1.Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy.
Xiaojun SONG ; Jianming LV ; Zhiqin CAO ; Huiyun HUANG ; Guodong CHEN ; Takayoshi AWAKAWA ; Dan HU ; Hao GAO ; Ikuro ABE ; Xinsheng YAO
Acta Pharmaceutica Sinica B 2021;11(6):1676-1685
Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P
2.Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity.
Zhiqin CAO ; Shaoyang LI ; Jianming LV ; Hao GAO ; Guodong CHEN ; Takayoshi AWAKAWA ; Ikuro ABE ; Xinsheng YAO ; Dan HU
Acta Pharmaceutica Sinica B 2019;9(2):433-442
Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.
3.A comparative study of the clinical features of thyrotropin-secreting pituitary adenomas
Xiaojing FAN ; Li ZANG ; Nan JIN ; Jin DU ; Lin WANG ; Weijun GU ; Kang CHEN ; Guoqing YANG ; Qinghua GUO ; Xianling WANG ; Zhaohui LV ; Jianming BA ; Jingtao DOU ; Yiming MU
Medical Journal of Chinese People's Liberation Army 2017;42(7):591-596
Objective To comparatively analyze the clinical characteristics of thyrotropin-secreting pituitary adenomas (TSH-omas).Methods The clinical features, laboratory variables, imaging and pathological Results were retrospectively compared and analyzed of 26 cases with TSH-omas admitted in Chinese PLA General Hospital from Feb. 2006 to Oct. 2016 and 20 cases with TSH-omas admitted in Shanghai Huashan Hospital from Apr. 2006 to Apr. 2013.Results The female ratio was slightly higher in patients of Chinese PLA General Hospital than in Huashan Hospital [(57.7%(15/26)vs. 45.0%(9/20)], while the mean age was similar [39.5±14.1(18-67 years)vs. 40.0±14.5(17-74 years)]. The most common chief complaint was thyrotoxicosis [73.1%(19/26)vs. 55.0%(11/20)], and mild-to-moderate goiter was the most common symptom. The mean serum TSH levels in Chinese PLA General Hospital and in Huashan Hospital were 5.06(2.97-6.27)mU/L and 6.16(3.76-10.91)mU/L respectively, and patients with normal serum TSH levels were more common in Chinese PLA General Hospital than in Huashan Hospital [57.7%(15/26)vs. 40.0%(8/20)]. Microadenoma was more common in Chinese PLA General Hospital than in Huashan Hospital [34.62%(9/26)vs. 20.0%(4/20)], while macroadenoma was more common in Huashan Hospital than in Chinese PLA General Hospital [20.0%(4/20)vs. 7.7%(2/26)]. Microadenoma was more common in female patients of the both groups [66.7%(6/9)vs. 75.0%(3/4)], while macroadenoma was all found in male patients. Tumor invasion of surrounding tissue and structure was often found in macroadenoma. In terms of octreotide inhibition test, the range of 24h TSH inhibition rate was roughly the same in the two groups (37.4%-91.8% and 46.5%-94.1%, respectively). Mixed adenoma was rare among all the pathologically confirmed cases. In Chinese PLA General Hospitals, TSH immunoreactive negative neoplastic cells were found in 3 of 8 cases, and octreotide scanning showed negative in 2 of 12 cases.Conclusions Patients with TSH-omas in the two hospitals show similarities but also some significant differences in the clinical features. Overall, the domestic patients with TSH-omas are diagnosed without gender difference according to the reports in China. The mean age at diagnosis is significantly younger than that in foreign data. Microadenoma is more common in females, while macroadenoma is more common in males. Serum TSH levels can be normal in patients with TSH-omas. Immunostaining and/or octreotide scanning for TSH can be negative.
4.A retrospective study on the clinical characteristics of patients with growth-hormone adenoma
Lu PENG ; Jingtao DOU ; Lele LI ; Li ZANG ; Nan JIN ; Yu PEI ; Weijun GU ; Jin DU ; Xianling WANG ; Guoqing YANG ; Jianming BA ; Zhaohui LV ; Juming LU ; Yiming MU
Medical Journal of Chinese People's Liberation Army 2017;42(7):597-602
Objective To evaluate the clinical characteristics of patients with growth-hormone adenoma (GHA) and summarize the diagnosis and treatment experience.Methods The clinical data of 338 GHA cases at the General Hospital of PLA from Jan. 1990 to Dec. 2016 were collected, of which 252 cases with more complete clinical data were retrospectively analyzed including their general situation, medical history, laboratory tests and auxiliary examinations, and treatment modalities and outcomes. Parts of the patients were followed up.Results The cases of hospitalized GHA patients have increased year by year since 1990, and the number of patients admitted in the last 3 years accounted for 56.2% of the total number of cases. The sex ratio for GHA patients was nearly 1:1. Age of visiting followed Gaussian distribution while the 41-50 age group occupied the largest part. The most typical sign is hand and foot enlargement (60.7%), followed by the hypertrophy of nasal ala. The most common symptoms are headache (42.5%), hypopsia, visual field defect and diplopia. More than half of GHA patients were complicated with prediabetes and diabetes (72.6%), sleep apnea (69.5%), goiter or thyroid nodularity (56.4%), cardiac insufficiency (57.0%) and colon polyp (54.1%); while the percentages of cases undergone the relevant examination in the total number of cases were as follows: 75g OGTT test (42.1%), polysomnography (23.4%), thyroid ultrasound (37.3%), echocardiogram (47.6%) and colonoscopy (14.7%); GHA was 23.37±1.42μg/L and IGF-1 was 804.28±273.93ng/ml on average; 85.0% of somatotroph tumors are macroadenoma. Surgery remains the mainstay of therapy to GHA, while medical therapy was selected by less patients. During the follow-up, only 38.0%of GHA patients can be contacted, among them the remission rate decreased to 40.5%. The positive rate of long-term remission evaluated by early postoperative GHA level was consistent with that confirmed by the long-term follow-up (χ2=3.368,P>0.05). Conclusions The number of hospitalized GHA patients have increased recent years. The common clinical signs and symptoms are somatic enlargement and nonspecific headache. Due to uncompleted screening, GHA associated complications are always misdiagnosed; It is essential to establish a sound model of follow-up to improve patients' quality of life. The early postoperative GHA levels may predict the prognosis of surgery.
5.Characteristics of brain functional alterations and task functional magnetic resonance imaging in patients with Cushing's disease
Dandan LIU ; Wei ZHOU ; Panlong LI ; Lele LI ; Wei CHEN ; Weijun GU ; Yu PEI ; Jin DU ; Li ZANG ; Nan JIN ; Lijuan YANG ; Jianming BA ; Zhaohui LV ; Yiming MU ; Baoci SHAN ; Lin MA ; Jingtao DOU
Medical Journal of Chinese People's Liberation Army 2017;42(7):583-590
Objective To analyze the relationship between the brain functional alterations of patients with Cushing's disease (CD) and patients' mental symptom by applying the Evaluating Emotional Scales and task functional magnetic resonance imaging (Task fMRI).Methods Task fMRI was performed on 8 patients with diagnosed CD admitted in the Department of Endocrinology of Chinese PLA General Hospital from Nov. 2015 to Nov. 2016 and 21 healthy people with matched age, gender and education level as control. Meanwhile, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Positive and Negative Affective Scale (PANAS) and Cushing Quality of Life Scale (Cushing QOL) were obtained to assess the brain functions.Results Significant depression and anxiety were observed in patients with CD, and their positive affective score was substantially lower while the negative affective score was relatively higher compared with that in the controls. Task fMRI revealed that, when watching the positive pictures, the activation degree of left cerebellum and right postcentral gyrus weakened in CD patients than in the controls, and the positive correlations existed between the activation degree of left cerebellum and the 16 o'clock adrenocorticotrophic hormone (ACTH) level, and between the activation degree of right postcentral gyrus and the urinary free cortisol (UFC) level in CD patients. In contrast, when watching the negative pictures, the activation degree of left cerebellum, bilateral parahippocampal gyrus and left inferior frontal gyrus was weakened in CD patients than in the controls, and the activation degree of left cerebellum was negatively correlated to the 0 o'clock cortisol level and SAS score, but is positively correlated to the UFC level. When watching the neutral pictures, the activation degree of left cerebellum and left parahippocampal gyrus was weakened in CD patients than in the controls.Conclusions CD patients may have impaired brain function with depression and anxiety mental symptoms. By Task fMRI, it can be found that the weakened activation degree of left inferior frontal gyrus, right postcentral gyrus, bilateral parahippocampal gyrus and left cerebellum may be related to CD patients' mental symptoms.
6.Effects of gender on screening value of aldosterone-renin ratio for primary aldosteronism
Yeqiong SONG ; Lin WANG ; Jie ZHU ; Xiaomeng JIA ; Ping PANG ; Nan JIN ; Li ZANG ; Guoqing YANG ; Weijun GU ; Jin DU ; Xianling WANG ; Qinghua GUO ; Lijuan YANG ; Zhaohui LV ; Jianming BA ; Jingtao DOU ; Yiming MU
Medical Journal of Chinese People's Liberation Army 2017;42(1):52-56
Objective To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR) for primary aldosteronism (PA).Methods The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH) patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC) was conducted to evaluate the best cut-off value.Results The plasma aldosterone concentration (PAC), serum sodium and ARR were much higher, but the plasma rennin activity (PRA), serum potassium and BMI were much lower in PA patients than in EH patients (P<0.01), and no significant difference existed between the two groups in age, duration of hypertension and blood pressure. The PRA was obviously lower in males than in females either in PA or in EH patients, but no signicantcant difference existed between males and females in PAC (P>0.05). The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC) was 0.968, the sensitivity and specicantcity was 92.44% and 93.08%, and the Youden index (YI) was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specicantcity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specicantcity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specicantcity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the ocantcial value recommended by guidelines.Conclusion Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher.
7.Diagnostic Value of Saline Load Test in Patients With Primary Aldosteronism
Lixue WANG ; Yiming MU ; Jianming BA ; Jingtao DOU ; Chaohui LV ; Xianling WANG ; Jin DU ; Gouqing YANG ; Juming LU
Chinese Circulation Journal 2016;31(6):604-605
Objective: To evaluate the diagnostic value of saline infusion test (SIT) in patients with primary aldosteronism (PHA). Methods: A total of 116 patients with PHA or essential hypertension (EH) treated in our hospital from 1994-06 to 2013-05 were retrospectively studied. The patients were divided into 2 groups: PHA group,n=72 and EH group, the patients with excluded PHA,n=44. post-SIT plasma levels of aldosterone and post-SIT ratio of aldosterone/renin activity were evaluated by ROC curve in order to analyze the diagnostic capability and the best diagnostic cut-off point. Results: The area under curve (AUC) by ROC for post-SIT aldosterone level was 0.759, the sensitivity and speciifcity were 74.6% and 63.6% respectively; AUC for post-SIT ratio of aldosterone/renin activity was 0.899, the sensitivity and speciifcity were 83.6% and 88.6% with the best diagnostic cut-off point at 111 [ng/dl:ng/(ml?h)]. Conclusion: Post-SIT plasma level of aldosterone and post-SIT ratio of aldosterone/renin activity had the diagnostic value of PHA; post-SIT ratio of aldosterone/renin activity had the higher diagnostic value of PHA.
9.Qualitative analysis on the utilization of health services and economic burden of the elderly pa-tients with diabetic foot ulcer
Hui LU ; Jianming WANG ; Jieqiong LV ; Ying WANG ; Jiqiang YUE ; Xinjuan SUN ; Aiping WANG
Chinese Journal of Health Policy 2015;8(3):60-64
Objective:To explore the health seeking behavior, utilization of health services and the economic burden of the elderly patients with diabetic foot ulcer ( DF) , with aim to provide policy evidence for improving their DF prevention and treatment outcomes. Methods: The purposive sampling method was applied to recruit 15 elderly DF patients treated in the 454 th Hospital of Chinese PLA from December 2013 to January 2014. After informed con-sent, they were in-depth interviewed. Results: The elderly with DF had a higher demand for the health services. They emphasized on treatment and neglected prevention. The utilization and efficiency of health services were affected by patients' economic level, medical insurance, capacity of community services, and so on. Conclusion:In order to improve the treatment outcome and quality of life for the elderly DF patients, it's necessary to strengthen patients' health education, to build a community-based and integrated health care system on DF prevention, treatment and management, and to develop the policies for reducing DF related economic burden.
10.Atypical 64 slice spiral CT imaging findings of pancreatic cancer
Tianshun MA ; Mingzhi LU ; Chengwei SHAO ; Changjing ZUO ; Jianping LU ; Taozhen LV ; Jianming ZHENG
Chinese Journal of Pancreatology 2010;10(3):174-176
Objective To analyze atypical 64-slice spiral CT imaging finings of pancreatic cancer and to improve the ability to identify CT manifestations of pancreatic cancer. Methods A retrospective analysis was performed on the atypical 64-slice spiral CT imaging findings of 12 eases of pancreatic cancer confirmed by pathology after surgery. Results All the twelve cases were pancreatic ductal adenocarcinoma.Among them, 7 cases were moderately differentiated ductal adenocarcinoma, 1 case was well-differentiated ductal adenocarcinoma, 1 case was mucinous adenocarcinoma, 3 cases were adenosquamous carcinoma. Among 8 cases with ductal adenocarcinoma, the lesions were located in the pancreatic head and (or) uncinate process in 7 cases, and in the pancreatic neck of 1 case. Tumors were expressed as isodense or low-density or cysticsolid lesions, the masses showed no enhancement in the enhanced scanning phase. Tumors were clearly exogenous or exogenous tendencies in 5 cases. Five cases had no distal pancreatic duct dilation, 2 patients had common bile duct and intrahepatic biliary dilation, and only 1 patient had atrophy of distal pancreas. There was one case of mucinous carcinoma, plain CT scan showed a cystic lesion in head of pancreas about 5cm in diameter, the solid part below the cystic lesion was slightly enhamced in the enhanced scanning phase and the body and tail pancreatic duct was moderately dilated (7 mm). There was no common bile duct and adjacent blood vessels invasion. Among 3 cases of adenosquamous carcinoma, lesions were located in the pancreatic head of 2 cases and in pancreatic body of 1 case. The maximal diameter of mass ranged 3.0 cm ~ 4.5 cm.Cystic necrotic area was observed within the lesions in 3 cases in enhanced pancreatic parenchymal phase of CT scan. Distal pancreatic duct were mildly dilated (4 ~ 5 mm) in 3 cases. There was no common bile duct and intrahepatic bile duct dilation. Conclusions Pancreatic cancer may show atypical CT imaging findings and great cautions are needed for differential diagnosis.

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