[Mycobacterium xenopi pulmonary disease:report of 3 cases and literature review].

Objective: To analyze the clinical manifestations, radiographic characteristics and prognosis of Mycobacterium xenopi pulmonary disease, in order to improve diagnosis and treatment of the disease. Methods: Using "Mycobacterium xenopi, pulmonary disease" as the search term, from February 15, 2007 to February 21, 2021, a total of 1 264 cases were retrieved in the PubMed database. In the Wanfang database, using "Mycobacterium xenopi, pulmonary disease" as the search term, from February 15, 2007 to February 21, 2021, no related document was retrieved. In the CNKI database, "Mycobacterium xenopi, pulmonary disease" was used as the search term, and one relevant case report was retrieved, but did not meet the diagnostic criteria of Mycobacterium xenopi pulmonary disease issued by American Thoracic Society in 2007. The 1 264 cases from the literature and 3 cases of our institution were used for review. Results: Our 3 cases were elderly males complaining of cough and expectoration, and had underlying lung diseases. The imaging examination showed cavitary lesions. All of them had positive sputum smear for acid-fast bacillus and negative Xpert MTB/RIF examination. Mycobacterium xenopi was isolated at least 2 times from sputum samples. Although prescribed with chemotherapy, case 1 and case 2 died 4 years and 2 years later, respectively, after the diagnosis. Case 3 got sputum conversion, symptom improvement and radiographic responses after 30-month chemotherapy. Conclusions: The clinical manifestations of Mycobacterium xenopi pulmonary disease are atypical. For patients with positive sputum smear for acid-fast bacillus and negative Xpert MTB/RIF examination and conventional mycobacterial culture, Mycobacterium xenopi pulmonary disease should be considered. The disease deserves further attention from clinicians due to poor prognosis.

[In vitro evaluation of the antibacterial activity of nemonoxacin against Mycobacterium tuberculosis, Mycobacterium intracellulare and Mycobacterium abscessus].

Objective: To test the in vitro antibacterial activity of nemonoxacin against clinically isolates of Mycobacterium tuberculosis complex(MTBC), Mycobacterium intracellulare(MI) and Mycobacterium abscessus(MA). Methods: Totally 128, 80 and 50 isolates of MTBC, M.intracellulare and M.abscessus were tested, respectively. The minimum inhibitory concentrations (MICs) of nemonoxacin and levofloxacin against the strains of the three most frequently isolated mycobacterium species were measured by double dilution method with micro-well plate. Results: The MICs of 104(81.2%) strains of MTBC isolates against levofloxacin were ≤ 1 µg/ml. Whereas 112 (87.5%) strains of MTBC isolates had MICs against nemonoxacin than>1 µg/ml, furthermore, the MICs of 88(68.8%)strains of MTBC isolates against nemonoxacin were≥4 µg/ml. The median MIC of M. intracellulare isolates against levofloxacin and nenofloxacin were 16 and 32 µg/ml, separately, while were 16 µg/ml and 8 µg/ml for M. abscessus, respectively. The ratios of nemonoxacin MIC/levofloxacin MIC of M. abscessus were between 0.125-1.000. Conclusions: Nemonoxacin presented weaker inhibitory activity than levofloxacin against M. tuberculosis, whereas it had better activity than levofloxacin against M. abscessus.

Efficacy of supplemented Er-xian decoction combined with acupoint application for poor ovarian response.

This study aims to observe the efficacy of supplemented Er-xian decoction combined with acupoint application in treating poor ovarian response (POR). This study was a randomized controlled trial. A total of 80 patients, who were treated in the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from January 2016 to December 2017, were divided into two groups by tables of random numbers: experimental group (n = 40), and control group (n = 40). In the experimental group, patients orally received supplemented Er-xian decoction with acupoint application. In the control group, a Kuntai capsule was administered according to the course of treatment. The therapeutic effects in the two groups were observed and compared. In the experimental group, the total effective rate was 90%, the cure rate was 15% (six patients), the markedly effective rate was 35% (14 patients), the effective rate was 40% (16 patients), and the ineffective rate was 10% (four patients). In the control group, the total effective rate was 50%, the cure rate was 5% (two patients), the markedly effective rate was 15% (six patients), the effective rate was 30% (12 patients), and the ineffective rate was 50% (20 patients). The differences were statistically significant (P > 0.05). Definite efficacy was observed when a poor ovarian response was treated by supplemented Er-xian decoction combined with acupoint application. Improvements in perimenopausal symptoms, menstruation conditions, hormone levels, inhibin B (INHB), and antral follicle count (AFC) were markedly better in the experimental group than in the control group. In addition, the treatment was safe and had few side effects.

Efficacy and safety of intra-articular injection of tropomyosin receptor kinase A inhibitor in painful knee osteoarthritis: a randomized, double-blind and placebo-controlled study.

OBJECTIVE: This trial evaluated the efficacy and safety of GZ389988A, a tropomyosin receptor kinase A (TrkA) inhibitor, in subjects with painful knee osteoarthritis (OA). METHOD: In this single center, double-blind, placebo-controlled and randomized trial, 104 subjects with moderate-to-severe knee OA pain were enrolled to receive a single intra-articular (IA) injection of either GZ389988A or placebo. Efficacy measures were assessed over 12 weeks and included walking pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] A1), overall knee pain, WOMAC A, B, C and total score, Patient Global Impression of Change (PGIC), OMERACT-OARSI responder rate and rescue medication use. Adverse events (AEs) were monitored up to 24 weeks. RESULTS: The primary efficacy endpoint was met with a between-group difference of -7.49 (VAS 0-100) on WOMAC A1 changes over 4 weeks (P < 0.05 favoring GZ389988A). The secondary outcome on WOMAC A1 changes over 12 weeks had a between-group difference of -6.78 (P = 0.064). Among weekly assessments, statistically significant greater improvement in the GZ389988A group was observed in WOMAC A1, overall knee pain and/or WOMAC A at weeks 2-5. Although not statistically significant, improvements over placebo on pain and WOMAC C persisted over 12 weeks. Greater AE incidence was observed in the GZ389988A group including transient and self-limited injection joint inflammatory reactions with a spike of acetaminophen intake within the first week post-injection. CONCLUSION: IA injection of TrkA inhibitor GZ389988A in knee OA subjects reduced pain with a numerically functional gain and an acceptable safety profile. (ClinicalTrials.gov, NCT02845271).

[Incremental cost-effectiveness of the second Xpert MTB/RIF assay for detection of Mycobacterium tuberculosis].

Objective: To study the incremental cost-effectiveness of the second Xpert assay in detection of Mycobacterium tuberculosis (Mtb) and rifampicin (RIF) resistance. Methods: We continuously collected 2 896 specimens from suspected tuberculosis patients who had undergone 2 Xpert tests in a week from March 2015 to March 2018, including 2 402 suspected tuberculosis patients with 1 523 males and 879 females, with an average age of 50 years. Among them, 2 144 specimens of sputum and 258 cases of bronchoalveolar lavage fluid were collected. We also enrolled 494 patients with suspected extrapulmonary tuberculosis, 318 males and 176 females, with an average age of 42 years. Among them, 157 pleural effusion specimens, 106 cerebrospinal fluid specimens, 34 urine specimens and 197 pus specimens were collected. All specimens were subjected to two Xpert tests, smear microscopy, liquid rapid culture (BACTEC MGIT 960), and positively cultured bacteria were tested for drug susceptibility. Results: Among the 2 896 specimens from suspected tuberculosis patients, either one of the two Xpert test results was positive (including both tests were positive, the same below) in 1 639 patients, and 1 502 (91.6%) were positive in the first Xpert tests. The additional 137 (8.4%) test results were positive in the second tests. According to the smear test results, all specimens were divided into the smear negative group and the smear positive group. The second Xpert test was significantly higher than the smear-positive group (14.86%, 3.2%, P<0.001), and the extrapulmonary tuberculosis group was higher than the tuberculosis group (11.2%, 8.0%, P=0.12).Of the susceptibility test results, a total of 371 were rifampicin-resistant specimens. The first Xpert detected 91.4% (339/371), and the second Xpert detected the additional 8.1% (30/371).The cost increase of the second test was very significant. Tests were calculated at 650 yuan per time, the tuberculosis group was 1 184 yuan and 13 696 yuan(P<0.001); the extrapulmonary tuberculosis group was 1 755 yuan and 13 961 yuan(P<0.001). In the test of specimens of tuberculosis and extrapulmonary tuberculosis, the smear-negative specimen cost increase of the second Xpert test was lower than that of the smear-positive specimen. Conclusion: The second xpert test showed significant value-added cost-effectiveness in the diagnosis of tuberculosis.

Evaluating the use of intra-articular injections as a treatment for painful hip osteoarthritis: a randomized, double-blind, multicenter, parallel-group study comparing a single 6-mL injection of hylan G-F 20 with saline.

OBJECTIVE: Hip osteoarthritis (OA) is difficult to treat. Steroid injections reduce pain with short duration. With widespread adoption of office-based, image-guided injections, hyaluronic acid is a potentially relevant therapy. In the largest clinical trial to-date, we compared safety/efficacy of a single, 6-mL image-guided injection of hylan G-F 20 to saline in painful hip OA. METHOD: 357 patients were enrolled in a multicenter, double-blind, randomized saline placebo- controlled trial. Subjects were ≥35 years of age, with painful (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]-A1:5.0-8.0; numeric rating scale [NRS]: 0-10) mild-to-moderate hip OA (Kellgren-Lawrence grade II/III) and minimal contralateral hip pain (WOMAC-A1 < 4). Outcome measures included "pain on walking" (WOMAC-A1 and -A), Patient Global Self-Assessment (PTGA), WOMAC-A1 responder rate (+≥2 points on NRS), and adverse events (AEs) over 26 weeks. RESULTS: 357 patients (hylan G-F 20 single:182; saline:175) were enrolled. Both groups demonstrated significant pain improvement from baseline over 26 weeks (P < 0.0001); saline-induced pain reduction was a remarkable 35%. WOMAC-A and PTGA scores also significantly improved (P < 0.0001). No statistically significant difference was observed between groups in WOMAC-A1 scores (hylan G-F 20 single:-2.19 ± 0.16; saline:-2.26 ± 0.17) or WOMAC-A1 responders (41-52%). Treatment-related AE rates at target hip were similar (hylan G-F 20 single:23 patients [12.8%]; saline:12 [7.0%]). Posthoc analysis found, despite protocol requirements, many patients had psychological (31%) or potential neuropathic pain (27.5%) conditions. CONCLUSION: A single 6-mL hylan G-F 20 injection or saline for painful hip OA resulted in similar, statistically significant/clinically relevant pain and function improvements up to 6 months following injection; no differences between hylan G-F 20 and saline placebo were observed.

[Antimicrobial susceptibility and genotyping of Mycobacterium intracellulare].

Objective: To investigate the antimicrobial susceptibility and genotyping of Mycobacterium intracellulare. Methods: A total of 150 M. intracellulare isolates were collected. The susceptibility against 15 antimicrobial agents widely used for treatment of non-tuberculosis mycobacteria (NTM) infections, was tested by broth microdilution assay. Variable number of tandem repeats (VNTR) assay was also performed using the 16-loci genotyping method. Results: The drug susceptibility test revealed that clarithromycin (97.3%, 146/150), moxifloxacin (94.0%, 141/150) and amikacin (90.0%, 135/150) had the best antimicrobial activities in vitro against the M. intracellulare isolates. Secondly, 75.3%(113/150), 64.0%(96/150), 52.7%(79/150) and 8.7%(13/150) of the strains were susceptible to rifampicin, linezolid, capreomycin, and ethambutol, respectively. The MIC(50) and MIC(90) values of the 3 injectable anti-tuberculosis drugs were as follows: amikacin 4 mg/L and 16 mg/L, streptomycin 4 mg/L and 16 mg/L, capreomycin 8 mg/L and 16 mg/L. The MIC(50) and MIC(90) values of the 5 different fluoroquinolones were 0.5 mg/L and 2 mg/L for moxifloxacin , 1 mg/L and 8 mg/L for ciprofloxacin, 1 mg/L and 8ug/ml for levofloxacin, 2 mg/L and 16 mg/L for antoflolxacin, 2 mg/L and 16 mg/L for ofloxacin. The Hunter-Gaston Discriminatory Index (HGDI) value for the 16-loci VNTR typing of M. intracellulare isolates was 0.994. VNTR differentiated the 150 isolates into 21 clusters and acquired a total of 121 unique patterns. Drug resistance profile was not independently associated with cluster strains. Conclusions: Clarithromycin, moxifloxacin and amikacin had the best antimicrobial activities in vitro against M. intracellulare isolates. The 16-loci VNTR typing revealed a highly discriminatory power and drug resistance profile was not independently associated with cluster strains.

Diverse polarization bi-stability in ferroelectric tunnel junctions due to the effects of the electrode and strain: an ab initio study.

Both electrodes and substrates are factors of great significance for the performance of ferroelectric tunnel junctions (FTJs) in designing functional nanodevices. To provide a comprehensive view on the polarization stability in FTJs due to the effects of an electrode and a substrate misfit strain, in this work we calculated more than 1000 FTJ structures by utilizing an ab initio density functional theory (DFT) method, via changing the symmetry of the FTJ structure (i.e., both asymmetric and symmetric FTJs), electrodes (including Au, Ag, Cu, Pt, Co, Fe, and SrRuO3), barrier thickness (ranging from 2 to 10 unit cells), polarization direction (both positive and negative polarizations) and epitaxial strain (i.e., -3%, -2.5%, -2%, -1.5% and -1%) as variables. This shows that the FTJs can exhibit quite diverse polarization bi-stability due to the combined effect of the electrode and strain control, which indicates diverse performance of the FTJs modulated by the electrode and strain. In particular, the polarization-mediated electrostatic potential in the barriers with different electrodes forecasts an electrode-tailored tunnel electroresistance effect. Our study provides guidance on the practical applications of FTJs with regard to the selection of electrodes and substrates.

Intra-articular onabotulinumtoxinA in osteoarthritis knee pain: effect on human mechanistic pain biomarkers and clinical pain.

OBJECTIVES: OnabotulinumtoxinA (onabotA) attenuates peripheral nociceptive transduction and consequently neuronal firing. The aim of this mechanistic study was to evaluate the effect of intra-articular (IA) onabotA in patients with painful knee osteoarthritis (OA). METHOD: We conducted a double-blind, randomized, placebo-controlled, 12-week trial using a single ultrasound-guided IA injection of onabotA (200 U). Patients (N = 121) were randomized to receive onabotA (n = 61) or placebo (n = 60). Mechanistic pain biomarkers and clinical outcomes were used for profiling the effect. The biomarkers were pressure pain thresholds (PPTs) from the knee joint (localized sensitization) and extra-articular sites (widespread sensitization), and wind-up pain (central sensitization). Clinical assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), average daily pain (ADP), patient global impression of change (GIC), and rescue medication. The painDETECT questionnaire (PD-Q) was used for subgrouping patients (nociceptive, neuropathic, and mixed/uncertain). RESULTS: The nociceptive and non-nociceptive groups were identical with respect to all baseline data. No significant differences in clinical efficacy parameters were found between onabotA and placebo in the entire population. The nociceptive group showed significant improvement after IA onabotA at week 8 for all WOMAC outcomes, ADP at weeks 9 and 10, and patient GIC at week 12, and significant reduction in rescue medication counts within each 14-day period at weeks 9 and 10. After 4, 8, and 12 weeks, significant correlations were obtained in the onabotA group between ADP (both the entire group and the nociceptive group) and various sensitization parameters. The nociceptive group showed pronounced effects on widespread sensitization. CONCLUSIONS: Intra-articular onabotA given to patients with nociceptive knee OA reduced pain sensitization together with improvement in pain and function.

Sensititre® MYCOTB MIC plate for drug susceptibility testing of Mycobacterium tuberculosis complex isolates.

SETTING: National Tuberculosis Clinical Laboratory, China. OBJECTIVE: To evaluate the accuracy and feasibility of the MYCOTB MIC plate in anti-tuberculosis drug susceptibility testing. DESIGN: MYCOTB testing of Mycobacterium tuberculosis isolates, the Löwenstein-Jensen (LJ) proportion method and the resurazine microtitre assay (REMA), which is extensively used for in-house assay for minimal inhibition concentration (MIC) testing, were performed simultaneously for comparison. A total of 126 clinical isolates were tested using both MYCOTB and the LJ proportion method against 12 anti-tuberculosis drugs; 80 were also tested using REMA. RESULTS: Categorical agreement between MYCOTB and the LJ proportion method was 99.2% for rifampicin, ofloxacin, amikacin, kanamycin and cycloserine, and 98.4% for isoniazid and para-aminosalicylic acid; ethambutol (EMB) had the lowest agreement (86.5%). The overall categorical agreement between MYCOTB and REMA ranged between 98.8% and 100%. MYCOTB outcomes, interpreted on day 10 and 21, were stable for all drugs except EMB. CONCLUSION: MYCOTB is a rapid, convenient, quantitative and accurate method for testing both first- and second-line anti-tuberculosis drugs.

Diverse interface effects on ferroelectricity and magnetoelectric coupling in asymmetric multiferroic tunnel junctions: the role of the interfacial bonding structure.

Interface and size effects on electric/magnetic orders and magnetoelectric coupling are vital in the modern application of quantum-size functional devices based on multiferroic tunnel junctions. In order to give a comprehensive study of the interface and size effects, the properties of a typical asymmetric multiferroic tunnel junction, i.e., Fe/BaTiO3/Co, have been calculated using the first-principles simulations. Most importantly, all of the eight possible structures with four combinations of electrode/ferroelectric interfaces (i.e., Fe/BaO, Fe/TiO2, Co/BaO and Co/TiO2) and a series of barrier thicknesses have been taken into account. In this work, the equilibrium configurations, polarization, charge density, spin density and magnetic moments, etc., have been completely simulated and comprehensively analyzed. It is found that the ferroelectric stability is determined as a competition outcome of the strength of short-range chemical bondings and long-range depolarization/built-in fields. M/BaO (M = magnetic metal) terminations show an extraordinary enhancement of local polarization near the interface and increase the critical thickness of ferroelectricity. The bistability of polarization is well kept at the M/TiO2 interface. At the same time, the induced magnetic moment on atoms at the interfaces is rather localized and dominated by the local interfacial configuration. Reversing electric polarization can switch the induced magnetic moments, wherein atoms in M-O-Ti and M-Ti-O chains show preference for being magnetized. In addition, the difference between the sum of the interfacial magnetic moments is also enlarged with the increase of the barrier thickness. Our study provides a comprehensive and detailed reference to the manipulation and utilization of the interface, size and magnetoelectric effects in asymmetric multiferroic tunnel junctions.

Reduced toxicity with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy compared with conventional two-dimensional radiotherapy for esophageal squamous cell carcinoma: a secondary analysis of data from four prospective clinical trials.

We conducted a retrospective analysis to assess the toxicity and long-term survival of esophageal squamous cell carcinoma patients treated with three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) versus conventional two-dimensional radiotherapy (2DRT). All data in the present study were based on four prospective clinical trials conducted at our institution from 1996 to 2004 and included 308 esophageal squamous cell carcinoma patients treated with 2DRT or 3DCRT/IMRT. Based on the inclusion and exclusion criteria, 254 patients were included in the analysis. Of these patients, 158 were treated with 2DRT, whereas 96 were treated with 3DCRT/IMRT. The rates of ≥Grade3 acute toxicity of the esophagus and lung were 11.5% versus 28.5% (P = 0.002) and 5.2% versus 10.8% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The incidences of ≥Grade 3 late toxicity of the esophagus and lungs were 3.1% versus 10.7% (P = 0.028) and 3.1% versus 5.7% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The 1-year, 3-year and 5-year estimated overall survival rates were 81%, 38% and 34% in the 3DCRT/IMRT group and 79%, 44% and 31% in the 2DRT group, respectively (P = 0.628). The 1-year, 3-year and 5-year local control rates were 88%, 71% and 66% in the 3DCRT/IMRT group and 84%, 66% and 60% in the 2DRT group, respectively (P = 0.412). Fewer incidences of acute and late toxicities were observed in esophageal squamous cell carcinoma patients treated with 3DCRT/IMRT compared with those treated with 2DRT. No significant survival benefit was observed with the use of 3DCRT/IMRT.

OARSI Clinical Trials Recommendations: Design, conduct, and reporting of clinical trials for knee osteoarthritis.

The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After the members voted we calculated the median score among the nine members of the working group who completed the score. The document includes 25 recommendations regarding randomization, blocking and stratification, blinding, enhancing accuracy of patient-reported outcomes (PRO), selecting a study population and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.

Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

BACKGROUND: Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. METHODS: Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. RESULTS: The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (<9 %). No new safety signals were reported. Objective response rate in 195 evaluable Chinese patients was 68.8 %, including four complete responses (2.1 %). Time to disease progression (TTP) and overall survival were 8.8 and 18.5 months, respectively. CONCLUSIONS: The safety and efficacy of first-line bevacizumab-based treatment in Chinese population with advanced NS-NSCLC are consistent with those in previous studies as well as in Asian subgroup population from SAiL study. No new safety signals were reported.

First proficiency testing of second-line anti-tuberculosis drug susceptibility testing in 12 provinces of China.

OBJECTIVE: To evaluate the performance of drug susceptibility testing (DST) against the main second-line (SL) anti-tuberculosis drugs in tuberculosis (TB) laboratories in China. METHOD: The supranational TB reference laboratory issued 30 Mycobacterium tuberculosis isolates to the participating laboratories. Each participating laboratory performed DST against kanamycin (KM), amikacin (AMK), capreomycin (CPM) and ofloxacin (OFX) using the proportion method in Löwenstein-Jensen medium per World Health Organization recommendations. Reported results were checked and compared with the judicial results. RESULT: The main performance indicators for the four anti-tuberculosis drugs evaluated (KM, AMK, CPM, OFX) were as follows: accordance rates: 91.62%, 99.16%, 96.93% and 96.37%; reproducibility: 99.16%, 99.16%, 94.96% and 94.12%; specificity: 99.12%, 99.64%, 98.00% and 98.41%; sensitivity: 78.03%, 97.62%, 94.44% and 91.51%. The accordance rates and sensitivity values of the four drugs showed statistically significant differences, while specificities showed no significant differences. CONCLUSION: Eight (66.7%) participating laboratories met the set requirement criteria; however, DST in four (33.3%) laboratories requires greater attention. Of the four drugs tested, the results for KM were lower than those for the other drugs. External quality assessment can lead to effective evaluation of laboratory performance in SL DST.

Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study.

INTRODUCTION: This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives. METHODS: Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500 mg/m(2); 107 randomized; 106 treated) or docetaxel (75 mg/m(2); 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded. RESULTS: The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P>0.025 (efficacy retained=97.9% [95% CLs: 47.1, 141.9]; P=0.0276), in the combined population (pemetrexed: n=390, docetaxel: n=392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P=0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n=107, docetaxel: n=104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P=0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P=0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P=0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P=0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P=0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients). CONCLUSION: The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274.

Genotyping and drug resistance patterns of Mycobacterium tuberculosis strains in five provinces of China.

OBJECTIVE: To evaluate the distribution of the Mycobacterium tuberculosis Beijing genotype and the association of the genotype with drug-resistant M. tuberculosis strains in five provinces in China. DESIGN: M. tuberculosis strains (n = 158) isolated from five provinces of China were subjected to insertion sequence 6110 restriction fragment length polymorphism (RFLP), spoligotyping and mycobacterial interspersed repetitive units (MIRU) analyses. The prevalence of the Beijing genotype strains in each province was determined and compared. The proportion method was used to test the drug susceptibility of all strains. RESULT: Of the 158 strains, 123 (77.8%) were identified as the Beijing genotype by RFLP and spoligotyping. Nearly all the strains (n = 152, 96.2%) were grouped into 14 shared spoligotypes. Six other spoligotypes were unique to China. The prevalence of the Beijing genotype was significantly higher in the interior than in coastal areas (P < 0.001, OR 5.4, 95%CI 2.3-12.7). Resistance to rifampicin (RMP) was associated with the Beijing strain (P = 0.05, OR 3.7, 95%CI 1.2-11.1). CONCLUSION: The M. tuberculosis Beijing genotype varies in prevalence in different regions of China and is solely associated with RMP resistance.

Involvement of mitogen-activated protein kinase activation in cyclooxygenase-2 and transforming growth factor-ß production in alveolar macrophage from chronic bronchitis rats.

OBJECTIVE: Lipopolysaccharides (LPS) activates several signaling pathways in macrophages including mitogen-activated protein kinases (MAPK). Previous studies have investigated effect of LPS on MAPK activation in macrophage of normal rats. In the current study, we investigated the effect of LPS exposure on activation of MAPK in alveolar macrophage (AM) of chronic bronchitis (CB) rats and researched the corresponding cyclooxygenase-2 (COX-2), prostaglandins-2 (PGE(2)) and transforming growth factor- ß (TGF-ß) production and their MAPK signal pathways. METHODS: CB model was established by injection of Bacillus Calmette-Guerin (BCG) and LPS in rats. Special inhibitors of p38, extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinases (JNK) MAPK signal pathways were used to determine the effect of MAPK activation on COX-2, PGE(2), TGF-ß production in AM of CB rats via RT-PCR, western blotting, radioimmunoassay and ELISA. KEY FINDINGS: Synthesis of PGE(2) from AM of CB rats was increased and suppressed by either PD98059 or SB203580. SB203580 and PD98059, (inhibitors of ERK and p38 MAPK), could significantly inhibit COX-2 mRNA and protein expression. Moreover, ERK and p38 MAPK had synergistic effect on COX-2 expression. Inhibitor of ERK MAPK signal transduction could inhibit TGF-ß expression in AM. CONCLUSION: These results demonstrated COX-2, PGE(2) and TGF-ß productions in AM of CB rats were significantly increased, which might be regulated by the different MAPK signaling pathway.

Effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf and MAPK signal transduction pathway on inducible nitric oxide synthase expression in alveolar macrophage of chronic bronchitis rats.

The goal of this study was to investigate the possible therapy mechanism of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. Leaf (TAL) in alveolar macrophage (AM) of chronic bronchitis (CB) rats. CB model was established by injection of bacillus calmette guein (BCG) plus lipopolisacharide (LPS) in rats. TAL significantly inhibited the increased NO concentration, iNOS expression and phosphorylation of p38 MAPK in alveolar macrophages (AMs) of CB rats. Using in vivo test, we found that SB203580, a p38 MAPK inhibitor, (10 muM) significantly inhibited inducible nitric oxide synthase (iNOS) mRNA expression in AM. This data indicate that TAL highly decreases excessive iNOS expression and NO induction, and p38 MAPK signal transduction participates in iNOS expression and NO induction in AM of CB rats. The effect of TAL on iNOS expression in AM may be related to its inhibition of p38 MAPK signal transduction.