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Therapeutic effects of thalidomide in hematologic disorders: a review
Miao Xu, Yu Hou, Lei Sheng, Jun Peng
Front Med. 2013, 7 (3): 290-300.
https://doi.org/10.1007/s11684-013-0277-z
The extensive autoimmune, anti-inflammatory, and anticancer applications of thalidomide have inspired a growing number of studies and clinical trials. As an inexpensive agent with relatively low toxicity, thalidomide is regarded as a promising therapeutic candidate, especially for malignant diseases. We review its therapeutic effects in hematology, including those on multiple myeloma, Waldenstroem macroglobulinemia, lymphoma, mantle-cell lymphoma, myelodysplastic syndrome, hereditary hemorrhagic telangiectasia, and graft-versus-host disease. Most studies have shown satisfactory results, although several have reported the opposite. Aside from optimal outcomes, the toxicities and adverse effects of thalidomide should also be examined. The current work includes a discussion of the mechanisms through which the novel biological effects of thalidomide occur, although more studies should be devoted to this aspect. With appropriate safeguards, thalidomide may benefit patients suffering from a broad variety of disorders, particularly refractory and resistant diseases.
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Diffuse cystic lung diseases
Jay H. Ryu, Xinlun Tian, Misbah Baqir, Kaifeng Xu
Front Med. 2013, 7 (3): 316-327.
https://doi.org/10.1007/s11684-013-0269-z
Diffuse cystic lung diseases are uncommon but can present a diagnostic challenge because increasing number of diseases have been associated with this presentation. Cyst in the lung is defined as a round parenchymal lucency with a well-defined thin wall (<2 mm thickness). Focal or multifocal cystic lesions include blebs, bullae, pneumatoceles, congenital cystic lesions, traumatic lesions, and several infectious processes such as coccidioidomycosis, Pneumocystis jiroveci pneumonia, and hydatid disease. “Diffuse” distribution in the lung implies involvement of all lobes. Diffuse lung involvement with cystic lesions can be seen in pulmonary lymphangioleiomyomatosis, pulmonary Langerhans’ cell histiocytosis, lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, amyloidosis, light chain deposition disease, honeycomb lung associated with advanced fibrosis, and several other rare causes including metastatic disease. High-resolution computed tomography of the chest helps define morphologic features of the lung lesions as well as their distribution and associated features such as intrathoracic lymphadenopathy. Correlating the tempo of the disease process and clinical context with chest imaging findings serve as important clues to defining the underlying nature of the cystic lung disease and guide diagnostic evaluation as well as management.
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The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report
Enfu Chen, Fenjuan Wang, Huakun Lv, Yanjun Zhang, Hua Ding, Shelan Liu, Jian Cai, Li Xie, Xiaoping Xu, Chengliang Chai, Haiyan Mao, Jimin Sun, Junfen Lin, Zhao Yu, Lianhong Li, Zhiping Chen, Shichang Xia
Front Med. 2013, 7 (3): 333-344.
https://doi.org/10.1007/s11684-013-0275-1
This study reports the first death caused by a novel avian influenza A (H7N9) virus in Zhejiang Province, China. The patient had chronic hepatitis B and history of exposure to poultry. The patient initially complained of diarrhea and influenza-like symptoms on March 7 and 14 respectively. The disease progressed to severe pneumonia, sustained hypoxia, and coagulation abnormalities. The patient died on March 27 because of respiratory failure, multiple organ failure, and disseminated intravascular coagulation without oseltamivir treatment. This H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai, Jiangsu, Anhui, etc. Analysis of hemagglutinin, neuramidinase, and matrix genes indicated that the isolates share the same avian origin, have low virulence, and are sensitive to oseltamivir, but are resistant to adamantine. Only the isolate that caused the fatality exhibited substitution of Q226I in the HA gene, which indicates a potentially enhanced human affinity. The secondary transmission rate was 1.6% (2/125). Only two health workers presented with influenza-like symptoms, and they subsequently tested negative for H7N9 RNA. In conclusion, underlying disease, late diagnosis, and untimely antiviral treatment are possible high-risk factors for infections and death caused by the low-pathogenicity avian influenza A (H7N9). Person-to-person transmission of the H7N9 virus was not detected among close contacts, but such transmission should be investigated in the future. Expanding and enhancing surveillance will help in the early discovery and diagnosis of suspected cases, which will reduce the number of severe cases and deaths.
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Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells: a preclinical study
Siming Yang, Kui Ma, Changjiang Feng, Yan Wu, Yao Wang, Sha Huang, Xiaobing Fu
Front Med. 2013, 7 (3): 345-353.
https://doi.org/10.1007/s11684-013-0282-2
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess various advantageous properties, including self-renewal, extended proliferation potential, multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions. However, little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs. In this study, we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media (ASFCM) in order to determine their potential for differentiation into sweat gland-like cells. We found that primary cultures of hUC-MSCs could be established with ASFCM. Moreover, cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum (FBS). Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions, and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29, CD44, CD90, and CD105, and negative for CD34 and CD45, as expected. Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions. Like normal cultured MSCs, hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers (CEA, CK14 and CK19) and developmental genes (EDA and EDAR) that are characteristic of normal sweat gland cells. Taken together, our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.
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Treatment outcomes of pulmonary tuberculosis in the past decade in the mainland of China: a meta-analysis
Xiangwei Li, Yu Yang, Jianmin Liu, Feng Zhou, Wei Cui, Ling Guan, Fei Shen, Cong Gao, Mufei Li, Qi Jin, Lei Gao
Front Med. 2013, 7 (3): 354-366.
https://doi.org/10.1007/s11684-013-0257-3
Due to the implementation of directly observed treatment strategy (DOTS), China has made a significant achievement in tackling the tuberculosis (TB) epidemic in the 1990s. However, only half of regions in China met or exceeded the 85% rate of treatment success target. The aim of the present study is to summarize the treatment outcomes of smear-positive pulmonary TB in the mainland of China in the past decade using meta-analysis based on systematic review of published observational studies. A total of 50 eligible articles (58 studies) were identified and included in this study. The summarized treatment success rates were 93.9% (95% CI, 92.8%–94.7%) for new cases and 85.4% (95% CI, 83.0%–87.6%) for previously treated cases, and the summarized cured rate were 92.2% (95% CI, 90.9%–93.3%) and 81.2% (95% CI, 79.1%–83.1%), respectively. A remarkable increase of rates for treatment success and cure was observed in the 1990s. After 2000, the summarized treatment outcomes were tending towards stability. In addition, geographic areas, type of the data and administrative level of the hospital were also found to influence the estimates of the treatment outcomes. Results of the present study clearly show, in general, that the pulmonary TB treatment achieved significant success in the past decade in the mainland of China. However, it needs to be further strengthened in the central and west areas.
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A modified chronic ocular hypertension rat model for retinal ganglion cell neuroprotection
Lichun Zhong
Front Med. 2013, 7 (3): 367-377.
https://doi.org/10.1007/s11684-013-0266-2
This study aimed to modify a chronic ocular hypertension (OHT) rat model to screen for potential compounds to protect retinal ganglion cells (RGCs) from responding to increased intraocular pressure (IOP). A total of 266 rats were prepared and randomly grouped according to different time-points, namely, weeks 3, 8, 16, and 24. Rats were sedated and eye examination was performed to score as the corneal damage on a scale of 1 to 4. The OHT rat model was created via the injection of a hypertonic saline solution into the episcleral veins once weekly for two weeks. OHT was identified when the IOP at week 0 was≥6 mmHg than that at week -2 for the same eye. Viable RGCs were labeled by injecting 4% FluoroGold. Rats were sacrificed, and the eyes were enucleated and fixed. The fixed retinas were dissected to prepare flat whole-mounts. The viable RGCs were visualized and imaged. The IOP (meanβ±βSD) was calculated, and data were analyzed by the paired t-test and one-way ANOVA. The OHT model was created in 234 of 266 rats (87.97%), whereas 32 rats (12.03%) were removed from the study because of the absence of IOP elevation (11.28%) and/or corneal damage scores over 4 (0.75%). IOP was elevated by as much as 81.35% for 24 weeks. The average IOP was (16.68β±β0.98)βmmHg in non-OHT eyes (n = 234), but was (27.95±0.97)βmmHg in OHT eyes (n = 234). Viable RGCs in the OHT eyes were significantly decreased in a time-dependent manner by 29.41%, 38.24%, 55.32%, and 59.30% at weeks 3, 8, 16, and 24, respectively, as compared to viable RGCs in the non-OHT eyes (P<β0.05). The OHT model was successfully created in 88% of the rats. The IOP in the OHT eyes was elevated by approximately 81% for 24 weeks. The number of viable RGCs was decreased by 59% of the rats in a time-dependent manner. The modified OHT model may provide an effective and reliable method for screening drugs to protect RGCs from glaucoma.
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Epidemiological study of a von Hippel-Lindau family in northwest China
Jingyao Zhang, Dapeng Wu, Hong Ai, Jigang Bai, Shunbin Dong, Qinling Yang, Kai Qu, Lei Zhou, Xinsen Xu, Chang Liu
Front Med. 2013, 7 (3): 378-385.
https://doi.org/10.1007/s11684-013-0276-0
von Hippel-Lindau (VHL) disease is a rare, inherited neoplastic disease characterized by hemangioblastomas (HBL) of the central nervous system (CNS), retinal angiomas, renal cell carcinomas (RCC), pancreatic endocrine tumors (PETs), pheochromocytomas, paragangliomas, and visceral cysts. We encountered a large VHL family in northwest China and conducted a systematic screening of the family members based on their epidemiological and clinical characteristics. A self-designed questionnaire was used to collect the general sociodemographic and health information of the family members. For the preliminary family screening, physical examination and abdomen B ultrasonography were performed. The suspected patients were subjected to cranial computerized tomography and fundus examination. The clinical data of the patients with confirmed VHL disease were collected from hospital records. A total of 63 lineal descendants in six generations were observed in the family (generations O, A, B, C, D, E), including 9 dead suspected cases (6 males, 3 females) and 10 living cases (2 males, 8 females). Among the 10 living cases, 4, 2, 1, 3, 4, 8, and 2 manifested HBLs of the CNS, PETs, RCC, pancreatic cysts, renal cysts, pheochromocytomas (4 hemi and 4 bilateral), and paragangliomas, respectively. Data showed that the morbidity of VHL disease in generation C was lower than that in generation B, but the age of onset was younger. This study is the first to report VHL disease in northwest China and VHL-associated PET cases in Chinese. Therefore, follow-up checkups of the family should be focused on younger generations. Proper family screening protocols should be followed for the treatment of patients with VHL disease.
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Cultural differences define diagnosis and genomic medicine practice: implications for undiagnosed diseases program in China
Xiaohong Duan, Thomas Markello, David Adams, Camilo Toro, Cynthia Tifft, William A. Gahl, Cornelius F. Boerkoel
Front Med. 2013, 7 (3): 389-394.
https://doi.org/10.1007/s11684-013-0281-3
Despite the current acceleration and increasing leadership of Chinese genetics research, genetics and its clinical application have largely been imported to China from the Occident. Neither genetics nor the scientific reductionism underpinning its clinical application is integral to the traditional Chinese worldview. Given that disease concepts and their incumbent diagnoses are historically derived and culturally meaningful, we hypothesize that the cultural expectations of genetic diagnoses and medical genetics practice differ between the Occident and China. Specifically, we suggest that an undiagnosed diseases program in China will differ from the recently established Undiagnosed Diseases Program at the United States National Institutes of Health; a culturally sensitive concept will integrate traditional Chinese understanding of disease with the scientific reductionism of Occidental medicine.
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