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Objectives Bedaquiline treatment significantly improves multidrug-resistant tuberculosis (MDR-TB) patient treatment outcomes. However, safety and efficacy data are lacking for bedaquiline used with background regimens to treat Chinese TB patients. Here, we describe our initial clinical experience for bedaquiline treatment of a large multicentre cohort of MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patients in China. Methods Patients (177) received 24-week bedaquiline treatment combined with personalized anti-TB drug background regimens. As primary efficacy endpoints, times to initial sputum culture conversion were measured. Results Of 177 MDR-TB patients completing the 24-week treatment course, sputum culture conversion occurred for 151/177 (85.3%), while 26 had unfavourable outcomes, including 3/177 (1.7%) deaths and 23/177 (13.0%) non-responders at treatment completion. The median time to sputum culture conversion was 4 (interquartile range 2–8) weeks. Conversion rates were 33/39 (84.6%, 95% confidence interval (CI) 73.3–95.9) for MDR-TB patients, 47/56 (83.9%, 95% CI 74.3–93.6) for pre-XDR-TB patients and 71/82 (86.6%, 95% CI 79.2–94.0) for XDR-TB patients. Multivariate analysis demonstrated that patients with low body mass index (odds ratio 7.356; 95% CI 2.652–20.401) were at significantly high risk of unfavourable outcomes, with serious adverse events noted in 15 (8.5%) patients, including six with corrected QT interval (QTc) prolongation times (>500 ms). Conclusion Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion.

Objectives Diffusion tensor imaging (DTI) has been used to detect microstructural alteration and effect of surgical treatment of the trigeminal nerve root (TR) in patients with classical trigeminal neuralgia (CTN) underwent microvascular decompression (MVD). Patients with CTN without neurovascular compression (woNVC) is a special population of TN, however, the pathogenesy of CTN woNVC and the mechanism of internal neurolysis (IN) remain unknown. Materials and methods 21 patients with CTN woNVC who underwent IN and 20 healthy controls were included in this study. The differences in the means, kurtosis and skewness of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between the affected and unaffected nerves in patients and both nerves in controls were investigated by independent t-test and paired t-test respectively. Longitudinal changes of FA and ADC were correlated with outcome of IN via Spearman correlation coefficient. Results Significant differences were found in preoperative mean and kurtosis values for both FA and ADC of the affected side TR, compared to the unaffected side and control group respectively. However, these differences remarkably reduced postoperatively. Further, the Spearman correlation coefficient showed a strong negative correlation between decrease of ADC in the affected side and the surgical outcome in BNI total score. Conclusion The changes of diffusive property of TR, especially the FA and ADC, provide alternative radiological evidence for evaluating the mechanism of CTN woNVC. The modification of DTI metrics could be an effective factor for providing potential noninvasive biomarkers for determining the prognosis of patients with CTN woNVC underwent IN.

Objective: To investigate the efficacy and safety of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia in elderly patients. Methods: We retrospectively analysed data ...

Letter to the Editor

Background and Objective Trigeminal neuralgia is a common neurologic disease that seriously impacts a patient's quality of life. We retrospectively investigated the efficacy and safety of internal neurolysis (nerve combing) for trigeminal neuralgia without vascular compression. Patients and Methods This study was a retrospective review of all patients with trigeminal neuralgia who were admitted between January 2014 and February 2019. A subgroup of 36 patients had no vascular compression at surgery and underwent internal neurolysis. Chart review and postoperative follow-up were performed to assess the overall outcomes of internal neurolysis. Results Thirty-six patients were identified, with a mean age of 44.89 ± 7.90 (rang: 31–65) years and a disease duration of 5.19 ± 2.61 years. The immediate postoperative pain relief (Barrow Neurological Institute [BNI] pain score of I or II) rate was 100%. The medium- to long-term pain relief rate was 91.7%. Three patients experienced recurrence. Facial numbness was the primary postoperative complication. Four patients with a score of III on the BNI numbness scale immediately after surgery had marked improvement at 6 months. No serious complications occurred. Conclusion Internal neurolysis is a safe and effective treatment for trigeminal neuralgia without vascular compression or clear responsible vessels.

Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

We report a case of cholesteatoma that caused left facial pain with facial numbness. The tumour was located in the left cerebellopontine angle (CPA) and Meckel's cave. A balloon was first placed into Meckel's cave, and then, under electrophysiological monitoring, the tumour within the CPA cistern was resected via the retrosigmoid approach. The balloon was inflated in Meckel's cave to push the tumour out of Meckel's cave, and then, the tumour was completely removed under endoscopy. The symptoms, including pain and numbness, subsided after surgery.

Objective The clinical data of patients with hemifacial spasm (HFS) were analyzed statistically to identify factors leading to delayed cure after microvascular decompression (MVD). Methods A retrospective analysis of the clinical data of 600 patients with HFS subjected to MVD from March 2016 to May 2018 was performed. Student t test, chi-square test, logistic regression analysis, and multivariate analysis of variance were used to analyze the correlation between delayed cure and its related factors. Results Among the 600 patients enrolled, 117 had delayed cure after MVD. The shortest duration of delayed cure was 4 days, and the longest was 540 days, with an average of 108 days. The frequency of delayed improvement in these patients was not associated with sex, age, or offending vessel type (p > 0.05); however, delayed cure was positively correlated with the course of the disease, grade of HFS severity, and disappearance of abnormal muscle responses during the operation (p Conclusion MVD is an effective treatment for HFS. Given that postoperative delayed cure was unavoidable, even with accurate identification of the offending vessel and sufficient decompression of the root exit zone, delayed cure should be considered in patients undergoing reoperation due to lack of remission or relapse after the operation. Additionally, the timing of efficacy assessments should be delayed.

The regional brand is of great significance to the development of industrial clusters. The industrial scale with bigger clusters is the basis to form the regional brands and the cultivation of business brand is the important support for the regional brands. The building of the benign interaction mechanism between the regional brands and the business brands is the core of the brand strategy of industrial clusters. The governance of the “tragedy of the commons” of brands is the key to prevent the risk of regional brands. At the same time, the guidance of local government and the service of intermediaries can provide a favorable environment for the building of regional brands

Background. Canaliculitis may cause punctal or canalicular swelling, discharge, erythema, and sometimes concretions. This study examined the clinical characteristics, treatment patterns, and outcomes of primary canaliculitis from patients at a top-rated hospital in Beijing, China.Methods. Medical records of 16 patients (retrospective case series) were studied.Results. This study included four males and twelve females with a median age of 72.5 years. The mean and the median follow-up time were 10.4 months and 6 months, respectively. The mostly observed clinical symptoms were epiphora with discharge (94%), while the mostly observed signs included pouting punctum (75%) and punctal regurgitation of concretions under syringing (75%). Only the symptoms of one patient among those with conservative therapy completely resolved within two-year follow-up. Curettage therapy was found to partly resolve the clinical symptoms and signs within the follow-up of four weeks. Fifteen patients finally received curettage with punctoplasty, and symptoms completely resolved in fourteen patients after one surgery.Conclusions. Syringing with pressing of lacrimal sac area may help better diagnosis of canaliculitis. Additionally, curettage with punctoplasty is recommended for thorough removal of concretions and complete resolution of canaliculitis.

To explore the clinical significance of cytometric bead array(CBA) in detecting partial cytokines(IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ)in the serum from patients with different types of pulmonary tuberculosis.The levels of six cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) in the serum from 84 cases of patients with pulmonary tuberculosis(46 cases of active pulmonary tuberculosis patients, 38 cases of inactive pulmonary tuberculosis patients) and 30 cases of normal person, were detected by BD CBA Flex Set kit.The levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in pulmonary tuberculosis group were significantly higher than those in control group (P0.01 or P0.05.Compared with the inactive pulmonary tuberculosis group, the levels of serum IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in the active pulmonary tuberculosis group were significantly higher (P0.01 or P0.05).Serum IL-4 and TNF-α levels in active pulmonary tuberculosis group, inactive pulmonary tuberculosis group and the control group had not significantly different.Six cytokines in serum can be detected quickly and sensitively in batches at one time by CBA. IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ play an important role in the immune pathogenesis of pulmonary tuberculosis.

Glioblastoma multiforme (GBM) is the most lethal type of brain tumor. The formation of abnormal, dysfunctional tumor vasculature and glioblastoma stem-like cells (GSCs) are believed to be the major components of the inability to treat these tumors effectively. We analyzed 70 glioblastoma samples by immunohistochemistry and double immunofluorescence staining. The immunohistochemical expression of the putative brain tumor stem cell markers CD133 and Nestin in paraffin sections was analyzed using morphometry. In all GBM samples, CD133 or Nestin was expressed in tumor and endothelial cells. Double immunofluorescence stainings showed that the two different marked GSCs were found accumulated around the CD31+ blood vessels and CD133/CD31 or Nestin/CD31 co-expression was found in the endothelial cells and GSCs. Furthermore, the vascular endothelial growth factor (VEGF) and the endothelial marker CD31 were co-expressed in GSCs. Therefore, GSCs not only showed distinct perivascular distribution but were capable of differentiating into endothelial cells. We demonstrate that GSCs contribute directly to the tumor vasculature by endothelial cell differentiation. GSCs and tumor vascularization are closely related to each other, not only in the regional distribution but also in biological function. These findings describe a new mechanism for tumor vasculo-genesis and may provide new insights for targeted therapy against brain tumors.

Brain tumor stem cells (BTSC) are predicted to be critical drivers of tumor progression due to their self-renewal capacity and limitless proliferative potential. Recent studies suggest that stem cells are controlled by a particular microenvironment known as a “niche”. We therefore analysed human glioma tissues and found that the CD133 + and nestin + niches are perivascularly localized in all glioma tissues. Furthermore, there is a positive correlation between the CD133 + niches and CD133 + blood vessels, which is similar to the correlation between the nestin + niches and nestin + blood vessels. We demonstrate that both CD133 + blood vessels and nestin + blood vessels have an important role in maintaining the structure of the glioma stem cell niche. Moreover, the abundance of CD133 + niches and nestin + niches increases significantly as tumor grade increases. These findings provide a new insight into the biology of BTSC and open a new perspective for targeted therapy against the brain tumors.

To investigate the expressions of putative brain tumor stem cell (BTSC) marker CD133, Nestin and blood vessel endothelial cell marker CD31 in 65 cases of formalin fixed paraffin embedded gliomas. The relationship of BTSC distribution with micro-blood vessels was analyzed using morphometry.(1) The expression levels of Nestin and CD133 proteins were detected using SABC immunohistochemical analysis. Then we calculated the percentage of CD133(+) cells, CD133(+) blood vessels, Nestin(+) cells and Nestin(+) blood vessels among 65 tumors, grade II (n = 18), grade III (n = 23) and grade IV (n = 24), according to WHO 2000 classification of nervous system tumors. (2) Double immunofluorescence staining was used to detect the co-expressions of CD133/CD31, CD133/Nestin and Nestin/CD31. Then the correlation of two different marked cells with the corresponding positive vascular endothelial cells were determined.CD133(+) cells and Nestin(+) cells could be observed in all glioma tissues. Furthermore they could also be observed expressing in the endothelial cells. In low-grade group, there were fewer CD133(+) blood vessels or Nestin(+) blood vessels in the regions which CD133(+)cells or Nestin(+) cells distributed compared with the high-grade group. The CD133(+)/CD31(+) and Nestin(+)/CD31(+) cells could be found co-expressed in the endothelial cells by using double immunofluorescence staining. Positive correlation was observed between the CD133(+) cells and CD133(+) blood vessels (r = 0.945, P0.01). It was similar to the correlation between the Nestin(+) blood vessels and Nestin(+) cells (r = 0.727, P0.01).In gliomas, the endothelial cells express brain tumor stem cells markers. Therefore the capillaries in gliomas may come from the differentiation of BTSCs. And the BTSCs are accumulated around the capillaries. Along with the rank of tumor grades, positive correlation is observed between CD133(+) cells or Nestin(+) cells with the corresponding blood vessels.

Purpose To study the effect on visual acuity of surgical management of late capsular block syndrome (CBS) and the possible complications. Setting Department of Ophthalmology, Peking University People's Hospital, Beijing, China. Methods In this retrospective observational series, records of patients who had late postoperative CBS and surgical management between January 2006 and December 2009 at the same hospital were drawn from a computerized database and reviewed. The patient's baseline characteristics, corrected distance visual acuity, and intraocular pressure (IOP) before and after the surgery were analyzed. Results Corrected distance visual acuity improved after the surgery in all patients. No risk for increased IOP or phacoanaphylaxis endophthalmitis was noted. Conclusion Initial findings with this surgical procedure indicate a potential treatment for late CBS; however, additional studies are needed before a firm conclusion can be drawn. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

We report the case of a 76-year-old Chinese man who had uneventful cataract phacoemulsification and hydrophilic acrylic intraocular lens (IOL) implantation 6 years previously. He presented with decreased vision; a homogeneous milky substance was found between the posterior chamber IOL and the posterior capsule without IOL displacement or a change in the refractive status. The milky substance was aspirated from the capsular bag. Biochemical analysis showed the concentrations of proteins and Ca(++) in the milky liquid were higher than those in the aqueous humor. Protein identification by mass spectrometry indicated that the milky liquid contained a high concentration of alpha-crystallin and beta-crystallin.

To investigate the effect of nutritional support on immunity function in the acquired immune deficiency syndrome (AIDS) patients.Sixty-five AIDS patients were randomly divided into treatment group (n=35) and control group (n=30). In the treatment group, the patients received enteral nutrition (EN) treatment or EN supplemented with parenteral nutrition (EN+PN) on top of routine treatment according to the daily condition of the sufferers. The control group received routine treatment only. CD3, CD4 and CD8 cell, CD4/CD8, C3, C4, immunoglobulin G (IgG), IgM, IgA were determined on the 0 and 30th day of the treatment, and they were analyzed with covariance analysis.CD4 cell in the treatment group was significantly raised compared with before examination (P0.05). Other immunity indexes were not correlated. All clinical indexes showed no change in the control group (all P0.05).The nutritional support can raise the immunity function in the AIDS patient.

Objective To investigate the effect of all-trans retinoic acid(ATRA) on the proliferation and differentiation of brain tumor stem cells(BTSCs) in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP) in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS) were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P < 0.01). In serum-containing medium, the expression percentages of CD133 and GFAP in the differentiated BTSCs were (2.29% ± 0.27%) and (75.60% ± 4.03%) respectively in the ATRA group, and (7.05% ± 0.49%) and (12.51% ± 0.77%) respectively in the control group. The differentiation rate of BTSCs in the ATRA group was significantly higher than that in the control group (P < 0.05), but there was still CD133 expressed in the ATRA group. The differentiated BTSCs could re-form BTSs in serum-free medium. The percentage of BTS formation in the ATRA group was(4.84% ± 0.32%), significantly lower than that in the control group (17.71% ± 0.78%) (P < 0.05), and the time required for BTS formation in the ATRA group was (10.07 ± 1.03)d, significantly longer than that in the control group (4.08 ± 0.35)d (P < 0.05). Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.