Prediction of different interventions on the burden of drug-resistant tuberculosis in China: a dynamic modelling study.

BACKGROUND: Tuberculosis (TB) is one of the top 10 causes of death worldwide. The World Health Organization adopted the 'End TB Strategy' to end the global TB epidemic by 2035. However, achieving this goal will be difficult using current measures. METHODS: A Susceptible-Exposed-Infectious-Recovered (SEIR) model that distinguishes drug-sensitive (DS) and drug-resistant (DR) TB in the entire Chinese population was established. Goodness-of-fit tests and sensitivity analyses were used to assess model performance. Predictive analysis was performed to assess the effect of different prevention and control strategies on DR-TB. RESULTS: We used parameter fitting to determine the basic reproduction number of the model as R0 = 0.6993. The predictive analysis led to two major projections that can achieve the goal by 2035. First, if the progression rate of latently infected people reaches 10%, then there will be 92.2% fewer cases than in 2015. Second, if the cure rate of DR-TB increases to 40%, then there will be 91.5% fewer cases than in 2015. A combination of five interventions could lead to earlier achievement of the 2035 target. CONCLUSION: We found that reducing the probability of transmission and the rate of disease progression in patients with DR-TB and improving treatment compliance and the cure rate of patients with DR-TB can contribute to attaining the goal of the End TB Strategy.

Access to quality diagnosis and rational treatment for tuberculosis: real-world evidence from China-Gates Tuberculosis Control Project Phase III.

BACKGROUND: China has successfully reduced tuberculosis (TB) incidence rate over the past three decades, however, challenges remain in improving the quality of TB diagnosis and treatment. In this paper, we assess the effects of the implementation of "China National Health Commission (NHC) and Gates Foundation TB Prevention and Control Project" on the quality of TB care in the three provinces. METHODS: We conducted the baseline study in 2016 and the final evaluations in 2019 in the 12 selected project counties. We obtained TB patients' information from the TB Information Management System and reviewed medical records of TB cases in the TB designated hospitals. We compared TB diagnosis and treatment services with the national practice guideline and used Student's t-test and Pearson χ2 tests or Fisher's exact tests to compare the difference before and after the project implementation. RESULTS: The percentage of sputum smear-negative (SS-) patients taking culture or rapid molecular test (RMT) doubled between 2015 and 2018 (from 35% to 87%), and the percentage of bacteriologically confirmed pulmonary TB cases increased from 36% to 52%. RMT has been widely used and contributed an additional 20% of bacteriologically confirmed TB cases in 2018. The percentage of TB patients taking drug susceptibility tests (DST) also doubled (from 40% in 2015 to 82% in 2018), and the proportion of TB patients receiving adequate diagnosis services increased from 85% to 96%. Among all SS- TB patients, over 86% received the recommended diagnostic services at the end of the study period, an improvement from 75% prior to the project implementation. However, the proportion of TB patients treated irrationally using second-line anti-TB drugs (SLDs) increased from 12.6% in 2015 to 19.9% in 2018. The regional disparities remained within the project provinces, albeit the gaps between them narrowed down for almost all indicators. CONCLUSIONS: The quality of TB diagnosis services has been improved substantially, which is attributable to the coverage of new diagnosis technology. However, irrational use of SLDs remains a concern after the project implementation.

Impacts of a comprehensive tuberculosis control model on the quality of clinical services and the financial burden of treatment for patients with drug-resistant tuberculosis in China: a mixed-methods evaluation.

BACKGROUND: The China National Health Commission-Gates TB Project Phase III implemented a comprehensive TB control model including multiple interventions to address the burden of drug-resistant TB (DRTB). This study aims to evaluate the quality of DRTB clinical services and assess the financial burden of DRTB patients during the intervention period. METHODS: A mixed-methods approach was used to evaluate the effectiveness of interventions in the three project provinces: Zhejiang, Jilin and Ningxia Hui Autonomous Region. The quantitative data included de-identified DRTB registry data during 2015-2018 in project provinces from China CDC, medical records of DRTB patients registered in 2018 (n = 106) from designated hospitals, and a structured DRTB patient survey in six sample prefectures in 2019. The quality of clinical services was evaluated using seven indicators across patient screening, diagnosis and treatment. Logistic regression was conducted to explore factors associated with the extremely high financial burden. Semi-structured in-depth interviews with policymakers and focus group discussions with physicians and DRTB patients were conducted to understand the interventions implemented and their impacts. RESULTS: The percentage of bacterially confirmed patients taking a drug susceptibility test (DST) increased significantly between 2015 and 2018: from 57.4 to 93.6% in Zhejiang, 12.5 to 86.5% in Jilin, and 29.7 to 91.4% in Ningxia. The treatment enrollment rate among diagnosed DRTB patients also increased significantly and varied from 73 to 82% in the three provinces in 2018. Over 90% of patients in Zhejiang and Jilin and 75% in Ningxia remained in treatment by the end of the first six months' treatment. Among all survey respondents 77.5% incurred extremely high financial burden of treatment. Qualitative results showed that interventions on promoting rapid DST technologies and patient referral were successfully implemented, but the new financing policies for reducing patients' financial burden were not implemented as planned. CONCLUSIONS: The quality of DRTB related clinical services has been significantly improved following the comprehensive interventions, while the financial burden of DRTB patients remains high due to the delay in implementing financing policies. Stronger political commitment and leadership are required for multi-channel financing to provide additional financial support to DRTB patients.

Multi-source financing for tuberculosis treatment in China: key issues and challenges.

BACKGROUND: The End Tuberculosis (TB) Strategy of the World Health Organization highlights the need for patient-centered care and social protection measures that alleviate the financial hardships faced by many TB patients. In China, TB treatments are paid for by earmarked government funds, social health insurance, medical assistance for the poor, and out-of-pocket payments from patients. As part of Phase III of the China-Gates TB project, this paper introduces multi-source financing of TB treatment in the three provinces of China and analyzes the challenges of moving towards universal coverage and its implications of multi-sectoral engagement for TB care. MAIN TEXT: The new financing policies for TB treatment in the three provinces include increased reimbursement for TB outpatient care, linkage of TB treatment with local poverty alleviation programs, and use of local government funds to cover some costs to reduce out-of-pocket expenses. However, there are several challenges in reducing the financial burdens faced by TB patients. First, medical costs must be contained by reducing the profit-maximizing behaviors of hospitals. Second, treatment for TB and multi-drug resistant TB (MDR-TB) is only available at county hospitals and city or provincial hospitals, respectively, and these hospitals have low reimbursement rates and high co-payments. Third, many patients with TB and MDR-TB are at the edge of poverty, and therefore ineligible for medical assistance, which targets extremely poor individuals. In addition, the local governments of less developed provinces often face fiscal difficulties, making it challenging to use of local government funds to provide financial support for TB patients. We suggest that stakeholders at multiple sectors should engage in transparent and responsive communications, coordinate policy developments, and integrate resources to improve the integration of social protection schemes. CONCLUSIONS: The Chinese government is examining the establishment of multi-source financing for TB treatment by mobilization of funds from the government and social protection schemes. These efforts require strengthening the cooperation of multiple sectors and improving the accountability of different government agencies. All key stakeholders must take concrete actions in the near future to assure significant progress toward the goal of alleviating the financial burden faced by TB and MDR-TB patients.

Changes in newly notified cases and control of tuberculosis in China: time-series analysis of surveillance data.

BACKGROUND: China has made progress in tuberculosis control, but this disease remains a burden in many regions of China. We performed time-series analysis to examine changes in the rates of newly notified and newly smear-positive cases of tuberculosis in different regions of China from 1997 to 2018 and assessed the effect of the current control program. METHODS: National and provincial notification data on tuberculosis from 1997 to 2018, which covers 31 provinces in the mainland of China, were extracted from the Chinese public health science data center. The annual percentage changes in newly notified and smear-positive cases were analyzed using a joinpoint regression method. RESULTS: There were 18 646 672 newly notified tuberculosis cases from 1997 to 2018, with the greatest number in 2005. A total of 6 605 414 of these cases (35.42%) were smear-positive cases. The number of newly notified cases in China overall decreased (96.88-59.27 cases per 100 000) significantly during the most recent years. The decline during this period ranged from -3.9% (95% CI -5.7 to -2.9) in the western region to -4.3% (95% CI -4.8 to -3.7) in the eastern region. Most provinces had significant declines in newly notified and smear-positive cases, whereas the decline of newly smear-positive cases in Xinjiang was about half of that observed during the same period in China overall (-4.1% vs -9.9%). In addition to disparities in annual percentage changes, the rate of newly notified cases was higher in the western region than in the eastern and central regions. CONCLUSIONS: The burden of tuberculosis has been on declining throughout China during recent years, but tuberculosis in western China continues to be a public health emergency that needs to be urgently addressed. Effective prevention and control strategies are needed for regions with high disease burdens and those with increasing or unchanging numbers of newly notified and smear-positive cases of tuberculosis.

Dural sac cross-sectional area is a highly effective parameter for spinal anesthesia in geriatric patients undergoing transurethral resection of the prostate: a prospective, double blinded, randomized study.

BACKGROUND: Spinal anesthesia is optimal choice for transurethral resection of the prostate (TURP), but the sensory block should not cross the T10 level. With advancing age, the sensory blockade level increases after spinal injection in some patients with spinal canal stenosis. We optimize the dose of spinal anesthesia according to the decreased ratio of the dural sac cross-sectional area (DSCSA), the purpose of this study is to hypothesis that if DSCSA is an effective parameter to modify the dosage of spinal anesthetics to achieve a T10 blockade in geriatric patients undergoing TURP. METHODS: Sixty geriatric patients schedule for TURP surgery were enrolled in this study. All subjects were randomized divided into two groups, the ultrasound (group U) and the control (group C) groups, patient receive either a dose of 2 ml of 0.5% isobaric bupivacaine in group C, or a modified dose of 0.5% isobaric bupivacaine in group U. We measured the sagittal anteroposterior diameter (D) of the dural sac at the L3-4 level with ultrasound, and calculated the approximate DSCSA (A) according to the following formula: A = π(D/2)2, ( π = 3.14). The modified dosage of bupivacaine was adjusted according to the decreased ratio of the DSCSA. RESULTS: The cephalad spread of the sensory blockade level was significantly lower (P < 0.001) in group U (T10, range T7-T12) compared with group C (T3, range T2-T9). The dosage of bupivacaine was significantly decreased in group U compared with group C (P < 0.001). The regression times of the two segments were delay in group U compared with group C (P < 0.001). The maximal decrease in MAP was significantly higher in the group C than in group U after spinal injection (P < 0.001), without any modifications HR in either group. Eight patients in group C and two patients in group U required ephedrine (P = 0.038). CONCLUSIONS: The DSCSA is a highly effective parameter for spinal anesthesia in geriatric patients undergoing TURP, a modified dose of local anesthetic is a critical factor for controlling the sensory level. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800015566).on 8, April, 2018.

Cross-Sectional Seroepidemiologic Study of Coronavirus Disease 2019 (COVID-19) among Close Contacts, Children, and Migrant Workers in Shanghai.

(1) Background: Along with an increasing risk caused by migrant workers returning to the urban areas for the resumption of work and production and growing epidemiological evidence of possible transmission during the incubation period, a study of Coronavirus Disease 2019 (COVID-19) is warranted among key populations to determine the serum antibody against the SARS-CoV-2 and the carrying status of SARS-CoV-2 to identify potential asymptomatic infection and to explore the risk factors. (2) Method: This is a cross-sectional seroepidemiologic study. Three categories of targeted populations (close contacts, migrant workers who return to urban areas for work, and school children) will be included in this study as they are important for case identification in communities. A multi-stage sampling method will be employed to acquire an adequate sample size. Assessments that include questionnaires and blood, nasopharyngeal specimens, and feces collection will be performed via home-visit survey. (3) Ethics and Dissemination: The study was approved by the Institute Review Board of School of Public Health, Fudan University (IRB#2020-04-0818). Before data collection, written informed consent will be obtained from all participants. The manuscripts from this work will be submitted for publication in quality peer-reviewed journals and presented at national or international conferences.

A Modified Spontaneously Closed Defunctioning Tube Ileostomy After Anterior Resection of the Rectum for Rectal Cancer with a Low Colorectal Anastomosis.

The aim of this study is to introduce a new technique of modified spontaneously closed defunctioning tube ileostomy after anterior resection of the rectum for rectal cancer with a low colorectal anastomosis. Patients with rectal cancer who underwent anterior resection of rectum with a low colorectal anastomosis and chose a modified defunctioning tube ileostomy between March 2012 and August 2013 were retrospectively reviewed. Data on the success of the operation procedures, post-operative hospital stay, and post-operative tube ileostomy-related complications were analyzed. One hundred fifty-two patients (87 males and 65 females; 57.1 ± 17.4 years) undergoing the modified defunctioning tube ileostomy after anterior resection for rectal cancer were included. The post-operative hospital stay was 11.9 ± 3.2 days. The tube was removed on days 22.6 ± 4.1 after operation and the ileostomy wound closed spontaneously within 13.1 ± 1.9 days. Twenty-five patients felt tube-associated pain or discomfort, which was relieved after a period of adaptation and appropriate tube adjustment. Nine patients suffered from tube blockage and were treated successfully with saline irrigation. Two patients had intestinal obstruction, which was resolved with conservative treatment. Three patients developed leakage of the distal anastomosis: two were successfully treated with conservative measures and the other completely recovered after reoperation. The modified spontaneously closed defunctioning tube ileostomy appears efficacious and safe. This technique may be used to protect the distal anastomosis and simultaneously decrease the ileostomy complications, and minimize the morbidity and mortality associated with stoma takedown.

Schwannoma of the colon: A case report and review of the literature.

Colonic schwannomas are rare gastrointestinal mesenchymal tumors, and only a limited number of cases has been reported. The occurrence of these tumors is less common in the large intestine than in the stomach. The present study reports a case of colonic schwannoma in a 62-year-old female patient with no specific symptoms. The patient was diagnosed with a mass in the ascending colon by colonoscopy and abdominal computed tomography scanning. A right hemicolectomy was performed. The postoperative pathological diagnosis was ascending schwannoma. This case is noteworthy as colonic schwannomas are rare and are typically treated as colon cancer. No recurrence of the lesion was observed after 24 months of follow-up.

Multi-stage resection and repair for the treatment of adult giant sacrococcygeal teratoma: A case report and literature review.

Sacrococcygeal teratoma (SCT) is a sacrococcygeal neoplasm derived from more than one primitive germ layer and is only occasionally encountered in adults. The primary treatment for all primary SCTs is surgical excision. The present study reports the case of a giant SCT in a middle-aged female with a history lasting >3 decades. Multi-staged surgical treatment was performed, including ileostomy plus tumor excision, four debridement plus flap repair procedures, and closure of the ileostomy. Follow-up showed improved quality of life without evidence of local recurrence after resection. The study also presents a brief overview of the relevant literature. To the best of our knowledge, this is the first report of multi-staged surgical treatment for giant SCT in an adult patient.

Combined right hemicolectomy and pancreaticoduodenectomy for locally advanced right hemicolon cancer.

Extracolonic invasion of the duodenum and/or pancreatic head rarely occurs in patients with right hemicolon cancer. However, when necessary, combined radical operation is a challenge to the surgeon. We reported 7 patients with locally advanced right hemicolon cancer who underwent combined right hemicolectomy (RH) and pancreaticoduodenectomy (PD) due to direct involvement of the duodenum or pancreatic head. This study included four males and three females with a mean age of 66.9+/-5.9 years. Computed tomography (CT) scans revealed right hemicolon cancer with duodenal invasion (5 patients) and pancreatic invasion (2). The mean operation time was 410+/-64 minutes and the estimated blood loss was 514+/-157 mL. After the operation, the mean postoperative hospital stay was 22.1+/-7.2 days. Five patients had postoperative complications. The mean follow-up time was 16.4+/-5.9 months. During this period, three patients died from tumor recurrence, one from postoperative complications, one from pulmonary disease, and two survived until the last scheduled follow-up. Five patients survived more than one year. Combined RH and PD for locally advanced right hemicolon cancer can be performed safely, thus providing a long-term survival rate in selected patients in a high-volume center.

Over-expression of the MxIRT1 gene increases iron and zinc content in rice seeds.

Iron and zinc are essential in plant and human nutrition. Iron deficiency has been one of the causes of human mortality, especially in developing countries with high rice consumption. MxIRT1 is a ferrous transporter that has been screened from an iron-efficient genotype of the apple tree, Malus xiaojinensis Cheng et Jiang. In order to produce Fe-biofortified rice with MxIRT1 to solve the Fe-deficiency problem, plant expression vectors of pCAMBIA1302-MxIRT1:GFP and pCAMBIA1302-anti MxIRT1:GFP were constructed that led to successful production of transgenic rice. The transgenic plant phenotypes showed that the expression of endogenous OsIRT1 was suppressed by anti-MxIRT1 in antisense lines that acted as an opposing control, while sense lines had a higher tolerance under Zn- and Fe-deficient conditions. The iron and zinc concentration in T3 seeds increased by three times in sense lines when compared to the wild type. To understand the MxIRT1 cadmium uptake, the MxIRT1 cadmium absorption trait was compared with AtIRT1 and OsIRT1 in transgenic rice protoplasts, and it was found that MxIRT1 had the lowest Cd uptake capacity. MxIRT1 transgenic tobacco-cultured bright yellow-2 (BY-2) cells and rice lines were subjected to different Fe conditions and the results from the non-invasive micro-test technique showed that iron was actively transported compared to cadmium as long as iron was readily available in the environment. This suggests that MxIRT1 is a good candidate gene for plant Fe and Zn biofortification.

An uncleaved signal peptide directs the Malus xiaojinensis iron transporter protein Mx IRT1 into the ER for the PM secretory pathway.

Malus xiaojinensis iron-regulated transporter 1 (Mx IRT1) is a highly effective inducible iron transporter in the iron efficient plant Malus xiaojinensis. As a multi-pass integral plasma membrane (PM) protein, Mx IRT1 is predicted to consist of eight transmembrane domains, with a putative N-terminal signal peptide (SP) of 1-29 amino acids. To explore the role of the putative SP, constructs expressing Mx IRT1 (with an intact SP) and Mx DsIRT1 (with a deleted SP) were prepared for expression in Arabidopsis and in yeast. Mx IRT1 could rescue the iron-deficiency phenotype of an Arabidopsis irt1 mutant, and complement the iron-limited growth defect of the yeast mutant DEY 1453 (fet3fet4). Furthermore, fluorescence analysis indicated that a chimeric Mx IRT1-eGFP (enhanced Green Fluorescent Protein) construct was translocated into the ER (Endoplasmic reticulum) for the PM sorting pathway. In contrast, the SP-deleted Mx DsIRT1 could not rescue either of the mutant phenotypes, nor direct transport of the GFP signal into the ER. Interestingly, immunoblot analysis indicated that the SP was not cleaved from the mature protein following transport into the ER. Taken together, data presented here provides strong evidence that an uncleaved SP determines ER-targeting of Mx IRT1 during the initial sorting stage, thereby enabling the subsequent transport and integration of this protein into the PM for its crucial role in iron uptake.

[A prevalence investigation of blindness and vision impairment in 2009 in older adults of Dachang Blocks of Baoshan District, Shanghai, China].

OBJECTIVE: To investigate the prevalence of blindness and low vision and the leading causes of blindness in residents aged≥60 years in Dachang Blocks of Baoshan District, Shanghai, China. METHODS: A cross-sectional study was carried out by Shanghai Eye Disease Prevention & Treatment Center and the Center for Disease Control and Prevention in Baoshan District of Shanghai from October to December in 2009. Randomly cluster sampling was used to identify the adults aged≥60 years who had lived in Dachang Blocks of Baoshan District, Shanghai for more than 10 years. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) based on autorefraction and subjective refraction were measured separately in each eye. External eye, anterior segment and ocular fundus were examined by the ophthalmologist using slit lamp-microscopes direct ophthalmoscopy and non-mydriatic digital camera. And the leading causes of visual impairment were assured. The Chi square test was used between the groups of rate comparison. RESULTS: Of 5199 enumerated subjects≥60 years of age, 87.42% (4545/5199) were examined. All subjects were urban population who were originally changed from the rural population in nearly 10 years. In this population, with best-corrected visual acuity, 30 persons were diagnosed as blindness, 145 persons were diagnosed as low vision. The prevalence of blindness and low vision were 0.67%, 3.19%, respectively. Low vision was associated with female gender. It was statistically significant difference (χ2=4.88, P<0.05). The leading causes of blindness were cataract, macular degeneration, ocular absence or atrophy, glaucoma, and diabetic retinopathy or corneal diseases. With presenting visual acuity, 39 persons were diagnosed as blindness, 401 persons were diagnosed as low vision. The prevalence of blindness and low vision were 0.86%, 8.82%, respectively. Blindness and low vision were associated with older age. The prevalence of blindness and low vision increased rapidly in aged 75 years or older people. The leading causes of blindness were cataract, uncorrected refractive error, macular degeneration, ocular absence or atrophy, glaucoma. Low vision was associated with female gender. It had statistically significant difference (χ2=13.345, P<0.01). CONCLUSIONS: In rapidly urbanized and aging community of Shanghai, cataract, uncorrected refractive error, macular degeneration were the leading causes of blindness with presenting visual acuity. The prevalence of low vision in females was higher than that of males which had statistically significant difference. These kinds of residents needed more targeted eye health education and services.

[The cluster and drug-resistant characteristics of Beijing genotype Mycobacterium tuberculosis in eastern rural China].

OBJECTIVE: To investigate the distribution of Mycobacterium tuberculosis (MTB) Beijing genotype, which was isolated from tuberculosis (TB) patients registered in local TB dispensaries in Deqing and Guanyun county respectively within 1 year, as well as its drug-resistant phenotypic and genotypic profiles and genotyping features. METHODS: A total of 399 TB patients were enrolled from 2 counties. Of the 351 TB patients with MTB isolates available, 237 were male, and 114 were female; aged from 18 - 82 (46 ± 35) years. The proportion method and DNA sequencing were used to define the susceptibility of the isolates to 4 first line anti-TB drugs and the related mutation. Beijing genotype MTB strains were identified by Spoligotyping, while the "cluster" strains and the "unique" strains were defined by IS6110 restriction fragment length polymorphism (RFLP). RESULTS: Beijing genotype MTB strains were identified in 243 of the 351 strains isolated, and the proportion of multi-drug resistance, mono-resistance to rifampin and isoniazid among Beijing genotype MTB was 18.5% (45/243), 43.2% (105/243) and 22.2% (54/243) respectively, all being significantly higher than the non-Beijing genotype MTB, 7.4% (8/108), 24.1% (26/108) and 12.0% (13/108) respectively. katG and rpoB mutations were observed more common among Beijing genotype MTB than among non-Beijing genotype MTB, 13.2% (32/243) and 4.6% (5/108) respectively, OR = 2.553, 95%CI: 1.031 - 6.324. The Beijing genotype MTB was more likely to be clustered than non-Beijing genotype MTB, 41.2% (100/243) and 11.1% (12/108) respectively, OR = 5.503, 95%CI: 2.851 - 10.622. CONCLUSIONS: In eastern rural China, TB patients infected with the Beijing genotype MTB may have a higher risk to develop isoniazid-or rifampin-resistance and multi-drug resistance. The disease is more likely due to recent transmission.

[Molecular-epidemiological study on the transmission of drug resistant tuberculosis and its influencing factors in rural areas of eastern China].

OBJECTIVE: To investigate the contribution of recent transmission in the epidemic of drug-resistant Mycobacterium tuberculosis (M.TB) and related factors from biomedical and social-demographic perspectives in the Eastern rural areas of China. METHODS: Identified by proportion method of drug susceptibility test, 223 drug resistant M.TB isolates and their hosts were included in the present study. These drug resistant tuberculosis isolates were first genotyped by Mycobacterial Interspersed Repetitive Units (MIRU), and those isolates with identical MIRU genotype were further classified by IS6110 restricted fragment polymorphism (RFLP). 'Cluster' was defined as two patients' M. TB isolates harboring the identical MIRU genotype and IS6110-based RFLP pattern simultaneously. Unique strains denoted those with the unparalleled MIRU genotype in the study collection. Socio-demographic and biomedical characteristics of host patients were compared between the clusters and unique groups through univariate and multivariate logistic regression analysis. RESULTS: Based on the MIRU-IS6110 pattern, there were 52 isolates belonged to the "cluster" group and 171 as the "unique" group. Drug resistant M.TB strain isolated from patients at the age of 30 - 60 year had a higher probability of being clustered, comparing to those from patients below 30 years of age (30.9% vs. 11.9%; OR = 3.297; 95%CI: 1.169 - 9.297). Such finding were also seen in the isolates from patients with previous treatment history compared to newly diagnosed patients (32.9% vs. 18.4%; OR = 2.163, 95%CI: 1.144 - 4.090). The multi-drug resistant M.TB strain was found to have been more frequently clustered when comparing to the mono-drug resistant M.TB (47.2% vs. 15.5%; OR = 4.773; 95%CI: 2.316 - 9.837). The transmission pattern of drug resistant tuberculosis was presented mainly by the sporadic distribution in small group within rural villages. CONCLUSION: Transmission of drug-resistant tuberculosis was seen in the population living in the Eastern rural areas of China, and causal contact within villages was considered as the main route of recent transmission. Patients at middle age and having previous tuberculosis treatment history might have increased the risk of transmission by patients with drug resistant tuberculosis.

[The combined application of multiple genotyping methods in identifying genotypes of Mycobacterium tuberculosis strain circulating in rural China].

OBJECTIVE: To evaluate the performance of MIRUs (mycobacterial interspersed repetitive units) genotyping alone, IS6110-RFLP (IS6110 restriction fragment length polymorphism) genotyping alone and their combination applied in the molecular epidemiological study of Mycobacterium tuberculosis (MTB) isolates circulating in rural China. METHODS: A cross-sectional study was designed to collect MTB isolates from the TB patients registered in local TB dispensaries of Deqing county and Guanyun county from 2004 to 2005. The proportion method was used to determine drug susceptibility of MTB isolates to the first line anti-TB drugs (isoniazid, rifampin, ethambutol and streptomycin). The Beijing family of MTB was identified by Spoligotyping. All isolates were genotyped by MIRUs alone, IS6110-RFLP alone and their combination. RESULTS: Of the 351 studied MTB isolates, 243 (69.2%) had the genotypes that belonged to the Beijing family, and 223 (63.5%) were resistant to at least 1 anti-TB drug, including 53 (15.1%) resistant to isoniazid and rifampin simultaneously or multidrug resistant (MDR). The heterogeneity of 12 MIRUs loci differed from 0.76 in MIRU26 to 0.003 in MIRU2. MIRUs alone identified 235 genotypes (HGI = 0.9317), including 46 "clusters" containing 162 isolates and 189 "unique" pattern/isolates. Thirty-eight isolates comprised the largest MIRUs defined cluster and presented MIRUs type 2233 2517 3533. MIRUs based clusters were further identified by IS6110-RFLP into 28 subgroups containing 80 isolates (HGI = 0.9989). In comparison, IS6110-RFLP determined 267 genotypes from all isolates, including 46 "clusters" containing 130 isolates (HGI = 0.9684) and 221 "unique" pattern/isolates. All the 46 IS6110-RFLP defined clusters could also be further identified by MIRUs into 31 subgroups (HGI = 0.9992). The performance of MIRUs prior to IS6110-RFLP combination was comparable to that of IS6110-RFLP prior to MIRUs combination, especially in Beijing genotype strain (HGI: 0.9930 vs 0.9933) and MDR-TB strains (HGI: 0.9965 vs 0.9963). CONCLUSION: For feasibility, cost and discriminatory power, MIRUs prior to IS6110-RFLP combination is more suitable for the massive epidemiological investigation of MTB in rural China.

Incidental gallbladder carcinoma diagnosed during or after laparoscopic cholecystectomy.

BACKGROUND: Gallbladder carcinoma (GC) is a highly lethal neoplasm. With the increase of cholecystectomies since the wide acceptance of laparoscopic cholecystectomy (LC), the incidental diagnosis of gallbladder carcinoma is more frequent. The aim of the present study was to report our experience with GC diagnosed during or after the performance of LC. METHODS: A total of 10,466 LCs were carried out from January 1999 to December 2007 in our hospital. Records of patients with incidental carcinoma were collected and analyzed retrospectively. RESULTS: Of all the patients, 20 (0.19%) were histopathologically diagnosed as having a GC. There were 4 men and 16 women; the median age in this group was 65.7 years (range: 37-81 years).The depth of cancer invasion was: pTis (4 cases), pT1a (2 cases), pT1b (2 cases), pT2 (6 cases), pT3 (4 cases), and pT4 (2 cases). The sensitivity and specificity of intraoperatively frozen section examination were 83.3 and 100%, respectively. Patients with in situ, pT1a and pT1b tumors underwent LC only, and there were no recurrences. The survival rate between patients with GC diagnosed during or after LC showed no difference; it was dependent on the depth of cancer invasion. CONCLUSIONS: The survival with incidental GC is related to stage, and it validates that a carefully performed LC is adequate treatment for carcinoma in situ, and stage 1a and b cancer. A frozen section examination was helpful but did not provide a definitive diagnosis. Meticulous techniques during LC, including retrieval of the gallbladder in a retrieval bag, may prevent port-site recurrence and intraperitoneal dissemination.

[Population-based molecular epidemiologic study of rifampicin-resistant tuberculosis in rural area of eastern China].

OBJECTIVE: To describe the drug resistance-related molecular characterization and clustering feature of rifampicin-resistant (RIFr) M.tuberculosis (M.tb) in rural area of eastern China. METHODS: All patients diagnosed as RIFr M.tb in Deqing and Guanyun county during one year period from 2004 to 2005 were included in the study. By proportion method of drug susceptibility test, 65 isolates were identified resistant to rifampicin and regarded as the studied strains. Hotspots of rpoB gene and katG gene were detected by direct DNA sequencing. Beijing genotype M.tb strains were identified by spoligotyping. IS6110-RFLP (IS6110 restriction fragment length polymorphism) and clustering analysis were performed on all RIFr M.tb isolates available. RESULTS: The mutations in 81 bp rifampicin-resistance determination region (RRDR) of the rpoB gene were observed among 60 (92%) RIFr M.tb isolates, with mutation in locus 531 observed in the majority of RIFr isolates (37/65). 49 (82%) of the 60 isolates were multidrug resistant TB (MDR-TB), which were referred to as resistant to both RIF and isoniazid (INH). Through spoligotyping, 54(83%) isolates were identified as Beijing genotype strains. In clustering analysis of IS6110-RFLP, 24 isolates were grouped into 11 clusters, suggesting that the recent transmission of M.tb did exist among patients. Regarding the drug resistance profile in clusters, all the isolates in clusters were also MDR-TB. 7 clusters contained isolates carrying different mutations were related to RIF-resistance. Multivariate analysis showed the proportion of new cases in clustered patients is higher than that in the un-clustered patients (new/previously treated: OR = 3.342; 95%CI: 1.081 - 10.32). CONCLUSION: The acquisition of rifampicin resistance in M.tb was more likely to be resulted from the selective growth of RIFr M.tb in the specific drug resistant M.tb such as isoniazid-resistant M.tb. Previous elongated irregular treatment might favor the epidemic of RIFr M.tb.