1.Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation
Tingting YANG ; Jiayu YUAN ; Yuting PENG ; Jiale PANG ; Zhen QIU ; Shangxiu CHEN ; Yuhan HUANG ; Zhenzhou JIANG ; Yilin FAN ; Junjie LIU ; Tao WANG ; Xueyan ZHOU ; Sitong QIAN ; Jinfang SONG ; Yi XU ; Qian LU ; Xiaoxing YIN
Journal of Pharmaceutical Analysis 2024;14(1):52-68
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
2.Angiomatoid fibrous histiocytoma:a clinicopathologic study of fourteen cases
Baofeng YANG ; Libing FU ; Nan ZHANG ; Xingfeng YAO ; Jiatong XU ; Xiaoxing GUAN ; Jianwen WANG ; Lejian HE
Chinese Journal of Clinical and Experimental Pathology 2024;40(8):818-823
Purpose To study the clinical and pathological features of angiomatoid fibrous histocytoma(AFH)and to ex-plore its diagnosis,differential diagnosis and prognosis.Meth-ods The clinicopathological and follow-up data were analyzed in 14 cases of AFH,and the literatures were reviewed.Results There were 11 males and 3 females.The age ranged from 11 months to 12 years and 11 months,with average 5.9 years.3 cases were located in limbs,and 5 cases in trunk,5 cases in head and neck region,and 1 of intracranial tumor.Histological-ly,14 cases were composed of fibrous capsules and lymphocyte sheaths,and cell nucleus were vacuolar,forming fascicles with focal whirling and synteny.Intralesional pseudoangiomatous spaces were noted in 9 cases.Calcification was found in 2 ca-ses.2 cases showed high mitotic acticity(11/10 HPF).Scle-rosing and/or myxoid stroma was seen in 3 cases.Tumors were immunopositive for desmin(10/14),EMA(12/14),CD99(12/14),SMA(9/12),ALK(7/8),and the average of Ki67 index was 16%.7 cases harbored EWSR1 rearrangenent(part-ner gene not identified),2 cases had EWSR1-ATF1 fusion and 2 EWSR1-CREB1 fusion.Clinical follow-up information was a-vailable for 14 cases(average 46 months).All the 14 cases were alive without recurrence and metastasis.Conclusion AFH is a borderline or low-grade malignant tumor,often demon-strates indolent behavior in children,but rarely recurs and me-tastasizes.The diagnosis and differential diagnosis require a comprehensive analysis of clinical features,histopathologic changes,immunohistochemical finding and EWSR1 or FUS gene detection results.
3.Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis
Jiatong XU ; Libing FU ; Xingfeng YAO ; Chao JIA ; Xiaoxing GUAN ; Meng ZHANG ; Lejian HE
Chinese Journal of Pathology 2024;53(4):344-350
Objective:To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma.Methods:Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children′s Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics.Results:Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease.Conclusions:Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.
4.Effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy
Xiaoxing LI ; Jiajun ZHANG ; Xinhui FAN ; Xintian SONG ; Feng XU ; Xiaoping JI ; Yuguo CHEN ; Chuanbao LI
Chinese Journal of Geriatrics 2023;42(9):1099-1104
Objective:To investigate the effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy and related mechanisms.Methods:Between January and December 2021, 60 6-week-old male C57BL/6J mice were chosen for the study, 40 were used to establish a diabetic cardiomyopathy model and the model was established in 28 mice, of whom, 14 were assigned to a non-intervention group and 14 to a dapagliflozin treatment group(intervention group).The rest of the 20 mice were in the control group.The mice in the intervention group were treated with dapagliflozin via oral gavage for 12 weeks.Cardiac structure and function were measured by ultrasound, the degree of myocardial fibrosis was evaluated by histology and electron microscopy, the concentrations of inflammatory factors were detected by enzyme-linked immunosorbent assays, apoptosis of myocardial cells was examined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL), and the level of myocardial oxidative stress was evaluated by dihydroethidium fluorescence.Results:At the end of the experiments, the body weight and fasting blood glucose in the intervention group were slightly lower than in the non-intervention group, but the difference was not statistically significant, while values from cardiac function parameters such as left ventricular ejection fraction were more favorable than in the non-intervention group[(61.07±4.66)% vs.(45.8±4.80)%, t=-5.24, P<0.05].Compared with the non-intervention group, the intervention group had alleviated myocardial hypertrophy, less myocardial disarray, and reduced collagen volume fraction[(18.4±1.9)% vs.(31.8±3.7)%, t=-12.0, P<0.05].Furthermore, the concentrations of inflammatory factors in the intervention group were lower than in the control group[interleukin-6: (82.19±10.90)ng/L vs.(291.02±31.02)ng/L, t=23.8, P<0.05; tumor necrosis factor-α: (70.45±12.13)ng/L vs.(201.31±27.10)ng/L( t=16.5), P<0.05; perforin 3: (13.05±2.04)μg/L vs.(42.40±1.26)μg/L( t=45.8), P<0.05; the index of myocardial apoptosis: 1.736±0.247 vs.0.864±0.129, t=11.7, P<0.05].The level of myocardial oxidative stress in the non-intervention group was higher than in the intervention group(2.655±0.252 vs.1.274±0.298, t=-13.3, P<0.05). Conclusions:Dapagliflozin can reduce myocardial hypertrophy and inhibit myocardial fibrosis through mitigating myocardial oxidative stress and inflammatory response, thus suppressing myocardial remodeling and ultimately protecting cardiac function in diabetic cardiomyopathy mice.
5. The value of the prominent hypointense vessels sign in acute ischemic stroke
Xiaoxing NI ; Shugang CAO ; Jian WANG ; Yuan FENG ; Wenan XU ; Mingwu XIA
Chinese Journal of Neurology 2020;53(1):64-71
Susceptibility-weighted imaging (SWI) is a tool that uses the intrinsic nature of local magnetic fields to enhance image contrast in order to improve the visibility of various susceptibility sources. SWI has blood oxygen levels dependent effect and is sensitive to the change of the cerebral oxygen saturation. This imaging method is applied to various diseases with abnormal deoxyhemoglobin concentration, such as ischemic stroke and cerebral arteriovenous malformation. Patients with acute ischemic stroke have elevated levels of deoxygenated hemoglobin in the affected area, so the ischemic area can show abnormal venous imaging on SWI images. SWI could recognize penumbra and guide the management of patients with acute stroke. Besides, SWI also could evaluate the severity of symptoms, predict prognosis and future surviving state. This paper reviews the research progress of the prominent hypointense vessels sign and its application in acute ischemic stroke.
6.Clinical-radiological-pathological Characteristics of 297 Cases of Surgical Pathology Confirmed Benign Pulmonary Lesions in Which Malignancy Could Not Be Excluded in Preoperative Assessment: A Retrospective Cohort Analysis in a Single Chinese Hospital.
Yongjian LIU ; Minjiang CHEN ; Chao GUO ; Wei ZHONG ; Qiuyue YE ; Jing ZHAO ; Qing ZHOU ; Xiaoxing GAO ; Xiaoyan LIU ; Hongge LIANG ; Yuequan SHI ; Delina JIANG ; Hongsheng LIU ; Yan XU ; Shanqing LI ; Mengzhao WANG
Chinese Journal of Lung Cancer 2020;23(9):792-799
BACKGROUND:
Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease.
METHODS:
From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted.
RESULTS:
297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%).
CONCLUSIONS
Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.
7.Correlation study of basilar artery dolichosis and clinical outcome of patients with acute isolated pontine infarction
Shugang CAO ; Qian WU ; Jun HE ; Xiaoxing NI ; Tingting GE ; Jian WANG ; Wen'an XU ; Mingwu XIA
International Journal of Cerebrovascular Diseases 2020;28(9):661-666
Objective:To investigate the correlation between basilar artery (BA) dolichosis and clinical outcome of patients with acute isolated pontine infarction.Methods:Consecutive patients with acute isolated pontine infarction within 7 d after onset admitted to the Department of Neurology, the Affiliated Hefei Hospital of Anhui Medical University were enrolled. The demographic, clinical and MRI data were collected. The modified Rankin Scale was used to evaluate the clinical outcome at 3 months after the onset. 0-2 was defined as good outcome, and >2 was defined as poor outcome. A binary multivariate logistic regression model was used to analyze the correlation between BA dolichosis and clinical outcome of the patients. Results:A total of 116 patients with acute isolated pontine infarction were enrolled. There were 69 (59.5%) males and 47 (40.5%) females, with a median age of 65 years (interquartile range: 57-76 years). There were 39 patients (33.6%) in BA dolichosis group and 77 (66.4%) in non-BA dolichosis group. The BA diameter ( P=0.021), theoretical length (basilar artery length, BAL) ( P<0.001), bending length (BL) ( P<0.001) and the proportion of patients with BA bending ( P<0.001) in the BA dolichosis group were significantly higher than those of the non-BA dolichosis group. There were 93 (80.2%) patients in good outcome group and 23 (19.8%) in poor outcome group. The baseline National Institute of Health stroke scale (NIHSS) score ( P<0.001), approximate length of BA ( P=0.007), BAL ( P=0.020), BL ( P=0.005) and the proportion of patients with BA dolichosis ( P=0.002) and bending ( P=0.008) in the poor outcome group were significantly higher than those in the good outcome group. Spearman correlation analysis showed that the approximate length of BA was significantly positively correlated with BL ( r=0.597, P<0001). Multivariate logistic regression analysis showed that BA dolichosis (odds ratio 5.441, 95% confidence interval 1.814-16.320; P=0.003) and the higher baseline NIHSS score (odds ratio 1.696, 95% confidence interval 1.291-2.228; P<0.001) were the independent risk factors for poor outcomes in patients with acute isolated pontine infarction. Conclusion:BA dolichosis is common in patients with acute isolated pontine infarction. BA dolichosis may be an independent risk factor for poor outcome in patients with acute isolated pontine infarction at 3 months after onset.
8. Preliminary study on the correlation between diversity of biliary flora and recurrence of common bile duct stones
Xiufang ZHA ; Shunfu XU ; Hong ZHU ; Xiaoxing CHEN ; Wenfang CHENG ; Bin XIAO ; Guosheng CHEN ; Jinliang NI
Chinese Journal of Digestion 2019;39(12):850-854
Objective:
To investigate the correlation between the diversity of biliary bacterial flora and the recurrence of common bile duct stones.
Methods:
From September 2018 to March 2019, 48 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) at the First Affiliated Hospital of Nanjing Medical University were enrolled and divided into primary choledocholithiasis (primary group, 38 patients) and recurrent choledocholithiasis group (recurrent group, 10 patients). The bile of the patients of the two groups was collected and analyzed with high-throughput sequencing of 16S rRNA. The Chao1 estimator indicated the richness of the biliary bacterial flora, and Shannon index and Simpson index demonstrated the diversity of biliary bacterial flora. The bacterial flora distribution was explored from different levels of phylum, class, order, family, genus and species. Chi-square test and
9.Recent advance in association between ring finger protein 213 gene p.R4810K and moyamoya disease
Xiaoxing NI ; Wen'an XU ; Mingwu XIA
Chinese Journal of Neuromedicine 2019;18(10):1054-1059
Moyamoya disease (MMD) is a chronic progressive steno-occlusive vasculopathy that involves terminal portions of the bilateral internal carotid arteries and/or the initial segment of the middle cerebral arteries and/or the initial segment of the anterior cerebral arteries. Ring finger protein 213 gene (RNF213) is considered as the major susceptibility gene of MMD.RNF213p.R4810K is mainly distributed in East Asians and is the founder variant of Asian patients with MMD.RNF213p.R4810K is associated with the incidence, prevalence, severity of illness and clinical manifestations of MMD. The biochemical mechanisms ofRNF213p.R4810K are still unclear and may affect angiogenesis of endothelial cells through both cell cycle-dependent and cell cycle-independent mechanisms. This paper reviews the research progress ofRNF213p.R4810K and the related mechanisms in MMD.
10.The perioperative bundle of care for advanced HCC patients receiving CT-guided percutaneous minimally-invasive argon-helium knife cryoablation
Tingye HU ; Xiufang XU ; Yuhe LU ; Kai WANG ; Gan ZHANG ; Lei XIA ; Jingsong ZHANG ; Xiaoxing ZHOU ; Shanshan ZHANG
Journal of Interventional Radiology 2018;27(1):80-82
Objective To discuss the clinical effect of perioperative bundle of care for patients with advanced hepatocellular carcinoma (HCC) who are receiving CT-guided percutaneous minimally-invasive argon-helium knife cryoablation.Methods A total of 30 HCC patients,who underwent percutaneous argonhelium knife cryoablation,were enrolled in this study.Perioperative measures based on the concept of bundle of care were implemented,which included training of nursing team members,perfect preoperative psychological nursing,dietary guidance,preoperative routine preparations,effective intraoperative guidance and close observation of the patient's condition,postoperative activity guidance,prevention and observation of complications,etc.Results All 30 advanced HCC patients could actively cooperate with physicians for the performance of percutaneous argon helium cryoablation.After the treatment,two patients developed nausea and vomiting and one patient developed chills and fever,which were improved after symptomatic treatment.All the 30 patients recovered well during the perioperative period and were discharged from hospital smoothly.Conclusion Perioperative bundle of care can help patients restore the surgical damage as soon as possible,reduce the pain and improve the quality of life.

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