Current Issue

2017 Vol.2 No.3 Published:31 August 2017

Special Topics on the Basis and Diagnosis and Treatment of Tuberculosis

Host-direct therapy for tuberculosis:opportunity and challenges CHEN Xin-chun, WEN Zhi-hua 2017, 2 (3):  129-132.  Abstract ( 143)    PDF (1042KB) ( 613 )    Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is still one of the major causes of mortality worldwide. Despite the availability of effective antibiotics for tuberculosis (TB), 3%~9% patients relapse after receiving DOTS treatment. Furthermore, the spread of drug-resistant TB (DR-TB), expecially multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) makes it more difficult to cure. Novel drugs/strateges are urgently needed to arrest global transmission and prevent the uncontrolled development of MDR-TB. Unlike antibiotics and chemotherapy drugs, which directly kill Mtb, Host-directed therapy (HDT) enhances the host response against MTB infection to reduce excess inflammation, prevent tissue damage, repair damaged tissues and enhance the effectiveness of TB drug therapy. Therefore, HDT offers one potential solution to cure MDR-TB and improve the efficacy of anti-TB treatment.

Immunogenicity and protective efficacy of mycobacterium tuberculosis antigen PE31 WANG Yu-chen, CHEN Fu-zeng, HUANG Ying-rui, ZHANG Lu, LIU Jun 2017, 2 (3):  155-159.  Abstract ( 240)    PDF (1128KB) ( 578 )    Objective The purpose of this study is to examine the immunogenicity and protective efficacy of PE31, which is a PE-PPE family protein that is under the control of the PhoPR two-component system and Lsr2 global regulator, against Mycobacterium tuberculosis(MTB); and to evaluate its potential in subunit vaccine development. Methods The sequence of PE31 was analyzed for potential CD4+ and CD8+T cell epitopes. PE31 and Ag85A were cloned into pET-28a and recombinant proteins were expressed in and purified from E. coli. C57BL/6 mice were immunized with purified antigens formulated in adjuvant and the production of antigen-specific Th1 cytokines and antibody were determined. PE31 and Ag85A were also cloned into pcDNA3.1(+) for mammalian cell expression. The resulting DNA vaccines were used to immunize BALB/c mice subcutaneously. The mice were then challenged intravenously by MTB H37Rv. Bacterial burdens in the lungs and spleen were determined 4 weeks post-infection. Results There are similar numbers of predicted CD4+ and CD8+T cell epitopes in PE31 and Ag85A. Immunization experiments showed that PE31 induced higher level of IFN-γ and TNF-α (~600 pg/ml) than Ag85A and similar levels of antibody response. Mice immunized with the DNA vaccine expressing PE31 had 0.3-0.4log10 fewer MTB counts in the lungs and spleen than those immunized with the empty vector. Conclusions It is demonstrated that PE31 is highly immunogenic and protective, and is an attractive candidate for the development of novel subunit vaccines.

Resistance analysis of extensively drug-resistant mycobacterium tuberculosis isolatesagainst linezolid ZONG Zhao-jing, JING Wei, HUO Feng-min, SHANG Yuan-yuan, LIANG Qian, LI Yun-xu, PANG Yu, HUANG Hai-rong 2017, 2 (3):  160-163.  Abstract ( 177)    PDF (865KB) ( 737 )    Objective To investigate the resistant characteristic of extensively drug-resistant Mycobacterium tuberculosis isolatesagainst linezolid (Lzd). Methods Ninety extensively drug-resistant Mycobacterium tuberculosis clinical isolates were collected from Beijing Chest Hospital during 2012-2014. Broth dilution micro-plate alamar blue assay (MABA) was used to detect the minimal inhibitory concentration(MIC) of isolates against Lzd. Lnz resistant genes rplC、rplDand 23S rRNA were sequenced for all the enrolled isolates. Results Total of ninety isolates were enrolled .The resistant rate to common second-line anti-tuberculosis drugs is high while only 5(5/90, 5.6%) of these isolates resistant to Lzd. Mutations at 154 locus of rplC were detected in two of the isolates, and Cys→Arg has no obvious accounting to Lzd resistance. All the strains had no mutations in rplD and 23S rRNA. Conclusion The study demonstrated that linezolid resistance and mutation were rarely among extensively drug-resistant Mycobacterium tuberculosisisolates. This drug is of great use in therapy of extensively drug-resistant tuberculosis.

Efficacy of bronchoscopy-based comprehensive interventional therapy of bronchial tuberculosis YE Tao-sheng, ZHANG Jiao-hong, TANG Yi-min, ZHANG Pei-ze, DENG Guo-fang 2017, 2 (3):  164-166.  Abstract ( 198)    PDF (1395KB) ( 706 )    Objective To evaluate the efficacy of comprehensive Interventional therapy by bronchoscopy in the treatment of endobronchial tuberculosis(EBTB). Methods Two hundreds and thirty five patients with endobronchial tuberculosis were treated with bronchoscopy based comprehensive interventional therapy. These patients had no severe bronchostenosis and bronchomalacia. They were treated with localized frozen\microwave\clipping\balloon dilator\local medicine injection through bronchoscopy and received anti-tuberculosis treatment and aerosol inhalation. Clinical symptoms, bronchoscopy findings and CT imaging findings were compared to evaluate the efficacy. Results All the 235 patients underwent an average of 6 comprehensive treatments in the duration of six weeks. All patients benefited from the treatment as the clinical symptoms improved obviously. Most of the patients (194/235) had the lesion in trachea and bronchial disappeared, as well as the lung lesions absorbed. No obvious adverse reactions were observed during the comprehensive treatment. No bronchostenosis and EBTB relapse were observed in the 48 weeks’ follow-up. Conclusion The bronchoscopy-based comprehensive interventional therapy is effective and safe for treatment of endobronchial tuberculosis.

Original Articles

Application values of antigen specific-IFN-γresponses in tuberculosis pelvic inflammation patients using Elispot LIU Yu-juan, CAI Qiu-e, DUAN Yan-hui, ZHANG Ming-xia, YANG Qian-ting DENG Qun-yi 2017, 2 (3):  167-169.  Abstract ( 173)    PDF (1161KB) ( 698 )    Objective To investigate mycobacterium tuberculosis antigen specific IFN-γ response in tuberculosis pelvic inflammation patients（TPIP）by Elispot. Methods The levels of IFN-γ production in response to mycobacterium tuberculosis antigens in TPIP (n=63) and non-TPIP(n=19) were evaluated by an in-house Elispot. Result By using Elispot, the level of IFN-γin TPIP was much higher than the non-TPIP ,and there was statistical difference between the TPIP and the non-TPIP(p<0.05).The positive rate in Elispot observed in TPIP and non-TPIP was 80.9%,10.5% respectively. Conclusion It is practical to differentiate the tuberculosis pelvic inflammation patients from the non tuberculosis pelvic inflammation patients by measuring the Mtb. antigen-specific IFN-γ response in the peripheral blood using our in-house Elispot assay. It is reliable to use it to diagnosis the TPIP.

Clinical analysis on 23 cases of pleural and pulmonary diseases complicated with ankylosing spondylitis ZHANG Ai-ping, HUANG Ke-feng, HE Zhi-jian, LIANG Xun-si, WEI Yun-hui, LU Wen-ren, WEI Ming, LIAO Yong 2017, 2 (3):  170-171.  Abstract ( 483)    PDF (851KB) ( 627 )    Objective To investigate the clinical features and surgery efficiency of patients suffering from pleural and pulmonary diseases complicated with Ankylosing Spondylitis(AS). Methods The clinical data of 23 patients suffering from pleural and pulmonary diseases (pulmonary tuberculosis cavities, pulmonary damages caused by tuberculosis, tuberculosis bronchiectasis, chronic tuberculosis empyema, pulmonary cyst, tuberculosis complicated with pneumothorax) complicated with AS, who were admitted in authored in author complicated with AS, who were admitted June 2015 to receive surgeries, were retrospectively analyzed. Results Different degrees of pulmonary restrictive ventilation dysfunction occurred in these patients. The surgeries were performed in 22 patients, including 16 cases of pulmonary lobectomy, 2 cases of pulmonary segment resection, 3 cases of empyema debridement added decortication (1 of which added pulmonary wedge resection), 1 case of pneumothorax repair added pleural friction fixation, and 1 case of being unable to perform the lung resection surgery due to that the incision could not open after thoracotomy. Complications occurred in 8 patients, including 5 cases of pulmonary infection, 4 cases of atelectasis, 4 cases of respiratory failure, 3 cases of heart failure, 1 case of bronchopleural fistula, and 1 case of incision infection. Among the cases of atelectasis repeatedly received aspiration of sputum by bronchoscope, there was 1 case of being unable to coughing up phlegm, who received aspiration of sputum 12 times repeatedly. For the subsequent 23 cases followed up, no death occurred, while 22 cases were cured and 1 case showed that pulmonary aspergilloma occurred in right upper residual cavity at 7 months after the operation and repeated mild hemoptysis, which was then treated by bronchial artery embolization. Conclusion Pulmonary restrictive ventilation dysfunction mostly occurred in patients suffering from pleural and pulmonary diseases complicated with AS. The surgery is difficult, and postoperative complications are easily occurred. The surgery results are good mainly in pneumonia and atelectasis, but the management of respiratory tract is needed to be strengthened subsequently.

Cause analysis for delayed diagnosis of joint tuberculosis MA Ke, LIU Jin-zhu, LIU Jing, ZHOU Zhen-zhong 2017, 2 (3):  172-174.  Abstract ( 210)    PDF (856KB) ( 706 )    Objective To explore the clinical characteristic of joint tuberculosis patients in order to improve the diagnosis of the joint tuberculosis. Methods The clinical data of 109 joint tuberculosis patients admitted to Shenzhen the third people's hospital of orthopedics for treatment were collected and retrospectively analyzed. Results The joint tuberculosis frequently urred in young and middle aged adults in this group (85.32%, 93/109)); 55 cases (50.46%, 55/109)were secondary to tuberculosis; the lesions were found mainly in knee 41.28%（45/109）cases, ankle14.68%(16/109) cases and hip 12.84%（14/109）cases . The major clinical manifestations were local pain and limited activity. The initial misdiagnosis rate of joint tuberculosis patients was 74.31%(81/109). The joint tuberculosis was confirmed relying on the symptoms and signs, laboratory tests, imaging examination, other involvement of tuberculosis, abscess puncture, laboratory examination, surgical biopsy and efficiency of diagnostic anti-tuberculosis treatment. Finally, 16 cases were cured by anti-tuberculosis drugs and 66 cases were cured by surgery, with the cure rate of 100%. Conclusion Non-obvious early clinical manifestation, nondeterminacy of laboratory examination, limitation of imaging examination are the main reasons of misdiagnosis for joint tuberculosis. Comprehensive utilization of various tuberculosis specialized examination and the diagnostic anti-tuberculosis treatment are still the basic method for the diagnosis and treatment of joint tuberculosis.

Diagnostic value of CT in IgG4-related sialadenitis ZHANG Ao-dan, BIAN Jie, LUO Jia-wen, SUN Wei-hang 2017, 2 (3):  175-178.  Abstract ( 140)    PDF (1289KB) ( 791 )    Objective To investigate the characteristic CT images of IgG4-related sialadenitis. Methods The clinical and imaging data of 10 patients with IgG4- related sialadenitis confirmed by pathologic examination were retrospectively analyzed. In the 10 cases, 8 patients were performed with enhanced scan, and the imaging features such as lesion size, morphology, distribution, CT value and enhancement pattern were analyzed. Results All patients showed salivary gland diffuse or multi nodulated enlargement, including 4 cases of unilateral parotid involvement, 5 cases of unilateral submandibular gland involvement, 1 case of bilateral submandibular gland simultaneously, while 5 cases showed with submandibular lymph nodes increased, and 3 cases showed with cystic changes. CT scan showed lacking structured morphology of unilateral or bilateral salivary gland, presenting in multiple nodular, lightly lobulated or diffuse enlarged. Uneven enhancement was observed in the salivary glands during the arterial phase. And nodules were significantly enhanced, the unequal thickness low-density zone was formed between nodules, and little proliferation can be detected in the surrounding accompanying with increased small lymph nodes. Conclusion IgG4-related sialadenitis has specific characteristic CT features. Accurate knowledge of these signs facilitates to improve the preoperative diagnosis rate of IgG4-related sialadenitis.

The role of HMGB1 in inflammatory response and vulnerable plaque in coronary heart disease HU Ya-nan, DU Shao-hui, CHEN Si-nuo, HU Tian-xiang 2017, 2 (3):  179-182.  Abstract ( 460)    PDF (865KB) ( 784 )    Objective To study the relationship between the levels of HMGB1, MMP-9, and the stability of coronary artery atheromatous plaque, to further discover the relationship among immune response, inflammatory reaction and coronary heart disease.Method Fifty-eight coronary heart disease patients who were cured between - August 2013 to January 2014 in Guangdong Province Hospital Of Traditional Chinese Medicine were enrolled. Thirty healthy individuals who were cured during the same time in our hospital without structural heart disease (but with normal heart function) were enrolled as control group. ELISA kit was used to detect the HMGB1, MMP-9, concentration of stored examples.Result i) Serum HMGB1 level was gradually increased in the control groups, considering the SA, UA and AMI groups, and it indicated a significant statistic difference(P<0.05); and is higher than the controls. ii) Serum level of MMP-9 was significantly higher in coronary heart disease groups than the control group, and it indicated a significant statistic difference(P<0.05). iii) Serum levels of HMGB1、MMP-9 were also significantly different, HMGB1 and MMP-9 levels correlated positively (r=0.463 P<0.05).Conclusion HMGB1 has certain correlation with clinical routine detection of inflammation, blood lipid and other indicators, it could be inferred that HMGB1 was an independent factor of CHD classification, and could indirectly reflect the degree of active inflammation in plaque. HMGB1 was also positively correlated with MMP-9, suggesting that the detection of HMGB1 could predict plaque stability to a certain extent and provide a reliable basis for the anti-inflammatory treatment of coronary heart disease.