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.Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX)gene-transfected hepatic stellate cells
LIU HONGYI ; ZHOU YUANYUAN ; GUO PENG ; ZHENG XIONGWEI ; CHEN WEIBIN ; ZHANG SHICHAO ; FU YU ; ZHOU XU ; WAN ZHENG ; ZHAO BIN ; ZHAO YILIN
Journal of Zhejiang University. Science. B 2024;25(6):499-512
Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal failure.However,it has poor elasticity and compliance,leading to stenosis and thrombosis.The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial cells.Studies have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM fibers.Furthermore,mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure.Based on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV infection.Subsequently,these HBX-HSCs were implanted into a polycaprolactone-polyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold.We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization.Then,the vessel scaffold was implanted into a rabbit's neck arteriovenous fistula model.It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit's body.Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.
3.Resveratrol up regulates the expression of SIRT1 and mediates protective effect on radiation-induced myocardial injury
Yilin XU ; Yanxin CHEN ; Yini CAI ; Peng XU ; Zhimin ZENG ; Long HUANG ; Anwen LIU
Chinese Journal of Radiation Oncology 2023;32(5):457-463
Objective:To evaluate the effect of resveratrol on radiation-induced myocardial injury in mice.Methods:A total of 80 C57BL/6 mice were randomly divided into the control group, resveratrol (Res) group, radiation (RT) group and radiation+resveratrol (RT+Res) group. In the RT group, mice were given with heart radiation and mice in the Res group were given with resveratrol by gavage for 3 months. Cardiac ultrasound was used to evaluate cardiac function at 3 months after cardiac radiation. The hearts of mice were collected for HE staining, immunofluorescence, TUNEL staining, Masson staining and Western blot to evaluate the expression of silent information regulator 1 (SIRT1), the level of oxidative stress, inflammatory response, apoptosis and the degree of fibrosis in myocardial tissues. Experimental data were expressed as Mean ± SD. Continous data were statistically analyzed by t-test. Results:After 3 months of irradiation, compared with the control group, the ejection fraction (EF) and fractional shortening (FS) of cardiac function were decreased, and myocardial degeneration and disorder, reactive oxygen species (ROS) and inflammatory levels (interleukin-1β, interleukin-6, tumor necrosis factor-α), myocardial apoptosis (TUNEL positive cell rate) and fibrosis were increased in the RT group. In the RT+Res group, the cardiac function was improved, the expression of SIRT1 was increased, and the levels of oxidative stress, inflammation, myocardial apoptosis and fibrosis were decreased.Conclusions:Resveratrol can reduce oxidative stress, inflammatory infiltration, apoptosis and fibrosis of myocardium in mice with radiation-induced myocardial injury, thereby improving cardiac structural abnormalities and cardiac dysfunction. This protective effect can be mediated by upregulation of SIRT1 expression.
4.Research progress of predictive potential of the body mass index in fracture risk of children
Yilin YAN ; Peng HUANG ; Xinhong PEI
Chinese Journal of Applied Clinical Pediatrics 2022;37(7):558-560
The increasing prevalence of obesity in children worldwide has been a global healthy issue.It is important to identify the effect of fat mass on the bone, which contributes to promote the peak bone mass and prevent osteo-porosis-induced fracture.Body mass index (BMI), as an index to evaluate the state of obesity, is simple and easy to measure, and is suitable for self-test of a large range of people.This review aims to discuss the role of BMI in evaluating the interaction between obesity and bone density, and the predictive potential in fracture risk of children.
5. Genus Tetrastigma: A review of its folk uses, phytochemistry and pharmacology
Lizhi ZHANG ; Bin LI ; Mengyun WANG ; Haotian LIN ; Yilin PENG ; Xudong ZHOU ; Caiyun PENG ; Wei WANG ; Jixun ZHAN
Chinese Herbal Medicines 2022;14(2):210-233
The genus Tetrastigma belongs to the Vitaceae family and contains over 100 species. This paper reviewed folk uses, chemical constituents, pharmacological activities, and clinical applications of the medicinal plants in the genus Tetrastigma. In addition, the paper also discussed the current problems for the further studies. Up to now, more than 240 compounds were reported from the genus Tetrastigma, covering 74 flavonoids, 14 terpenoids, 19 steroids, 21 phenylpropanoids, 14 alkaloids and others constituents. Among them, flavonoids are the major and the characteristic chemical constituents in this genus. Modern pharmacological studies and clinical practice showed that the extracts and chemical constituents of Tetrastigma species possessed wide pharmacological activities including antitumor, antioxidative, hepatoprotective, antiviral, anti-inflammatory, and analgesic activities. The information summarized in this paper provides valuable clues for new drug discovery and an incentive to expand the research of genus Tetrastigma.
6.Genetic testing and prenatal diagnosis of two pedigrees affected with Huntington disease.
Yilin REN ; Peng DAI ; Chen CHEN ; Huikun DUAN ; Xiangdong KONG
Chinese Journal of Medical Genetics 2021;38(5):446-449
OBJECTIVE:
To explore the genetic basis for two Chinese pedigrees affected with Huntington disease and provide prenatal diagnosis for them.
METHODS:
Peripheral venous blood samples were collected from the probands. PCR and capillary gel electrophoresis were used to determine the number of CAG repeats in their IT15 gene. Pre-symptomatic testing was offered to their children and relatives, and prenatal diagnosis was provided to three pregnant women from the two pedigrees.
RESULTS:
The two probands, in addition with three asymptomatic members, were found to have a (CAG)n repeat number greater than 40. Upon prenatal diagnosis, the numbers of CAG repeats in two fetuses from pedigree 1 were determined as (16, 19) and (18, 19), both were within the normal range. A fetus from pedigree 2 was found to have a CAG repeat number of (15, 41), which exceeded the normal range.
CONCLUSION
Genetic testing can facilitate the diagnosis of Huntington disease and avoid further birth of affected children.
Child
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Female
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Genetic Testing
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Humans
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Huntington Disease/genetics*
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Nerve Tissue Proteins/genetics*
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Pedigree
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Pregnancy
;
Prenatal Diagnosis
7.MSCT analysis of integrity of Willis circle and the correlation with aneurysm
Yilin XIONG ; Changxiu PENG ; Yongshu LAN ; Guangyao FAN
Chinese Journal of Interventional Imaging and Therapy 2018;15(3):167-170
Objective To observe the relationship between the integrity of Willis circle and aneurysm with MSCT angiography.Methods CTA data of 580 patients with intracranial vascular lesions were retrospectively analyzed.The morphological structure of Willis circle and the occurrence of aneurysm were observed based on axial thin-layer,VR,MIP and MPR images.According to the integrity,Willis circle were divided into type Ⅰ (Willis circle complete),type Ⅱ (the anterior circulation complete but the posterior circulation incomplete),type Ⅲ (the anterior circulation incomplete but the posterior circulation complete) and type Ⅳ (both the anterior and posterior circulation incomplete) for statistical analysis.Results For the classification of Willis circle,there were 118 cases of type Ⅰ (118/580,20.34%),344 of type Ⅱ (344/580,59.31%),25 of type Ⅲ (25/580,4.31%) and 93 cases of type Ⅳ (93/580,16.03%).The incidence of Ⅰ-Ⅳtypes of Willis circle with aneurysm accounted for 16.10% (19/118),14.83% (51/344),32.00% (8/25) and 23.66% (22/93),respectively.The incidences of aneurysm in patients with different types of Willis circlewere statistically significant (x2=8.013,P=0.046).There was statistical difference of the type of Willis circle between different genders (x2=12.631,P=0.006),and the incidence of aneurysm in females was higher than that in males (25.00% [63/252] vs 11.28% [37/328];x2 =18.80,P<0.025).Conclusion Most Willis circle were not complete,and incomplete Willis circle aneurysm tended to occur in females with higher aneurysm rate.
8.The study of application of thrombus elastograph in evaluating coagulation function of patients with acute ischemic stroke
Li WEI ; Yilin YANG ; Ya PENG ; Peng ZHOU ; Chenhong QU
International Journal of Laboratory Medicine 2018;39(5):573-576
Objective To evaluate the role of thrombus elastograph (TEG) in evaluating the coagulation function of patients with acute ischemic stroke.Methods Totally 116 cases of patients with acute ischemic stroke and 116 cases of health physical examination people from our hospital were selected as case group and control group.The blood clotting index and thrombelastogram index of the groups were detected.Results In case group of acute phase,fibrinogen (FIB),two D-dimer (D-D),maximum blood clot strength (MA),0.5 h blood clot reduction rate of MA (LY30),alpha angle,integrated coagulation index (CI) and blood clot strength (G) were significantly higher than those of control group and the recovery period group.The difference was statistically significant(P<0.01).In cases of acute phase,activated partial thromboplastin time (APTT),prothrombin time (PT),PT-INR,reaction time (R),clot formation time (K value) were significantly lower than those in the healthy control group and the recovery period cases,the difference was statistically significant (P<0.01).MA,LY30,α Angle and CI were negatively correlated with PT,APTT,PT-INR,and were positively correlated with FIB,D-D(P<0.05);R value,K value were positively correlated with PT,APTT,PT-INR,and were negatively correlated with FIB,D-D(P< 0.05).Conclusion TEG plays a significant role in monitoring and evaluating coagulation function in patients with acute ischemic stroke,and has important evaluation effect on the prognosis of disease.It is worthy of clinical application.
9.Value of serum human epithelial growth factor receptor 2 extracellular domain and circulating tumor cells in evaluating therapeutic response in advanced gastric cancer.
Yilin LI ; Zhi PENG ; Xiaotian ZHANG ; Jifang GONG ; Lin SHEN
Chinese Journal of Gastrointestinal Surgery 2017;20(11):1293-1299
OBJECTIVETo examine the correlation between serum human epithelial growth factor receptor 2 extracellular domain (HER2 ECD) and circulating tumor cells (CTC), as well as the dynamic variation of HER2 ECD and its correlation to the therapeutic efficacy.
METHODSFifty-three advanced gastric cancer (AGC) patients who treated in Peking University Cancer Hospital and ever enrolled into CTC study (ClinicalTrial gov. ID: NCT01625702) were retrospectively included in this study.
INCLUSION CRITERIAthe patients were histologically confirmed as locally advanced or recurrent and/or metastatic adencarcinoma; they received two or more cycles of fluorouracil-based chemotherapy or combination targeted therapy; serum CTC was counted before and after therapy; the clinical response was evaluated every 2 cycles of treatment by the presence of at least one measurable lesion according to RECIST version 1.1 criteria. This study was approved by Ethics Committee of Peking University Cancer Hospital, and informed consents were signed by patients. The sera before and after two cycles of treatment were collected for CTC enumeration and HER2 ECD detection, in which the levels of HER2 ECD were measured by chemiluminescence immunoassays method. The positive threshold value of HER2 ECD and CTC number were ≥15 μg/L and ≥3 CTCs/7.5 ml respectively. The progression-free survival (PFS) and overall survival (OS) were compared among different groups using Log-rank tests.
RESULTSIn 53 enrolled patients, 39 were histologically identified as negative HER2, 9 as positive HER2 and another 5 cases were unknown. All the patients received fluorouracil-based chemotherapy, and 9 positive HER2 patients received combined anti-HER2 targeted therapy. Before therapy, the median HER2 ECD concentration of 53 cases was 10.45 (8.0 to 83.2) μg/L. Seven patients exhibited positive HER2 ECD levels, in whom 4 were histologically HER2 positive, but 3 were histologically HER2 negative. The median CTC number of 53 cases was 2 (0 to 668) CTCs/7.5 ml, and the positive rate of CTC was 47.2%(25/53). Following 2 cycles of therapy, a total of 10 histologically HER2 negative patients exhibited positive HER2 ECD levels, in whom 2 also possessed positive HER2 ECD levels, 83.3 μg/L and 46.9 μg/L before therapy, and 22.4 μg/L and 20.4 μg/L after therapy respectively, whereas another 8 patients (10.3 to 14.5 μg/L before therapy) acquired the elevated expression of HER2 ECD following therapy (15.1 to 19.5 μg/L). It seems that the increased level of HER2 ECD after therapy was, though not statistically significant, correlated to low number of CTCs. In histologically HER2 negative patients, pretherapeutic HER2 ECD level (positive vs. negative) was not significantly correlated to PFS (7.6 months vs. 4.4 months, P=0.328) and OS (13.6 months vs. 10.9 months, P=0.679). However, in histologically HER2 positive patients, patients with positive HER2 ECD level before therapy exhibited longer PFS (10.7 months vs. 4.2 months, P=0.025) and OS (16.5 months vs. 8.9 months, P=0.015) compared to those with negative HER2 ECD level. Additionally, CTC number was significantly correlated to prognosis in histologically HER2 negative patients. Patients with positive pretherapeutic CTC number showed longer PFS (5.3 months vs. 3.3 months, P=0.049) and OS (14.3 months vs. 7.6 months, P=0.001) as well. While in histologically HER2 positive patients, CTC number was not obviously correlated to the PFS and OS. In above 8 negative HER2 patients acquiring elevated expression of HER2 ECD following therapy, the increased HER2 ECD level was not correlated to PFS and OS (all P>0.05). In 9 histologically HER2 positive patients, 4 patients who exhibited decreased HER2 ECD level and reduced or constant CTC number had longer PFS (7.5 to 15.3 months) and OS (11.0 to 26.3 months) compared with those 2 patients who suffered from acquired HER2 ECD level following therapy (PFS 3.0 to 4.8 months and OS 7.3 to 8.6 months).
CONCLUSIONSIn histologically HER2 positive patients, increased pretherapeutic HER2 ECD level predicts better prognosis. The acquired elevated HER2 ECD level following therapy is correlated to inefficient therapeutic response. The acquirement of elevated HER2 ECD level can also be found in histologically HER2 negative patients, which may be correlated to the corresponding variation of CTC number.
10.Combined use of the Solitaire stent and Neuro 053 delivery catheter for mechanical thrombectory of acute intracranial vessel occlusion
Ya PENG ; Jinggang XUAN ; Ronghua CHEN ; Xucheng ZHU ; Huaming SHAO ; Jie CAO ; Yilin YANG
Chinese Journal of Cerebrovascular Diseases 2015;(3):144-147
Objective To investigate the preliminary experience of mechanical thrombectomy with a tri-axial system of the Solitaire AB stent through a Neuro delivery catheter to treat intracranial large artery occlusion. Methods A tri-axial system was used to deliver the Solitaire AB stent through a Neuro delivery catheter to provide intracranial aspiration in close proximity to the stent. This technique was used in 1 case of acute middle cerebral artery occlusion and 1 case of acute basilar artery occlusion. Results Successful revascularization was achieved in these 2 cases. Thrombolysis in cerebral infarction (TICI)score was 3. The clot length of acute middle cerebral artery occlusion was 3 cm and the modified Rankin Scale (mRS)score of this case was 3 at 90 days follow-up. Another patient with acute bilateral vertebral occlusion was revealed successful recanalization by angiography. Conclusion The results suggest that this technique of a tri-axial system used of the Solitaire stent through a Neuro delivery catheter can effectively retrieve clots from the occlusive artery and minimize the chance of antegrade blood flow dislodging the thrombus.

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