390,990) cells/μl and 222 (154,404) cells/μl]. CD8 +HLA-DR/CD8 +and CD8 +CD38 +/CD8 +T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8 +HLA-DR/CD8 +count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8 +T cell count ( OR=0.952, 95 %CI 0.910-0.997, P=0.035) and CD8 +HLA-DR/CD8 +T ( OR=0.916, 95 %CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later. Conclusions:All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8 +T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

Characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza / 中华内科杂志

Objective@#To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza.@*Methods@#This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups.@*Results@#A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4+T, CD8+T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/μl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/μl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/μl respectively]. Meanwhile, the T cells and CD8+T counts in fatal patients [370 (260,537) cells/μl and 87 (74,105) cells/μl] were significantly lower than those in severe and alive patients [722 (390,990) cells/μl and 222 (154,404) cells/μl]. CD8+HLA-DR/CD8+and CD8+CD38+/CD8+T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8+HLA-DR/CD8+count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8+T cell count (OR=0.952, 95%CI 0.910-0.997, P=0.035) and CD8+HLA-DR/CD8+T (OR=0.916, 95%CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later.@*Conclusions@#All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8+T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

Cardiotoxicity evaluation of three novel proteasome inhibitors in zebrafish / 中国药科大学学报

@#To evaluate the cardiotoxicity of three novel proteasome inhibitors(NNU395, NNU458 and NNU459)in zebrafish, normal developmental zebrafish embryos at 6 hours post fertilization(hpf)were treated with different doses of NNU395 and NNU458 and NNU459 until 72 hpf, the zebrafish mortality was counted. Morphologic changes of the cardiovascular system were observed under a stereomicroscope, and the number of heart beats within 1 min was determined. The expression of cardiac development-related genes in zebrafish was detected by RT-qPCR(Quantitative Real-Time PCR). Results showed that NNU395, NNU458 and NNU459 increased the mortality of zebrafish in a concentration-dependent manner and the values of LC50(50% lethal concentration)were(179. 7±12. 2), (27. 5±1. 3)and(24. 4±2. 6)μmol/L, respectively. Moreover, the toxicity of our three compounds in zebrafish are less when compared with their modified precursors. Upon administration of NNU395 at the concentrations of 120- 200 μmol/L, and NNU458 or NNU459 at the concentration of 30 μmol/L, the zebrafish showed obvious pericardial edema cardiac malformation. 120- 200 μmol/L NNU395 and 0. 1- 30 μmol/L NNU458 or 10- 30 μmol/L NNU459 significantly reduced the heart rate of zebrafish. All of three compounds at the tested concentration had no significant effects on the expression of the heart development-related genes in zebrafish. Our results suggested that low concentrations of NNU395, NNU458 and NNU459 have no obvious toxicity on cardiac development of zebrafish. While, higher concentrations of them showed cardiovascular toxicity on zebrafish.

A randomized controlled study of peramivir, oseltamivir and placebo in patients with mild influenza / 中华内科杂志

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

The evaluation of training program "resident team leader in the Department of General Internal Medicine" at Peking Union Medical College Hospital / 中华内科杂志

Objective To evaluate senior resident training program "resident team leader in the Department of General Internal Medicine" at Peking Union Medical College Hospital.Methods We surveyed the residents or the fellows who had been selected as resident team leaders and received the training from October 2014 to September 2018 on their comments and suggestions.Results Twenty-two rotated senior residents who were selected as team leaders in the Department of General Internal Medicine completed the survey.Almost all(21/22,95.5％) of the respondents reported that they learnt more in general as team leaders by Visual Analog Scale (VAS).The mean VAS scores of clinical skills were 7.23±1.27,7.86± 1.32 in teaching abilities,8.14±0.89 in leadership evaluation.Scales as chief resident assistants were 8.44± 1.26.Sixteen respondents (72.7％)considered that pre-job training by attending doctors was necessary.Another 8 (36.4％)respondents addressed their demands on training of teaching skills.Conclusions The senior resident training program "resident team leader in the Department of General Internal Medicine" improves the competency of rotated senior residents.It is a valuable pilot study on senior resident training and worthy of further application in other departments and hospitals.

Monthly prescription comment on antimicrobial agents at outpatient and emergency department for 5 years: performance of antimicrobial stewardship / 中华医院管理杂志

Objective To retrospectively analyze the implementation of the antimicrobial agents prescription monthly review at the emergency and outpatient departments for the past five years, for evaluation of its action in promoting rational application of antimicrobial drugs. Methods At the baseline investigation stage, 1780 prescriptions on antibiotics in emergency and outpatient department from June 2012 to November 2012 were randomly selected for centralized evaluation. The period of correction and observation falls into two stages. The first stage ranged from December 2012 to February 2015, when the prescription of antibiotics was sampled manually for monthly review. The second stage ranged from March 2015 to June 2017, when a prescription review software for prescription comment was introduced for the sample purpose. The data so acquired were subject to chi-square test and linear regression analysis using Excel 2010 and SPSS 16. 0. Results The rational rate of prescription for antibiotics at the emergency department increased from 80. 56％ of the baseline stage to 99. 47％ of the second stage (166506/167400), scoring a difference of statistical significance (P<0. 001). With intervention of the prescription review software, the percentage of irrational use of antimicrobial agents dropped by 5. 18％ compared to the baseline stage. Conclusions Monthly prescription review on antimicrobial agents at the outpatient and emergency departments could promote the rational use of antimicrobial agents and play an important role in clinical drug safety. Information system and performance assessment contributed to the effect of prescription review.

Clinical features of adult patients with chronic active Epstein-Barr virus infection / 中华内科杂志

Objective To investigate the clinical features of adult-onset chronic active Epstein-Barr virus infection (CAEBV). Methods A total of 21 adult patients with CAEBV who were admitted to the department of General Internal Medicine at Peking Union Medical College Hospital from January 2006 to January 2016 were retrospectively analyzed. Demographic data, disease duration, clinical manifestations, laboratory findings, treatments and prognosis were reviewed. Results Eighteen females and 3 males were enrolled with a mean age of 39 years. The most common clinical manifestations included fever in 20 patients, splenomegaly in 20 patients, lymphadenopathy in 18 patients, and hepatomegaly in 10 patients, followed by laryngopharyngeal disorders in 6 patients, pleural effusion and peritoneal effusion each in 5 patients, rash in 4 patients, interstitial lung disease in 3 patients, gastrointestinal hemorrhage in 2 patients, and peripheral neuropathy and pulmonary hypertension each in 1 patient. Six patients were complicated with hemophagocytic lymphohis-tioncytosis(HLH) that developed 5-17 (mean: 9) months following CAEBV onset, all of whom experienced hyperpyrexia, pancytopenia, lymphadenopathy, splenomegaly, and liver dysfunction, 3 with hepatomegaly. Nineteen of the 21 patients had received steroid therapy including 10 combined with immunosuppressive agents, 11 with antiviral therapy, and 8 with intravenous immunoglobulin. Thirteen patients died, including 10 of multiple organ failure, (including 6 of HLH) 2 of severe pulmonary infection, and 1 of lymphoma. Six patients remained on follow-up, yet 2 were missing. Conclusions CAEBV is expected with severe condition and poor prognosis, which is likely to be complicated with HLH. Clinical physicians should pay attention to adult patients with fever, hepatosplenomegaly and lymphadenopathy, which suggests possible CAEBV.

Effect of FAM83A on stem cell-like traits, chemosensitivity and radiosensitivity of pancreatic cancer cells PANC-1 / 中华放射医学与防护杂志

Objective To investigate the effect of FAM83A on the stem cell-like phenotype, chemosensitivity and radiosensitivity of PANC-1 cells, aiming to provide new ideas for clinical combination therapy of pancreatic cancer. Methods The PANC-1 cells with stable silencing FAM83A were constructed by using lentivirus and validated by qPCR and Western blot. Flow cytometry was used to detect the number of CD133 positive cells and cellular apoptosis; the sphere formation assay was used to test the ability of sphere formation of PANC-1 cells;the effect of gecitabine on the cell viability was detected by MTT assay;the effect of radiation on the proliferation of PANC-1 cells was detected by colony formation assay; the effect of FAM83A on Wnt/β-catenin pathway was examined by Western blot. Results The expressions of FAM83A protein ( 0.83 ± 0.08 ) and mRNA ( 0.29 ± 0.03 ) in PANC-1 cells with stable silencing FAM83A were significantly lower than those in the scrambled control group, respectively (1.95 ± 0.19, 0.98 ± 0.09;t=9.410, 12.600, P<0.05). After silencing FAM83A, the expression of stem cell marker CD133 (8.97 ± 0.62) and the sphere formation ability (8 ± 1) also decreased significantly compared with the scrambled group, respectively (21.60 ± 2.60, 25 ± 3; t=8.184, 9.311, P<0.05), and the stem cell-like phenotype of PANC-1 cells was also significantly inhibited. When PANC-1 cells were silenced by FAM83A and further treated with 50 μmol/L gecitabine at 72 h, the activity of FAM83A-silenced PANC-1 cells (32.33 ± 3.05)％ was significantly lower than that of the gecitabine alone treated group (63.06 ± 5.98)％ (t=6.378, P<0.05), and the apoptosis rate of FAM83A-silenced PANC-1 cells (76.52 ± 8.34) ％ was significantly higher than that of gemcitabine alone group (40.88 ± 4.91)％(t=7.929, P<0.05). After silencing FAM83A combined with IR irradiation, the activity of PANC-1 cells (43.25 ±4.21)％ was significantly lower than that of IR alone (78.13 ± 7.98)％ (t=6.694, P<0.05), and the apoptosis rate (44.56 ± 5.32)％ was significantly increased compared with IR alone (15.15 ±1.95)％ (t = 8.990, P < 0.05). After silencing FAM83A, the expression of Active-β-catenin was significantly decreased while the expression of p-β-catenin was significantly increased, the expression of β-catenin in the nucleus was significantly reduced, although total β-catenin had no significant change, and the activity of Wnt/β-catenin signaling pathway was significantly inhibited. Conclusions Silencing FAM83A could significantly reduce the stem cell-like traits and enhance the chemosensitivity and radiosensitivity of pancreatic cancer cells to gemcitabine and radiation via Wnt/β-catenin signaling pathway, which may provide a new target for targeted and combination therapy of pancreatic cancer.

Inhibition of FOXD1 gene expression increases radiosensitivity of colorectal cancer HCT116 cells / 中华放射医学与防护杂志

Objective To study the effect of inhibiting the expression of FOXD1 gene on the radiosensitivity of colorectal cancer cells. Methods The expressions of FOXD1 mRNA and protein in human colorectal cancer tissues and cells were detected by Real-time PCR ( qRT-PCR) and Western blot. The colorectal cancer cell line HCT116 was irradiated with 0, 2, 4 and 6 Gy of X-rays. The expression of FOXD1 in each groups were detected by qRT-PCR and Western blot. HCT116 cells were transfected with FOXD1 siRNA and its negative control and termed as si-FOXD1 group and si-NC group. When these cells were irradiated with 4 Gy X-rays, they were termed as si-FOXD1+4 Gy group and si-NC+4 Gy group. Cell proliferation was detected with MTT method, cell survival fraction was measured with colony formation assay, and DNA-PK activity was detected by TECT DNA-PK kit. The siRNA-transfected colorectal cancer cells were inoculated into BALB/c nude mice to establish the xenograft model. After irradiation, the volume and quality of the subcutaneous transplanted tumors were measured every 5 days. Results The expression of FOXD1 mRNA and protein in colorectal cancer tissues was higher than that in adjacent normal tissues (t=5. 579, 4. 816, P<0. 05). The mRNA(t=5. 85-17. 62, P<0. 05)and protein(t=9. 04-11. 42, P<0. 05) expression of FOXD1 in different colorectal cancer cell lines was higher than that in colonic mucosa epithelial cell line NCM460. The expression of FOXD1 in colorectal cancer cells HCT116 was increased after radiation in a dose dependent manner(t=9. 13-44. 15, P<0. 05). Transfection of si-FOXD1 effectively inhibited the expression of FOXD1 (t=10. 51, P<0. 05), decreased proliferation (t=10. 41, P <0. 05), increased radiosensitivity with a radiosensitization ratio of 1. 797, and reduced the radiation-induced DNA-PK activity ( t = 6. 20, P < 0. 05 ) in colorectal cancer cells. After localized irradiation, the tumor volume and weight in nude mice transplanted with si-FOXD1 HCT116 cells were significantly smaller than those in HCT116 (t=11. 29, 3. 69, P<0. 05). Conclusions Knock-down of FOXD1 gene increases the radiosensitivity of colorectal cancer cells and inhibits the growth of colorectal cancer xenograft in nude mice, which provides a potential target gene in improving the effect of radiotherapy on colorectal cancer.

Clinical Observation of Small Dose of Octreotide for Preventing Hyperamylasemia and Acute Pancreatitis after Endoscopic Retrograde Cholangiopancreatography / 中国药房

OBJECTIVE:To observe clinical effects and safety of small dose of octreotide for preventing hyperamylasemia and acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).METHODS:One hundred and twenty ERCP pa tients were selected from our hospital during Oct.2014-Jan.2015 and then divided in to observation group and control group in accordance with random number table,with 60 cases in each group.Both groups were given Diazepam tablet 10 mg+Meperidine hydrochloride tablet 100 mg+Phenobarbital scopolamine tablet 2 tablets 0.5 h before surgery for sedation and analgesia,and routine acid suppression and anti-infective therapy.Observation group was additionally given Octreotide acetate injection 0.1 mg hypodermically and then given Octreotide acetate injection 0.1 mg immediately after surgery,8 h after surgery.The levels of serum amylase and blood glucose were observed in 2 groups,and the occurrence of postoperative complication and ADR were recorded.RESULTS:Before operation,there was no statistical significance in the levels of serum amylase and blood glucose between 2 groups (P＞ 0.05).After operation,the level of serum amylase in control group was significantly higher than in observation group,with statistical significance (P＜0.05).There was no statistical significance in blood glucose level between 2 groups after operation (P＞0.05).The incidence of hyperamylasemia and ADR in observation group was significantly lower than in control group,with statistical significance (P＜0.05),and there was no statistical significance in the incidence of acute pancreatitis between 2 groups after operation (P＞0.05).CONCLUSIONS:Small dose of octreotide can effectively reduce the level of serum amylase and the incidence of hyperamylasemia after ERCP with good safety.

Determination of fenticonazole in human plasma by HPLC-MS/MS and its application to pharmacokinetic studies / 药物分析学报

Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS), and simple protein precipitation by acetonitrile containing 2%acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges of fenticonazole were 5–1000 pg/mL and 0.1–20 ng/mL in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.

Hyperimmunoglobulin E syndrome in adult patients: a case report and literature review / 中华全科医师杂志

The clinical manifestations,laboratory test results,treatments and prognoses of 5 adult patients with hyperimmunoglobulin E syndrome (HIES) were retrospectively analysed.All 5 patients experienced disease onset within 1 year of birth and had recurrent multiple infections,all had recurrent rash and 4 had skeletal abnormalities.Recurrent infections lasted for a mean of 19.6 years and predominantly affected the skin and respiratory tract.Other manifestations included chronic otitis media,renal abscess and osteomyelitis.Two cases had skin abscess (methicillin-susceptible Staphylococcus aureus infection),which was alleviated after antibiotic treatment and abscess drainage.Two cases had respiratory tract infection and one case had a foot skin ulcer,and all symptoms improved after antibiotic treatment.HIES should be suspected when an adult patient experiences repeated infection since birth,particularly when skeletal abnormalities and a history of neonatal rash is also present.Early diagnosis facilitates targeted anti-infection therapy,leading to earlier remission and an improved prognosis.

Programmed cell death 4 enhances radiosensitivity of pancreatic cancer cells / 中华放射医学与防护杂志

Objective To investigate the effect and mechanism of programmed cell death 4 ( PDCD4 ) on radiosensitivity of pancreatic cancer cells. Methods Pancreatic cancer tissues and corresponding adjacent tissues were collected, the expression level of PDCD4 was detected by RT-PCR and Western blot. Human pancreatic cancer cells Sw1990 were transfected with PDCD4 overexpression vector ( group pIRES2-PDCD4 ) , empty vector ( pIRES2 group ) , and treated with transfection reagent, respectively. The expression level of PDCD4 was detected by RT-PCR and Western blot. After radiation treatment, cell apoptosis was detected by flow cytometry, cell survival was detected by clone assay, and the expression levels ofβ-catenin, c-myc and Cleaved Caspase-3 were detected by Western blot. Results The expression of PDCD4 mRNA and protein in pancreatic cancer tissues was significantly lower than that in adjacent tissues (t=4. 869, 9. 208, P<0. 05). The expression of PDCD4 mRNA and protein in pIRES2-PDCD4 group was significantly lower than that in the non-transfection group ( t =9. 074, 18. 927, P <0. 05). After radiation, the apoptosis rate and Cleaved Caspase-3 level in the pIRES2-PDCD4 group were significantly higher than those in the non-transfection group (t =3. 670, 4. 086, P <0. 05), while the expression levels of β-catenin and c-myc in the cells were significantly lower than those in the non-transfection group (t =9. 242, 17. 644, P <0. 05). The radiosensitivity of pIRES2-PDCD4 group was higher than that of non-transfection group, and the sensitization ratio was 1. 843. Conclusions PDCD4 can increase radiosensitivity and promote apoptosis of pancreatic cancer cells, to which the Wnt signaling pathway may be related.

Blockade of CLC-3 chloride channel inhibited the viability and invasion of colorectal cancer cells / 中国肿瘤临床

Objective:To examine the expression of CLC-3 in colorectal tissues and the effect of CLC-3 on the viability and invasion of colorectal cancer (CRC) SW480 and SW620 cells. Methods:The mRNA levels of CLC-3 in CRC cell lines were determined by RT-PCR. CLC-3 expression was inhibited by adding DIDS or NPPB to the CRC cells. Subsequently, cell viability and invasion were assessed by CCK-8 assay and Transwell assay, respectively. In addition, the effects of DIDS and NPPB on the Wnt orβ-catenin signaling pathways were de-termined by Western blot analysis. Results:The mRNA level of CLC-3 was remarkably increased in the CRC tissues compared with that in normal colorectal tissues (P<0.05) and was positively correlated with the T stage of CRC. The blockade of CLC-3 inhibited the viability and invasion of CRC cells (P<0.05). The expression ofβ-catenin, C-myc, cyclin D1, Ki-67, and survivin were evidently reduced by the in-hibition of CLC-3 (P<0.05). Conclusion:The inhibition of CLC-3 decreases the cell viability and invasion of CRC cells by reducing the ex-pression of the proteins related to the Wnt orβ-catenin signaling pathway.

Investigation of Pharmacokinetics and Bioequivalence of Mecobalamin in Healthy Volunteers by Chemilu-minescent Microparticle Immunoassay / 中国药师

Objective:To develop a chemiluminescent microparticle immunoassay ( CMIA) method for the determination of meco-balamin in human serum to investigate the pharmacokinetics and bioequivalence of mecobalamin. Methods:A single oral dose of two kinds of mecobalamin was given to 19 healthy volunteers in a randomized three-period crossover study. The concentrations of mecobal-amin in serum were assayed by CMIA, the main pharmacokinetic parameters were analyzed by DAS 3. 0 software, and the bioequiva-lence was evaluated. Results: The main pharmacokinetic parameters of test and reference mecobalamin tablets were as follows: tmax were (4.2 ±1.9)h and (4.4 ±2.4)h,Cmax were (322.0 ±145.4) ng·L-1 and (282.2 ±108.1) ng·L-1,t1/2 were (19.2 ±5.3) h and (20.0 ±6.3)h,AUC0-72 were (6 769.1 ±2 169.4) ng·h·L-1 and (6 400.6 ±1 921.5) ng·h·L-1. F(0-72) and F(0-∞) of the test tablets was 105. 9% ± 13. 2% and 104. 9% ± 12. 6%,respectively. Conclusion:The method is simple and precise. The two tablets are bioequivalent.

Q fever endocarditis: a report of four cases and literature review / 中华内科杂志

Objective To improve the diagnosis and treatment of Q fever endocarditis.Methods From 2008 to 2013,four cases of Q fever endocarditis were diagnosed in Peking Union Medical College Hospital.Clinical features,laboratory test,management and prognosis were analyzed with literature review.Result All four cases had long period of fever and heart murmur.Two patients represented with respiratory symptom and one with non-specific rash.General laboratory tests including complete blood cell count,ESR,C-reactive protein(CRP),liver function and radiology of lung did not show specific abnormalities.Signs of endocarditis were shown by ultrasound and important for diagnosis.Repeated blood culture was negative.All of the diagnoses were confirmed by serum antibody detection and the patients recovered well with treatment based on doxycycline or minocycline.Conclusions Endocarditis is the most common form of chronic Q fever,which is easily misdiagnosed because its blood culture is negative and may accompanied with varied manifestation such as pneumonia and liver injury.For the patients with chronic fever and blood culture negative endocarditis,chronic Q fever should be considered as differential diagnosis.The confirmatory method for diagnosis is serum antibody detection.Early and sufficient treatment may improve the prognosis.

Clinical characteristics of 12 cases of chronic active Epstein-Barr virus infection / 中华全科医师杂志

The medical records of all 12 patients diagnosed as chronic active Epstein-Barr virus (CAEBV) infection at our hospital were analyzed retrospectively.There were 7 males and 5 females with a median onset age of 28 years.CAEBV was characterized by fever,splenomegaly,hepatomegaly and lymphadenopathy,etc.The abnormalities of laboratory examination included liver dysfunction,thrombocytopenia,anemia and leucopenia.EBV-DNA detected by real-time polymerase chain reaction was (1.7 × 103-3.5 × 107) copies/μg DNA in peripheral blood mononuclear cell.Among them,the outcomes were death (n =5),lost to follow-up (n =2) and T cell lymphoma (n =1).It is necessary to improve our awareness of CAEBV infection because of its poor prognosis and high mortality.

Chromatographic fingerprint of Dipsacus asper and analysis by HPLC-MS / 中国中药杂志

A high performance liquid chromatography (HPLC) method was developed for fingerprint of Dipsacus asper. Analysis were carried out on a Zorbax C-18 column by gradient elution using 0.1% phosphoric acid and acetonitrile as the mobile phases. The column was maintained at 25 degrees C, the flow rate was 1 mL x min(-1), and the detection wavelength was set at 205 nm. Asperosaponin VI was selected as reference compound, Seventeen common peaks were selected, and the fingerprint with good precision, stability and repeatability was successfully used to evaluate quality of 24 batches of crude extracts of D. asper. Chemical characteristics of D. asper was analyzed by DAD detection and HPLC-MS techniques with an ESI source. The quasi-molecular ions of compounds in both negative and positive modes were observed for molecule mass information of 33 compounds, and the potential structures of 10 characteristic components were identified by study on the mass spectra of compounds and comparing with reference data and some of standards. The results indicate the HPLC fingerprint of D. asper will show more characters through identification of component structures using an HPLC-ESI-MS method, and will control the quality of D. asper more effectively and reasonable.

Analysis on relevant factors for hepatitis B virus-associated glomerulonephritis / 中华肾脏病杂志

Objective To retrospectively evaluate the relevant factors for hepatitis B virus-associated glomerulonephritis (HBV-GN).Methods A total of 86 patients with pathologyproven HBV-GN and 135 HBV carriers with non-HBV-GN were included in this retrospective casecontrol study.Logistic regression analysis was used to detect the relevant factors for HBV-GN.Results On univariate analysis,the factors associated with HBV-GN were as follows: male (OR 2.79,95%CI 1.48-5.25,P=0.001),HBeAg positivity (OR 2.60,95%CI 1.49-4.53,P=0.001),HBV replication (OR 3.63,95%CI 1.80-7.33,P＜0.01),liver cirrhosis (OR 4.58,95%CI 1.41-14.91,P=0.011),and elevated alanine aminotransferase (ALT) (OR 2.53,95%CI 1.42-4.51,P=0.002).On multivariate analysis,the associations remained significant for male (OR 2.21,95%CI 1.12-4.33,P=0.022),HBV replication (OR 2.77,95%CI 1.28-5.97,P=0.01),liver cirrhosis (0R 4.55,95%CI 1.29-16.10,P=0.019) and elevated ALT (OR 1.96,95%CI 1.04-3.69,P=0.037).Compared with HBV-associated IgA nephritis (HBV-IgAN) in multivariate model,HBV-associated membranous nephropathy (HBV-MN) or membranoproliferative glomerulonephritis (HBV-MPGN) was significantly associated with male (OR 6.51,95%CI 1.76-24.11,P=0.005) and HBV replication (OR 7.22,95%CI 1.68-30.97,P=0.008).Conclusions Male,HBV replication,liver cirrhosis and elevated ALT may be predictive factors for HBV-GN.Compared with HBV-IgAN,HBV-MN or HBV-MPGN is significantly associated with male and HBV replication.