[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Incidence and related factors of antiviral drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019].

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4+T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.

[Analysis of time for diagnosis of nontuberculous mycobacterial lung disease and its associated factors in a tuberculosis-designated hospital in Shanghai].

Objective: To investigate the pathogenic characteristics, bacteriological diagnosis time and its associated factors among patients with nontuberculous mycobacterial (NTM) lung disease in a large tuberculosis-designated hospital in Shanghai from 2020 to 2021, in order to improve diagnosis efficiency and formulate precision treatment. Methods: On the basis of the Tuberculosis Database in Shanghai Pulmonary Hospital, NTM patients diagnosed by the Department of Tuberculosis between January 2020 and December 2021 were screened. Demographic, clinical and bacterial information were retrospectively collected. Chi-square test, paired-sample nonparametric test and logistic regression model were used to analyze the factors associated with the diagnosis time of NTM lung disease. Results: A total of 294 patients with bacteriologically confirmed NTM lung disease were included in this study, 147 males and 147 females with a median age of 61(46, 69) years. Of them, 227 (77.2%) patients had comorbidity of bronchiectasis. Species identification results showed that Mycobacterium Avium-Intracellulare Complex was the main pathogen of NTM lung disease (56.1%), followed by Mycobacterium kansasii (19.0%) and Mycobacterium abscessus (15.3%). Species such as Mycobacterium xenopi and Mycobacterium malmoense were rarely identified, accounting for a total proportion of only 3.1%. Positive culture rates for sputum, bronchoalveolar lavage fluid and puncture fluid were 87.4%, 80.3% and 61.5%, respectively. Paired-sample analysis showed that the positive rate of sputum culture was significantly higher than that of smear microscopy (87.1% vs. 48.4%, P<0.01), while no statistical difference was observed between sputum and bronchoalveolar lavage fluid on positive culture rate (78.7% vs. 77.3%, P>0.05). Patients with cough or expectoration were observed with 4.04-fold (95%CI 1.80-9.05) or 2.95-fold (95%CI 1.34-6.52) higher probability of positive sputum culture, compared to those without. Regarding bronchoalveolar lavage fluid, female or patients with bronchiectasis had a 2.82-fold (95%CI 1.16-6.88) or 2.38-fold (95%CI 1.01-5.63) higher probability to achieve a positive culture. The median time to diagnosis of NTM lung disease was 32 (interquartile range: 26-42) days. The results of multivariable analysis showed that patients with symptom of expectoration (aOR=0.48, 95%CI 0.29-0.80) needed a shorter diagnosis time in comparison with patients without expectoration. With Mycobacterium Avium-Intracellulare Complex as a reference, lung disease caused by Mycobacterium abscessus needed shorter diagnosis time (aOR=0.43, 95%CI 0.21-0.88), whereas those caused by rare NTM species were observed to require a longer diagnosis time (aOR=8.31, 95%CI 1.01-68.6). Conclusion: The main pathogen causing NTM lung disease in Shanghai was Mycobacterium Avium-Intracellulare Complex. Sex, clinical symptoms and bronchiectasis had an impact on the positive rate of mycobacterial culture. The majority of patients in study hospital were timely diagnosed. Clinical symptoms and NTM species were associated with the bacteriological diagnosis time of NTM lung disease.

[A multicenter randomized controlled study of bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang in the treatment of patients newly diagnosed with Helicobacter pylori infection and dyspepsia].

Objective: To investigate the Helicobacter pylori (H. pylori) eradication rate and improvement of dyspepsia in patients who were newly diagnosed with H. pylori infection and dyspepsia and treated by bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang(JHWK). Methods: Patients who were newly diagnosed with dyspepsia and H. pylori infection and treated in 16 medical centers in China between December 1, 2017 and September 30, 2019 were randomly divided into two groups. The experimental group received bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days), followed by JHWK (30 days), and the course of treatment was 44 days in total. In the control group, the administration regimen was bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days). The main outcome measure was H. pylori eradication rate, while the secondary outcome measures were dyspepsia symptom changes and adverse events during the treatment and the 1st month after treatment. Results: A total of 1 054 patients were included in the study. There were 522 cases enrolled in the experimental group, including 224(42.91%) men and 298(57.09%) women, and the age was 53(26, 73) years old; 532 cases enrolled in the control group, including 221(41.54%) men and 311(58.46%) women, and the age was 46(22, 71) years old. Based on PP analysis, it was found that the H. pylori eradication rate in the experimental group was significantly higher than those in the control group (93.85% vs 87.88%, P=0.001). In the group of all enrolled patients, the symptom dyspepsia after H. pylori eradication was significantly improved compared with that before treatment [4(4, 7) vs 15(10, 22), P<0.001], so was the superior and middle abdominal pain [1(1, 4) vs 4(1, 8), P<0.001], the postprandial fullness [1(1, 4) vs 4(4, 9), P<0.001], the early satiety [1(1, 1) vs 4(1, 4), P<0.001], and the heartburn [1(1, 1) vs 1(1, 4), P<0.001]. The symptom dyspepsia after treatment was significantly improved compared with that before treatment in the experimental, the control groups, the successful and the unsuccessful H. pylori eradication groups. The superior and middle abdominal pain after treatment was signifcantly improved than that before treatment [1(1, 2) vs 1(1, 4), P<0.001], so were the postprandial fullness [1(1, 3) vs 1(1, 4), P=0.002] and the dyspepsia[4(4, 7) VS 7(4, 10), P<0.001]. There was no statistically significant difference in the incidence of adverse events between the experimental group and the control group (1.34% vs 0.38%, P=0.09). Conclusions: Compared with bismuth-containing quadruple therapy, bismuth-containing quadruple therapy followed by JHWK significantly improves the H. pylori eradication rate without increasing the incidence of adverse events. H. pylori eradication therapy can improve symptoms of patients with H. pylori infection and dyspepsia.

[Pepsin and bile acids detection in saliva for the diagnosis of gastroesophageal reflux disease].

Objective: To identify the value of the detection of pepsin and bile acids in saliva for the diagnosis of gastroesophageal reflux disease(GERD). Methods: From January 2018 to June 2019, 104 GERD patients and 43 healthy people in Guangdong Provincial People's Hospital were recruited. The 104 patients of GERD group were divided into four sub-groups, including esophageal symptoms GERD group, extraesophageal symptoms GERD group, anxiety or depression group, non-anxiety and non-depression group. Saliva was collected on waking in morning and 2 h after finishing lunch. The concentration of the total pepsin(TPP) and total bile acids(TBA) from saliva was detected by ELISA method. Receiver operating characteristics analysis was used to identify the sensitivity and specificity of the saliva pepsin and bile acids detection. Results: The concentration of TPP in morning waking samples and postprandial samples in the GERD group was 27.1(9.7,50.3) µg/L and 32.4(14.0,58.7) µg/L, the concentration of TBA in postprandial samples was (18.4±2.3)µmol/L, and these levels were significantly higher than that of the control group [7.0(5.1, 9.1) µg/L, 7.4(5.2, 9.4) µg/L, (12.6±5.0)µmol/L](P<0.01). The concentration of TBA in morning waking samples had no significant difference between these two groups(P>0.05). The concentration of TPP and TBA had no significant difference among the four GERD sub-groups(P>0.05).Pepsin in postprandial saliva samples had moderate diagnostic value for GERD, when the saliva pepsin concentration in postprandial samples was higher than 41.33 µg/L, it had a sensitivity of 82.8% and a specificity of 73.3%. The bile acids in saliva had no significant diagnostic value for GERD. Conclusions: Pepsin detection in saliva has a high level of sensitivity and specificity for diagnosing GERD. However, bile acids in saliva has no significant diagnostic value for GERD.

[Injury of small intestinal mucosa in rats induced by aspirin and clopidogrel and the protective effect of teprenone].

The purpose of this study was to investigate the injury of aspirin and clopidogrel on small intestinal mucosa in rats and the protective effect of teprenone. The study found that aspirin and clopidogrel could cause intestinal mucosal injury in rats, which was even worse with dual drugs. The mechanism of mucosal injury included free radical injury induced by aspirin and decreased synthesis of vascular endothelial growth factor (VEGF) by clopidogrel. Teprenone may repair intestinal mucosa via boosting VEGF level.

[Clinical characteristics and drug susceptibility test of nontuberculous mycobacterial lung disease].

Objective: To investigate the clinical characteristics and drug susceptibility test (DST) of patients infected with different nontuberculous mycobacteria (NTM). Methods: The patients with nontuberculous mycobacterial lung disease (NMLD) in Shanghai Pulmonary Hospital from March 2014 to March 2015 were studied retrospectively by analyzing the clinical characteristics, radiological features and DST results. A total of 201 NMLD patients [male 108, age(58±15) yrs] were enrolled into this study including 48 cases of M. Kansasii [male 13, age (52±16) yrs],46 cases of M. Abscess[male 46, age (57±16) yrs], 92 cases of M. Intracellulare [male 43, age (61±13) yrs], and 15 cases of M. Avium [male 6, age (67±10) yrs]. Clinical data were collected when the diagnosis was made and Chi-square test was used to compare the differences among 4 groups of patients. Bonferroni method was used for further pairwise comparisons. Results: There were significant differences among the 4 groups in the age(χ(2)=6.42, P<0.001) and the gender(χ(2)=49.18, P<0.001) of the patients. The history of bronchiectasis in the groups of M. Kansasii, M. Abscess, M. Intracellulare and M. Avium were 2/48, 31/46, 39/92 and 4/15 cases respectively(χ(2)=41.84, P<0.001). For the Gamma-interferon release assays (ELISA) (IGRA), the positive rate of IGRA in the groups of M. Kansasii, M. Abscess, M. Intracellulare and M. Avium were 83%(40/48), 30%(14/46), 23%(21/92) and 33% (5/15) respectively(χ(2)=50.96, P<0.001). The radiological features were significantly different in tree-in-bud(8/48, 35/46, 36/92 and 4/15 cases respectively, χ(2)=36.48, P<0.001), pleural thickness or mild effusion (21/48, 36/46, 69/92 and 7/15 cases, χ(2)=19.54, P<0.001), bronchiectasis (20/48, 39/46, 78/92 and 10/15 cases, P<0.001) and cavities (38/48, 21/46, 63/92 and 10/15 cases, χ(2)=12.38, P<0.001) among the 4 groups(M. Kansasii, M. Abscess, M. Intracellulare and M. Avium). The drug resistance rates of M. Kansasii to rifampin, ethambutanol and ofloxacin were 10%(5/48), 8%(4/48) and 15%(7/48) respectively; the resistance rates of M.Intracellulare to ethambutanol was 45%(41/92), and the resistance rates of M.Abscess were all over 80% to all anti-TB drugs. The results of pairwise comparisons showed that the male proportion(46/48) and IGRAs positive rate(40/48) of patients with M. Kansasii were higher than those of other groups, and the incidence of bronchiectasis(20/48) and pleural changes(21/48) was lower than those of other groups. The female ratio(33/46), history of bronchiectasis (31/46) and tree-in-bud sign of patients(35/46) with M. Abscess were higher than those of other groups. Conclusions: There were differences in the clinical manifestations and imaging features of 4 common NMLD diseases, which were helpful for clinical differentiation. The patients with M. Kansasii infection were mainly male, with a high IGRA positive rate and fewer lesions of bronchiectasis or pleural changes. Most of the patients with M. Abscess were female, with a previous history of bronchiectasis, and with most of the lesions showing tree-in-bud signs. The NTM species had a high rate of resistance to anti-TB drugs except M. Kansasii.

[The incidence, clinical characteristics and risk factors of upper gastrointestinal bleeding in patients taking dual antiplatelet therapy after percutaneous coronary intervention in south China].

OBJECTIVE: To investigate the incidence, clinical characteristics and risk factors of upper gastrointestinal bleeding (UGIB) in patients with acute coronary syndrome (ACS) who were administrated with aspirin and clopidogrel dual antiplatelet therapy after percutaneous coronary intervention (PCI). METHODS: ACS patients who had undergone PCI in the cardiovascular institute of Guangdong General Hospital from September 2009 to August 2014 were retrospectively enrolled.The incidence of UGIB and clinical characteristics of ACS patients on dual antiplatelet therapy for 1 year after PCI were analyzed.Risk factors of UGIB were screened in the cohort of patients and sex and age matched controls with ratio 1∶3. RESULTS: A total of 9 118 ACS patients had undergone PCI and UGIB occurred in 189 patients (2.07%, 189/9 118) from September 2009 to August 2014. UGIB patients with history over one year, gastrointestinal tumors or varices or negative endoscopy were excluded.Thus the revised incidence of UGIB occurred was 0.61% in 56 patients (0.61%, 56/9 118) and appeared to decline year by year.Most patients (91.07%, 51/56) had melena or stool occult blood positive (OB+ ), while others had bloody stool or haematemesis.Most UGIB were ulcer-related which was proved by endoscopy, accounting for 67.86% (38/56). There were 24 cases with duodenal ulcer, 13 with gastric ulcer and 1 with complex ulcer, while others were gastric erosion, gastritis and duodenitis.The risk factors of UGIB were previous history of peptic ulcer (P<0.01) and renal impairment (P<0.01). On the other side, PPI intake was a protective factor (P<0.05). The incidence of new-onset ACS was 1.44% (50/3 464) in PPI group, compared with 1.34% (76/5 654) in no PPI group (P>0.05). PPI use for the prevention of UGIB after PCI didn't increase the recurrence of ACS. CONCLUSIONS: The incidence of UGIB is 0.61% in ACS patients on dual antiplatelet therapy (aspirin and clopidogrel) for 1 year after PCI and falls year by year.Administration of PPI after PCI protects patients from UGIB, especially in those with precious history of peptic ulcer and renal impairment.

[Determination of in vitro synergy by a checkerboard method when 3 core antimicrobial agents of the retreatment new scheme combined against MDR-MTB and XDR-MTB].

OBJECTIVE: In order to detect the in vitro synergistic effect of 4 drugs-pasiniazid (PA), moxifloxacin, rifabutin and rifapentini on multidrug-resistant mycobacterium tuberculosis (MDR-MTB) and extensively drug-resistant mycobacterium tuberculosis(XDR-MTB), which were core drugs of"The program of retreatment research of tuberculosis". METHOD: The checkerboard method was used to detect the minimum inhibitory concentration (MIC) of antituberculosis drug combination schemes (moxifloxacin-PA, moxifloxacin-PA-rifabutin and moxifloxacin-PA-rifapentini) to 40 strains of clinical drug resistant MTB(20 strains of MDR-MTB and 20 XDR-MTB) and the standard strain H37Rv, by calculating the fractional inhibitory concentration index of joint action in vitro to judge the combined effect, with fractional inhibitory concentration index(FICI)≤0.5 and FICI≤0.75 as the basis of 2 drugs and 3 drugs showing synergy. RESULTS: The FICI of moxifloxacin-PA scheme for DR-MTB was 0.125 to 1.000, only 5 strains with a FICI ≤0.5, showing synergistic effect. The FICI of moxifloxacin-Pa-rifabutin scheme with 20 strains of MDR-MTB ranged from 0.310 to 1.260, 10 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifabutin scheme with 20 strains of XDR-MTB ranged from 0.215 to 1.250, 11 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifapentini scheme with 20 strains of MDR-MTB ranged from 0.150 to 0.780, 19 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifapentini scheme with 20 strains of XDR-MTB ranged from 0.200 to 1.280, 16 strains with a FICI≤0.75, showing synergistic effect. CONCLUSIONS: The synergistic effect of moxifloxacin-PA scheme was poor, but showing better synergy when further combined with rifabutin or rifapentini. Rifabutin showed better effect than rifapentini, but the synergistic effect of moxifloxacin-PA-rifabutin combination scheme was poor than that of moxifloxacin-PA-rifapentini combination scheme.

Molecular cloning and activity analysis of a seed-specific FAD2-1B gene promoter from Glycine max.

Microsomal omega-6 fatty acid desaturase (FAD2-1B) is an enzyme that regulates the polyunsaturated fatty acid content in soybeans (Glycine max). In this study, the FAD2-1B gene was determined to be highly expressed in soybean seeds using quantitative real-time PCR(qRT-PCR). To investigate the expression pattern and activity of the FAD2-1B promoter, a 1929 bp 5'-upstream genomic DNA fragment, named PF, was isolated according to the soybean genomic sequence. Sequence analysis revealed the presence of many motifs related to seed-specific promoters in the PF fragment, such as E-box, SEF4, Skn-1 motif, AACACA, AATAAA and so on. Tobacco transgenics carrying the gus reporter gene driven by the PF and/or 35S promoters were confirmed by PCR and RT-PCR. qRT-PCR and histochemical GUS assays showed that the PF promoter could regulate gus gene accumulation in seeds and the expression level was higher than in other organs. In the meantime, it exhibited similar activity to the 35S promoter in seeds, which could be associated with seed-related cis-elements found in the 1-248 bp, 451-932 bp, and 1627-1803 bp regions of the promoter.

Inflammation and oxidative stress are lower in physically fit and active adults.

The objective of this study was to determine if the inverse relationship between perceived physical fitness (pFIT) and exercise frequency (ExFreq) levels and chronic inflammation and oxidative stress exists after making statistical adjustments for confounders including body mass index (BMI), age, gender, and cigarette smoking. Study participants (60% female and 40% male; n = 998) varied widely in age (18-85 years) and BMI (16.7-52.7 kg/m(2)) completed an extensive medical/health and lifestyle questionnaire, and data were used to establish pFIT and ExFreq tertiles. Biomarkers included serum C-reactive protein (CRP), total blood leukocytes, five plasma cytokines [interleukin (IL)-6, IL-10, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP1), and granulocyte colony-stimulating factor (GCSF)], F2 -isoprostanes, ferric reducing ability of plasma (FRAP), and oxygen radical absorbance capacity (ORAC). A general linear model was used to examine relationships between pFIT and ExFreq with inflammation and oxidative stress while controlling for age, gender, BMI, and smoking. Benjamini-Hochberg method for false discovery rate correction was used for multiple testing corrections. Significant tests (P < 0.05) for trend were found for the effect of pFIT and ExFreq on CRP, white blood cell, IL-6, TNF-α, GCSF, and F2 -isoprostanes, but not MCP1, IL-10, FRAP, and ORAC, after adjustment for confounders. These data indicate that an inverse relationship exists among chronic inflammation, oxidative stress, and pFIT and ExFreq at the community level even after adjustment for important confounders.

First Report of Leaf Disease on Cinnamomum subavenium Caused by Colletotrichum fioriniae in China.

Cinnamomum subavenium Miq. (Lauraceae) is a subtropical arbor plant widely distributed in southwest China. It has a long history of cultivation and has been widely used in traditional Chinese medicine, food flavors, and industrial materials. In August 2010, a serious leaf disease was observed on wild Cinnamomum subavenium growing in Gutianshan Nature Reserve, Zhejiang, China. Lesions were approximately 1.0 cm in diameter and the margin of the lesions was light to dark brown and the middle was gray to pale yellowish. Necrotic lesions were surface disinfected with 1% sodium hypochlorite for 1 min and 70% ethanol for 3 min, and isolations were made from lesion edges onto potato dextrose agar (PDA). Three plants were tested and a fungus was consistently isolated from lesions. Colonies of this fungus on PDA were at first gray becoming pinkish gray with age, with salmon pink conidial masses, and the reverse of the colony was pink. The growth rate was 10.82 to 11.95 mm per day (average = 11.58 ± 0.25, n = 6) on PDA at 25°C. Conidia were oblong or cylindrical with acute ends, occasionally guttulate, hyaline, 7.5 to 14.5 × 2.5 to 4.3 µm (average = 11.25 ± 0.5 × 3.4 ± 0.4, n = 30). These characteristics matched the description of Colletotrichum fioriniae (Marcelino & Gouli) R.G. Shivas & Y.P. Tan (2). DNA was extracted from one isolate and the rDNA-internal transcribed spacer (ITS) region was amplified and sequenced using primers ITS1 and ITS4 (1). The ITS sequence of the isolate (GenBank Accession No. JN208890) shared 100% identity to the holotype of C. fioriniae (Accession No. EF464594). The pathogenicity of C. fioriniae on Cinnamomum subavenium was confirmed through inoculation. Three freshly harvested, healthy leaves were washed under running tap water, immersed in 5% sodium hypochlorite for 3 min and 70% ethanol for 1 min, rinsed three times in sterilized water, and finally dried with sterilized tissue paper. Plant leaves were inoculated with a concentration of 2.5 × 106 spores/ml. Sterilized water was used for controls. All the leaves inoculated with C. fioriniae were symptomatic with round to elliptical lesions with a brown margin 14 days postinoculation. The fungus, reisolated from symptomatic leaf tissue, had the same morphological and cultural characteristics of C. fioriniae. Although C. gloeosporioides has been reported from several species in the genus Cinnamomum ( http://nt.ars-grin.gov/fungaldatabases/ ), to our knowledge, this is the first report of leaf disease on Cinnamomum subavenium caused by a Colletotrichum species. References: (1) H. Prihastuti et al. Fungal Divers. 39:89, 2009. (2) R. G. Shivas and Y. P. Tan. Fungal Divers. 39:111, 2009.

Predicting survival and immune microenvironment in colorectal cancer: a STAT signaling-related signature.

BACKGROUND: Despite research advances, studies on predictive models of colorectal cancer (CRC) remain scarce and none have evaluated signal transducer and activator of transcription (STAT) signaling. AIM: To develop an effective prognostic signature for and evaluate its association with immune microenvironment. DESIGN: Comprehensive analysis based on The Cancer Genome Atlas and Gene Expression Omnibus databases with experimental validation. METHODS: Gene expression and clinical profiles of CRC patients were extracted from the databases. Differentially expressed genes with prognostic values were used to construct a signature. Immune cell infiltration and composition were further evaluated by TIMER, single-sample gene set enrichment and CIBERSORT analyses. The impact of the hub gene Caveolin-1 (CAV1) on cell proliferation, apoptosis, senescence and tumor angiogenesis was experimentally validated. RESULTS: The five-gene-based STAT signaling-related prognostic signature was significantly associated with CRC survival, and the nomogram was with improved prognostic efficacy than the conventional TNM stage. The STAT signaling-related signature was correlated with tumor immune microenvironment. CAV1 was further identified as the hub gene within the signature. CAV1 inhibits the proliferation and induces the apoptosis as well as senescence of CRC cells. In addition, the tumor angiogenesis of CRC can be suppressed by CAV1 overexpression. CONCLUSIONS: The STAT signaling-related signature effectively predicts the prognosis and regulates tumor immune microenvironment in CRC. Our study underscores the role of STAT regulator, CAV1, as an important tumor suppressor in CRC carcinogenesis. Modulating STAT and its regulators could be a promising strategy for CRC in clinical practice.

p50-NF-kappaB complexes partially compensate for the absence of RelB: severely increased pathology in p50(-/-)relB(-/-) double-knockout mice.

RelB-deficient mice (relB(-/-)) have a complex phenotype including multiorgan inflammation and hematopoietic abnormalities. To examine whether other NF-kappaB/Rel family members are required for the development of this phenotype or have a compensatory role, we have initiated a program to generate double-mutant mice that are deficient in more than one family member. Here we report the phenotypic changes in relB(-/-) mice that also lack the p50 subunit of NF-kappaB (p50(-/-)). The inflammatory phenotype of p50(-/-)relB(-/-) double-mutant mice was markedly increased in both severity and extent of organ involvement, leading to premature death within three to four weeks after birth. Double-knockout mice also had strongly increased myeloid hyperplasia and thymic atrophy. Moreover, B cell development was impaired and, in contrast to relB(-/-) single knockouts, B cells were absent from inflammatory infiltrates. Both p50(-/-) and heterozygous relB(-/+) animals are disease-free. In the absence of the p50, however, relB(-/+) mice (p50(-/-)relB(-/+)) had a mild inflammatory phenotype and moderate myeloid hyperplasia. Neither elevated mRNA levels of other family members, nor increased kappaB-binding activities of NF-kappaB/Rel complexes could be detected in single- or double-mutant mice compared to control animals. These results indicate that the lack of RelB is, in part, compensated by other p50-containing complexes and that the "classical" p50-RelA-NF-kappaB activity is not required for the development of the inflammatory phenotype.

B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-kappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogen-activated cells.

Rel and nuclear factor (NF)-kappaB1, two members of the Rel/NF-kappaB transcription factor family, are essential for mitogen-induced B cell proliferation. Using mice with inactivated Rel or NF-kappaB1 genes, we show that these transcription factors differentially regulate cell cycle progression and apoptosis in B lymphocytes. Consistent with an increased rate of mature B cell turnover in naive nfkb1-/- mice, the level of apoptosis in cultures of quiescent nfkb1-/-, but not c-rel-/-, B cells is higher. The failure of c-rel-/- or nfkb1-/- B cells to proliferate in response to particular mitogens coincides with a cell cycle block early in G1 and elevated cell death. Expression of a bcl-2 transgene prevents apoptosis in resting and activated c-rel-/- and nfkb1-/- B cells, but does not overcome the block in cell cycle progression, suggesting that the impaired proliferation is not simply a consequence of apoptosis and that Rel/NF-kappaB proteins regulate cell survival and cell cycle control through independent mechanisms. In contrast to certain B lymphoma cell lines in which mitogen-induced cell death can result from Rel/NF-kappaB-dependent downregulation of c-myc, expression of c-myc is normal in resting and stimulated c-rel-/- B cells, indicating that target gene(s) regulated by Rel that are important for preventing apoptosis may differ in normal and immortalized B cells. Collectively, these results are the first to demonstrate that in normal B cells, NF-kappaB1 regulates survival of cells in G0, whereas mitogenic activation induced by distinct stimuli requires different Rel/NF-kappaB factors to control cell cycle progression and prevent apoptosis.

Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis in China.

BACKGROUND: Multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) continues to be a challenge in China. Bedaquiline (BDQ) is associated with accelerated sputum culture conversion and favourable treatment outcomes when added to a preferred background regimen. This post-hoc study aimed to assess the outcomes of BDQ treatment in Chinese patients with MDR/XDR-TB.METHODS: Data from 51 Chinese patients who participated in a global Phase 2, open-label, single-arm study (TMC207-C209) were analysed for effectiveness and safety of the BDQ-containing regimen.RESULTS: During the 24-week BDQ treatment, adverse events (AEs) occurred in 48 patients (94.1%), with the most common AE being hyperuricemia. Drug-induced liver injury (DILI) was reported in 13 patients (25.5%); serious DILI was reported in one patient (2.0%). Seven (13.7%) AEs were considered to be possibly related to BDQ by the investigators. Only one Grade 1 QTc prolongation was reported; no QTcF >500 ms was reported. One death occurred after BDQ treatment due to progressive TB. The median time to sputum culture conversion was 85 days based on the 24-week data. The sputum culture conversion rate was 82% at 24 weeks and 78% at 120 weeks; 66% of patients achieved a cure.CONCLUSIONS: BDQ was well-tolerated and effective for treating MDR-TB among Chinese patients.

T-cell receptor beta-chain expression: dependence on relatively few variable region genes.

Fifteen independently isolated complementary DNA clones that contain T-cell receptor (TCR) V beta genes were sequenced and found to represent 11 different V beta genes. When compared with known sequences, 14 different V beta genes could be defined from a total of 25 complementary DNA's; 11 clones therefore involved repeated usage of previously identified V beta's. Based on these data, we calculate a maximum likelihood estimate of the number of expressed germline V beta genes to be 18 with an upper 95 percent confidence bound of 30 genes. Southern blot analysis has shown that most of these genes belong to single element subfamilies which show very limited interstrain polymorphism. The TCR beta-chain diversity appears to be generated from a limited V beta gene pool primarily by extensive variability at the variable-diversity-joining (V-D-J) junctional site, with no evidence for the involvement of somatic hypermutation.

Requirement of tissue-selective TBP-associated factor TAFII105 in ovarian development.

Transcription factor TFIID, composed of TBP and TAFII subunits, is a central component of the RNA polymerase II machinery. Here, we report that the tissue-selective TAFII105 subunit of TFIID is essential for proper development and function of the mouse ovary. Female mice lacking TAFII105 are viable but infertile because of a defect in folliculogenesis correlating with restricted expression of TAFII105 in the granulosa cells of the ovarian follicle. Gene expression profiling has uncovered a defective inhibin-activin signaling pathway in TAFII105-deficient ovaries. Together, these studies suggest that TAFII105 mediates the transcription of a subset of genes required for proper folliculogenesis in the ovary and establishes TAFII105 as a cell type-specific component of the mammalian transcriptional machinery.

MiR-219-5p promotes spinal cord injury recovery by inhibiting NEUROD2-regulated inflammation and oxidative stress.

OBJECTIVE: The aim of this study was to explore the specific role of miR-219-5p in spinal cord injury (SCI), and to investigate its underlying mechanism. MATERIALS AND METHODS: The SCI model was first constructed in mice, and the motor function of each mouse was evaluated by the Basso Beattie Bresnahan (BBB) method. The protein and mRNA expression levels of miR-219-5p and NEUROD2 in SCI mice were detected by Western blot and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. Subsequently, all mice were assigned into 3 groups, including the sham operation group, the SCI group and the SCI+miR-219-5p group. The levels of inflammatory factors (TNF-α, IL-1ß and IL-6) were detected by Western blot and qRT-PCR. Meanwhile, reactive oxygen species (ROS) were detected by flow cytometry. Target genes of miR-219-5p were predicted by TargetScan and verified by Luciferase reporter gene assay. For in vitro experiments, the possible molecule mechanism of miR-219-5p in regulating NEUROD2 was detected by Western blot. RESULTS: MiR-219-5p was significantly downregulated after SCI. The expression level of miR-219-5p was decreased in the SCI group than that of the sham operation group in a time-dependent manner, which reached the lowest level on the 7th day. Besides, the mRNA and protein levels of NEUROD2 in the SCI group were both remarkably increased in a time-dependent manner, which reached a peak on the 7th day. The levels of inflammatory factors (TNF-α, IL-1ß and IL-6) and ROS were significantly higher in the SCI group, which could be reversed by miR-219-5p mimics transfection in SCI mice. Meanwhile, the BBB score in the SCI group was remarkably lower than that of the SCI + miR-219-5p group from the 4th day after SCI. TargetScan predicted that NEUROD2 was the target gene of miRNA-219-5p. In addition, Western blot results indicated that miR-219-5p could regulate NEUROD2, eventually promoting the recovery of SCI. CONCLUSIONS: Overexpressed miR-219-5p promotes SCI recovery and motor function elevation via alleviating NEUROD2-regulated inflammation and oxidative stress.