[Etiological analysis of a patient with multiple primary malignant neoplasms].

To investigate the etiology of multiple primary malignant neoplasms occurred in one patient. Retrospective analysis was performed on a 52-year-old female patient who was admitted to the Department of Endocrinology, the First Affiliated Hospital of Sun Yat-Sen University on October 7, 2021, due to "thyroid occupying lesion for one week". A complete systemic positron emission tomography examination of the patient indicated that the metabolic characteristics of the left thyroid nodules were consistent with medullary thyroid carcinoma, those of the right thyroid nodules were consistent with papillary thyroid carcinoma, and the metabolic characteristics of the T6-7 level were consistent with meningioma, and teratoma was found in the right ovarian region. Intradural subdural mass resection was performed on October 20, 2021, and bilateral total thyroidectomy, isthmus thyroidectomy, bilateral central lymph node dissection and left cervical lymph node dissection were performed on November 2, 2021. The postoperative pathologic diagnosises were meningioma (WHO Grade 1), medullary thyroid carcinoma (left side), and papillary thyroid carcinoma (right side).Whole exon gene sequencing revealed the presence of mutations in the ACAN and FLNB genes, which are associated with dysplasia, as well as mutations in the DDX41 and JAK2 genes, which are linked to active pro-proliferation signaling and tumor susceptibility. In this study, a gene mutation pattern which could lead to multiple primary malignant neoplasms was found.

[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.

[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.

Role of bicyclol in preventing drug-induced liver injury in tuberculosis patients with liver disease.

SETTING: Four hospitals in China. OBJECTIVE: To evaluate the clinical efficacy and safety of using bicyclol in conjunction with glucurolactone in preventing drug-induced liver injury (DILI) in tuberculosis (TB) patients suffering from underlying liver disease. DESIGN: A total of 240 initially treated TB patients who were healthy hepatitis B carriers or had pure steatosis were randomised into two equal groups; both received an oral glucurolactone tablet 600 mg/day (200 mg three times daily) as basic liver protection. The test group also received 75 mg/day (25 mg three times daily) bicyclol tablets orally, while the control group received no other liver protection. The incidence of liver injury in the two groups, the adjustment or termination of anti-tuberculosis chemotherapy and any adverse reactions were assessed. RESULTS: The incidence rate and level of severity of liver injury and the termination rate of anti-tuberculosis treatment in the test group were lower than that of the control group (P < 0.05). The overall time of occurrence of liver injury was significantly different between the two groups (P < 0.05). CONCLUSION: Adding bicyclol to basic liver protectants may effectively and safely prevent the occurrence of anti-tuberculosis DILI in patients with underlying liver disease, and help simplify anti-tuberculosis treatment.

Glucose regulates secretion of exogenously expressed insulin from HepG2 cells in vitro and in a mouse model of diabetes mellitus in vivo.

Glucose-controlled insulin secretion is a key component of its regulation. Here, we examined whether liver cell secretion of insulin derived from an engineered construct can be regulated by glucose. Adenovirus constructs were designed to express proinsulin or mature insulin containing the conditional binding domain (CBD). This motif binds GRP78 (HSPA5), an endoplasmic reticulum (ER) protein that enables the chimeric hormone to enter into and stay within the ER until glucose regulates its release from the organelle. Infected HepG2 cells expressed proinsulin mRNA and the protein containing the CBD. Immunocytochemistry studies suggested that GRP78 and proinsulin appeared together in the ER of the cell. The amount of hormone released from infected cells varied directly with the ambient concentration of glucose in the media. Glucose-regulated release of the hormone from infected cells was rapid and sustained. Removal of glucose from the cells decreased release of the hormone. In streptozotocin-induced diabetic mice, when infected with adenovirus expressing mature insulin, glucose levels declined. Our data show that glucose regulates release of exogenously expressed insulin from the ER of liver cells. This approach may be useful in devising new ways to treat diabetes mellitus.

Linezolid in the treatment of MDR-TB: a retrospective clinical study.

BACKGROUND: There is limited information on Chinese patients with multidrug-resistant tuberculosis (MDR-TB) treated with a linezolid-containing regimen. OBJECTIVE: To examine treatment outcomes among MDR-TB patients who were treated with linezolid at the Shanghai Pulmonary Hospital, China. DESIGN: We retrospectively reviewed 151 patients who were treated for MDR-TB from 2007 to 2010. RESULTS: Eighteen MDR-TB patients, including 15 with extensively drug-resistant TB, received linezolid as part of their individualised treatment regimens. Patients had isolates resistant to a median of 7 drugs (range 5-11). Of the 18 cases, 17 had cavitary changes and positive sputum smear microscopy results at the time of MDR-TB diagnosis. Culture conversion occurred in all cases at a median of 7 weeks. At data censure, 9 of the 18 patients had achieved treatment success. Three continued to receive treatment. There were no deaths. Six patients had a poor outcome, including 1 default, 2 treatment failures and 3 relapses. Side effects occurred in 17 patients, including myelosuppression, neurotoxicity and gastrointestinal adverse events. Adverse events were managed by combinations of temporary suspension of linezolid in 1 patient, dose adjustment in 17 patients and symptom management in 13 patients. CONCLUSIONS: Linezolid may have efficacy in the treatment of MDR-TB, although treatment was complicated by adverse events.

Clofazimine in the treatment of multidrug-resistant tuberculosis.

Clofazimine has shown activity against Mycobacterium tuberculosis, including multidrug-resistant strains in vitro and in animal studies. However, clinical experience with clofazimine in multidrug-resistant tuberculosis (MDR-TB) is scarce. We reported our clinical experience with 39 MDR-TB patients treated with combination regimens that included clofazimine. From January 2008 to March 2011, 39 patients received clofazimine for the treatment of MDR-TB in Shanghai Pulmonary Hospital. Patients had isolates resistant to a median of six drugs (range, 2-11 drugs). Of the 39 cases, 36 had cavitary changes noted on initial chest radiograph or chest computed tomography, and positive sputum-smear microscopy results at the time of MDR-TB diagnosis. At data censure, 15 of the 39 patients had successful therapy, with at least five consistently negative cultures documented for the final 12 months of treatment. Eleven continued to receive treatment. There were no deaths. Thirteen patients had a poor outcome, including four defaults and nine treatment failures. Culture conversion occurred in 22 cases at a median of 12 weeks. Side-effects occurred in 34 patients, mainly including skin discolouration, ichthyosis and gastrointestinal adverse events. No patients reported significant toxicity likely to be attributable to clofazimine therapy. Adverse events were managed by combinations of dose adjustment and symptom management. In our experience, clofazimine was well tolerated and may have efficacy in the treatment of MDR-TB.

Significant increase in natural-killer T cells in patients with tuberculosis complicated by type 2 diabetes mellitus.

This study examined the frequency of Vα24(+)/Vß11(+) natural-killer T (NKT) cells from peripheral blood and bronchoalveolar lavage fluid in pulmonary tuberculosis (TB) patients with or without diabetes mellitus (DM). The clinical grade of TB was significantly higher among diabetic patients. NKT cells from both peripheral blood and bronchoalveolar lavage were significantly increased in diabetic TB patients compared with non-diabetic TB patients. This may be due to the generally higher bacillary burden in diabetic TB patients. NKT cells from peripheral blood mononuclear cells in TB patients with or without DM were significantly increased, compared with levels in non-TB diabetic patients and healthy controls. The measurement of NKT cells from peripheral blood has the potential to be a reliable, non-invasive, practical diagnostic marker for active TB.

Diagnostic value of adenosine deaminase in cerebrospinal fluid for tuberculous meningitis: a meta-analysis.

OBJECTIVE: To determine the accuracy of adenosine deaminase (ADA) measurements in the diagnosis of tuberculous meningitis (TBM). DESIGN: After a systematic review of English language studies, the sensitivity, specificity and accuracy of ADA concentrations in the diagnosis of cerebrospinal fluid (CSF) were evaluated using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance. RESULTS: Ten studies met our inclusion criteria. The sensitivity of ADA in the diagnosis of TBM was 0.79 (95%CI 0.75-0.83), specificity 0.91 (95%CI 0.89-0.93), positive likelihood ratio 6.85 (95%CI 4.11-11.41), negative likelihood ratio 0.29 (95%CI 0.19-0.44) and diagnostic odds ratio 26.93 (95%CI 12.73-56.97). CONCLUSION: Our data suggest that ADA in the CSF can be a sensitive and specific target and a critical criteria for the diagnosis of TBM.

Induced recovery of defective membrane expression of a CC chemokine receptor 5 mutant by phytohemagglutinin.

CC chemokine receptor 5 (CCR5) is a member of the G-protein-coupled receptor superfamily. It plays an important role in macrophage tropic human immunodeficiency virus-1 entry and in some inflammatory reactions. CCR5-893(-) is a single-nucleotide deletion that results in complete truncation of the C tail of the gene product. We detected CCR5-893(-) in a sample of patients infected with non-tuberculosis mycobacteria and found that it was maintained heterozygously with a frequency of 2%. There is no association between this mutation and any immunodeficiency. Membrane expression of CCR5-893(-) was substantially reduced compared to the wild type, but this defective surface presentation recovered greatly recovered in the presence of 2 mg l(-1) phytohemagglutinin (PHA). However, PHA inducement did not affect the total intracellular expression of CCR5-893(-) or wild-type CCR5. Thus we suggest there exist some PHA-induced factor(s) that could mediate the presentation of truncated CCR5.

Occupation and lung cancer risk among women in northern China.

Lifetime occupational histories were obtained in a case-control study of 965 female lung cancer patients and 959 controls selected from the general population in Shenyang and Harbin, People's Republic of China, where most women have worked outside the home. After adjusting for smoking, we found a significantly increased risk of lung cancer associated with employment involving the manufacture of transportation equipment (OR = 1.6, 95% CI = 1.0, 2.6), in particular the manufacturing of automobiles (OR = 3.0, 95% CI = 1.4, 6.4). Metal smelting and treatment workers were at an increased risk of lung cancer (OR = 1.5, 95% CI = 1.0, 2.1); the highest risks were observed among metal surfacers (OR = 3.1, 95% CI = 1.1, 9.0) and currently employed foundry workers (OR = 13.0, 95% CI = 1.7, 99.4). On the other hand, about a 50% decreased risk of lung cancer was observed among those employed in textile industries or as leaders of state and party organizations. Based on self-reports, exposures to coal dust and smoke from burning fuel at the workplace were also significant risk factors. The findings were similar when the analyses were confined to nonsmokers and were comparable across the major cell types of lung cancer.

Lung cancer among women in north-east China.

A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. Although the amount smoked was low (the cases averaged eight cigarettes per day), the percentage of smokers among women over age 50 in these cities was nearly double the national average. Air pollution from coal burning stoves was implicated, as risks of lung cancer increased in proportion to years of exposure to 'Kang' and other heating devices indigenous to the region. In addition, the number of meals cooked by deep frying and the frequency of smokiness during cooking were associated with risk of lung cancer. More cases than controls reported workplace exposures to coal dust and to smoke from burning fuel. Elevated risks were observed for smelter workers and decreased risks for textile workers. Prior chronic bronchitis/emphysema, pneumonia, and recent tuberculosis contributed significantly to lung cancer risk, as did a history of tuberculosis and lung cancer in family members. Higher intake of carotene-rich vegetables was not protective against lung cancer in this population. The findings were qualitatively similar across the major cell types of lung cancer, except that the associations with smoking and previous lung diseases were stronger for squamous/oat cell cancers than for adenocarcinoma of the lung.

Smoking, air pollution, and the high rates of lung cancer in Shenyang, China.

A case-control study involving interviews with 1,249 patients with lung cancer and 1,345 population-based controls was conducted in Shenyang, an industrial city in northeastern China, where mortality rates are high among men and women. Cigarette smoking was found to be the principal cause of lung cancer in this population, accounting for 55% of the lung cancers in males and 37% in females. The attributable risk percentage among females is high compared to elsewhere in China, largely because of a higher prevalence of smoking among women. After adjustment for smoking, there were also significant increases in lung cancer risk associated with several measures of exposure to air pollutants. Risks were twice as high among those who reported smoky outdoor environments, and increased in proportion to years of sleeping on beds heated by coal-burning stoves (kang), and to an overall index of indoor air pollution. Threefold increases in lung cancer risk were found among men who worked in the nonferrous smelting industry, where heavy exposures to inorganic arsenic have been reported. The associations with both smoking and indoor air pollution were stronger for squamous cell and small cell carcinomas than for adenocarcinoma of the lung. Risks due to smoking or air pollution were not greatly altered by adjustment for consumption of fresh vegetables or sources of beta carotene or retinol, prior chronic lung diseases, or education level. The findings suggest that smoking and environmental pollution combine to account for the elevated rates of lung cancer mortality in Shenyang.

Air pollution and lung cancer in Liaoning Province, People's Republic of China.

A correlation study linking age-adjusted lung cancer mortality rates with indices of air pollution was conducted as a first step in the investigation of the high rate of lung cancer in Liaoning Province. Mortality rates for this cancer during 1976-78 for males and females were elevated in the large industrial cities with metallurgical processing and machinery manufacturing industries, after smoking was taken into account. However, there was little correlation between measures of total suspended particulates and lung cancer rates across the 10 major cities of the Province. Neighborhood air pollution indices correlated significantly with local commune mortality rates within the largest city, and lung cancer rates were higher near certain point sources of industrial pollution (including a copper-zinc smelter). These findings indicate that the atmospheric pollution in this northern Chinese province may contribute to lung cancer risk and that further analytic epidemiologic study in this high-risk area is warranted for evaluation of the role of outdoor and indoor air pollutants.