1.LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells.
Zhen SUN ; Hua YU ; Jing ZHAO ; Tianyu TAN ; Hongru PAN ; Yuqing ZHU ; Lang CHEN ; Cheng ZHANG ; Li ZHANG ; Anhua LEI ; Yuyan XU ; Xianju BI ; Xin HUANG ; Bo GAO ; Longfei WANG ; Cristina CORREIA ; Ming CHEN ; Qiming SUN ; Yu FENG ; Li SHEN ; Hao WU ; Jianlong WANG ; Xiaohua SHEN ; George Q DALEY ; Hu LI ; Jin ZHANG
Protein & Cell 2022;13(7):490-512
		                        		
		                        			
		                        			LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			Cell Differentiation
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		                        			Embryo, Mammalian/metabolism*
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		                        			Embryonic Development
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		                        			Mice
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		                        			Pluripotent Stem Cells/metabolism*
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		                        			RNA, Messenger/genetics*
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		                        			RNA, Ribosomal
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		                        			RNA-Binding Proteins/metabolism*
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		                        			Transcription Factors/metabolism*
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		                        			Zygote/metabolism*
		                        			
		                        		
		                        	
2.Survival analysis of HIV-infected patients on antiretroviral therapy during 2006-2019 in Taizhou City
Xiao-qin LI ; Jia-yu HE ; Shan-ling WANG ; Yuan-yuan XU ; Wei-wei SHEN ; Ying-ying DING ; Na HE ; Xiao-xiao CHEN
Shanghai Journal of Preventive Medicine 2021;33(9):779-784
		                        		
		                        			
		                        			Objective:To examine the survival status and explore factors related to death among human immunodeficiency virus (HIV) infected patients receiving antiretroviral therapy (ART) in Taizhou City during 2006‒2019. Methods:A retrospective cohort study was conducted to analyze the data on HIV-infected patients receiving ART in Taizhou during 2006‒2019. Kaplan-Meier (K-M) method was used to calculate the cumulative survival rate and cumulative treatment success rate. Cox regression model was used to determine survival status and factors associated with ART. Results:A total of 2 904 HIV-infected patients was included. The cumulative survival rate after 1, 3, 5, and 8 years of ART were 96.9%, 94.9%, 93.1% and 92.1%, respectively, and the cumulative treatment response rate were 91.3%, 85.3%, 81.8% and 73.8%, respectively. Compared with aged 18-30 years old, baseline CD4+T cell >350 count/μL, normal hemoglobin level, effective ART, no clinical symptom at baseline, and homosexual transmission, we found that aged 51-60 years old(
		                        		
		                        	
3.The effects of low-frequency transcranial magnetic stimulation combined with hyperbaric oxygen in the treat-ment of non-fluent aphasia
Yi ZHANG ; Wenwei YUN ; Min ZHANG ; Yun CHEN ; Yin CAO ; Xianju ZHOU
Chinese Journal of Physical Medicine and Rehabilitation 2019;41(7):512-516
		                        		
		                        			
		                        			Objective To investigate the effect of repeated application of low-frequency transcranial magne-tic stimulation ( rTMS) when combined with hyperbaric oxygen ( HBO) in the treatment non-fluent aphasia after a stroke. Methods Forty-eight stroke survivors with non-fluent aphasia were randomly assigned to a control group, an HBO group or an observation group, each of 16. All received conventional rehabilitation therapy consisting of drug therapy, speech training and conventional physical exercises, while the HBO and observation groups were additionally given HBO and rTMS combined with HBO respectively. The 1 Hz rTMS was applied over the Broca's homologues of the unaffected hemisphere. Before and after 4 weeks of treatment, the Western Aphasia Battery ( WAB) was used to evaluate the subjects' language function and the Modified Barthel Index ( MBI) was used to assess their ability in the activities of daily living. Results There was no significant difference in the average WAB scores among the three groups before the treatment. After 4 weeks of treatment the average WAB and MBI scores of the HBO group and the observation group had improved significantly, and there was then a significant difference among the three groups. The observation group was performing significantly better than the HBO group and the control group in spontaneous speech, auditory comprehension, repetition, naming, AQ score and MBI score. Pairwise comparisons showed that the observation group's average WAB score, spontaneous speech, auditory comprehension, repetition, naming, AQ score and MBI score were the best, followed by those of the HBO group and then those of the control group. All of the differences were statistically significant. Conclusions Low-frequency rTMS combined with HBO can significantly improve the language function and the quality of life of patients with non-fluent aphasia. Such combined therapy is worthy of clinical promotion and application.
		                        		
		                        		
		                        		
		                        	
4.Influence of estimated glomerular filtration rate in motor function rehabilitation and short-term prognoses in patients with acute middle cerebral artery infarction
Yi ZHANG ; Min ZHANG ; Wenwei YUN ; Yin CAO ; Yuan CHEN ; Zhixiang ZHANG ; Yu TAO ; Jingjing WANG ; XianJu ZHOU
Chinese Journal of Neuromedicine 2019;18(11):1109-1115
		                        		
		                        			
		                        			Objective To investigate the influence of estimated glomerular filtration rate (eGFR) in rehabilitation of motor function and short-term prognoses in patients with acute middle cerebral artery (MCA) infarction. MethodsSeventy-four patients with acute MCA infarction, admitted to Department of Neurology from March 2016 to September 2018, and then, accepted rehabilitation training for 4 weeks in Department of Rehabilitation medicine, were recruited. Modification of Diet in Renal Disease was used to evaluate the eGFR instead of renal function; according to the results, these patients were divided into normal renal function group and mild-moderate renal dysfunction group. National Institute of Health Stroke Scale (NIHSS) was used to assess the neurologic function. Fazekas scale was used to assess degrees of leukoaraiosis. Fugl-Meyer Motor Function Assessment (FMA) was used to assess motor functions before rehabilitation treatment and 90 d after onset. Modified Barthel Index (MBI) was used to assess activity of daily living 90 d after onset. According to MBI scores, the patients were divided into good prognosis group (MBI scores>60) and poor prognosis group (MBI scores≤60); multivariate Logistic regression analysis was used to confirm the risk factors affecting prognoses 90 d after onset.ResultsAmong 74 enrolled patients, 40 were classified as normal renal function group and 34 as mild-moderate renal dysfunction group; patients in the mild-moderate renal dysfunction group had significantly higher level of blood urea nitrogen, proportion of silent lacunar cerebral infarction and Fazekas scale scores, and had statistically lower FMA scores and MBI 90 d after onset than normal renal function group (P<0.05). Among the 74 patients, good prognosis was found in 32 patients and poor prognosis in 42 patients; multivariate Logistic regression analysis found that age, eGFR (OR=0.944,P= 0.011, 95%CI: 0.903-0.987), baseline NIHSS scores, and Fazekas scale scores were risk factors affecting prognoses 90 d after onset.ConclusionIn acute MCA infarction patients, eGFR can influence the rehabilitation of motor function and short-term prognoses.
		                        		
		                        		
		                        		
		                        	
5. Clinical value of health-related quality of life evaluation in community patients with hepatitis B
Ping CHEN ; Jiawei ZHU ; Ting CHEN ; Danfeng WANG ; Liping YANG ; Bing RUAN ; Chengbo YU ; Lanjuan LI
Chinese Journal of Hepatology 2017;25(4):313-316
		                        		
		                        			
		                        			 Chronic hepatitis B (CHB) is a major infectious disease which threatens people’s health around the world. Health-related quality of life (HRQoL) has become an important index for evaluating the treatment and prognosis of patients with CHB. Many studies abroad have shown that the HRQoL of patients with CHB is influenced by various factors. Disease severity, clinical symptoms, and low self-efficacy are important influencing factors for patients’ quality of life. Anti-viral therapy, proper physical therapy, or psychological intervention can significantly improve the HRQoL of community CHB patients, and HRQoL is even significantly improved in patients undergoing liver transplantation one year ago. These studies provide valid evidence for antiviral therapy for hepatitis B patients and liver transplantation techniques from the psychological level. At present, there still lacks studies on HRQoL of CHB patients in China. This article summarizes the measurement tools for HRQoL widely used in recent years in China and foreign countries, reviews the research advances in HRQoL in community patients with CHB, and discusses the perspectives for future studies. 
		                        		
		                        		
		                        		
		                        	
6.Activation of Rip1 promotes necroptosis in LNCaP-AI cells via inhibiting SHARPIN
Ganping WANG ; Hai HUANG ; Xianju CHEN ; Yiming LAI ; Chunhao LIN ; Lexiang ZENG ; Yi CAO ; Yiming ZHANG ; Yongsheng YU ; Zhenghui GUO
Chinese Journal of Pathophysiology 2016;32(7):1214-1220
		                        		
		                        			
		                        			[ ABSTRACT] AIM:To explore the role of SHARPIN in regulation of Rip1 in castration-resistant prostate cancer LNCaP-AI cells.METHODS:The LNCaP-AI cells were treated with TNF-α+Z-VAD ( an inhibitor of pan-caspase) to activate necroptosis, which were compared to the cells treated with TNF-α+Z-VAD+Nec-1 ( an inhibitor of Rip1 ) .A blank group and a TNF-α-treated group were set up as controls.The cell viability in each group was measured by MTS as-say.In addition, SHARPIN was knocked down by siRNA, and the inhibitory efficiency was evaluated by RT-qPCR.The expression of Rip1 at mRNA and protein levels after knocking down SHARPIN was determined by RT-qPCR and Western blot to explore the underlying mechanism of regulatory network of necroptosis in prostate cancer.RESULTS: Compared with blank control group and TNF-α-treated group, the viability of LNCaP-AI cells treated with TNF-α+Z-VAD decreased by 28%(P<0.05).After treated with TNF-α+Z-VAD+Nec-1, the LNCaP-AI cells showed no significant difference in the viability compared with blank control and TNF-α-treated groups.Taken together, necroptosis may be an important way of cell death in LNCaP-AI cells.Besides, the expression of Rip1 at protein level was up-regulated following the inhibition of SHARPIN using siRNA, indicating that down-regulation of SHARPIN enhanced necroptosis via activating Rip1 in 
 LNCaP-AI cells.CONCLUSION:Necroptosis is an important way of cell death .Inhibition of oncogenic factor SHARPIN enhances necroptosis via activating Rip1 in LNCaP-AI cells.
		                        		
		                        		
		                        		
		                        	
7.Hematologic toxicity of Gynura segetum and effects on vascular endothelium in a rat model of hepatic veno-occlusive disease.
Junwei FANG ; Guohua ZHANG ; Xianmu TENG ; Zhiqin ZHANG ; Jinhui PAN ; Qiyang SHOU ; Minli CHEN
Chinese Journal of Hepatology 2015;23(1):59-63
OBJECTIVETo observe the effects ofGynura segetum in rats with hepatic veno-occlusive disease (HVOD).
METHODSSixty Sprague-Dawley rats were assigned to a blank control group, one of three Gynura segetum treatment groups (low-dose group, 5.0 g/kg; mid-dose group, 10 g/kg; high-dose group, 20 g/kg), or a pseudo-drug group (10 g/kg of pseudo-ginseng). After 28 days of treatment, effects on white blood cell count, coagulation, secreted factors from vascular endothelium, and histopathology of the spleen were observed and inter-group differences were statistically assessed.
RESULTSAfter the 4-week administration, all rats in the Gynura segetum treatment groups showed decrease in body weight, increases in numbers of leukocytes, neutrophils, lymphocytes, monocytes and eosinophils.decreases in platelets and platelet hematocrit, and increases in mean platelet volume and platelet distribution.In addition, the Gynura segetum treatments increased the prothrombin time, activated partial thromboplastin time, thrombin time, prothrombin ratio and international normalized ratio, but decreased the PT%, fibrinogen level and platelet aggregation.Serum levels of endothelin and nitric oxide were also elevated by the Gynura segetum treatments.All measured parameters showed significant differences from the control group (P less than 0.01 or less than 0.05).Finally, the splenic follicles were significantly reduced and the spleens showed an absence of germinal centers along with a large number of diffuse lymphocytes and reduced red pulp sinusoids.
CONCLUSIONThe Gynura segetum treatment has some toxic effects; it can reduce platelet count and platelet hematocrit, inhibit blood clotting time and platelet aggregation, increase the secretion of factors from the vascular endothelium and disrupt spleen histology.
Animals ; Asteraceae ; Blood Coagulation ; Blood Platelets ; Disease Models, Animal ; Endothelium, Vascular ; Hepatic Veno-Occlusive Disease ; Platelet Count ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley
8.Knockdown of SALL4 expression regulates cell proliferation and apoptosis in prostate cancer LNCaP cells
Jin LI ; Hai HUANG ; Yiming LAI ; Lexiang ZENG ; Yi CAO ; Ganping WANG ; Xianju CHEN ; Yongsheng YU ; Jieqing CHEN ; Simin ZHANG ; Yiming ZHANG ; Zhenghui GUO
Chinese Journal of Pathophysiology 2015;(3):435-439
		                        		
		                        			
		                        			[ ABSTRACT] AIM: To investigate the SALL4 expression, proliferation and apoptosis in the LNCaP cells after transfection of SALL4 siRNA.METHODS: The expression of SALL4 at mRNA and protein levels was detected by real-time PCR and Western blotting.MTS assay, colony formation assay and flow cytometry were used to determine the prolifer-ation, colony formation ability and apoptosis of the LNCaP cells.The effect of SALL4 on the expression of Bax and Bcl-2 was analyzed by Western blotting.RESULTS:Compared with negative control group, the expression of SALL4 at mRNA and protein levels in LNCaP cells was down-regulated by transfection of SALL4 siRNA ( P<0.05 ) .The proliferation rate and colony formation ability were decreased, while apoptosis rate increased in si-SALL4 group (P<0.05).Higher expres-sion of Bax and lower expression of Bcl-2 in si-SALL4 group were observed ( P<0.05 ) .CONCLUSION:Down-regula-tion of SALL4 by siRNA not only suppresses LNCaP cell proliferation and colony formation, but also inhibits Bcl-2 expres-sion and activates Bax expression to induce apoptosis.
		                        		
		                        		
		                        		
		                        	
9.The efficacy of fascia iliaca compartment block combined with general anesthesia for total hip arthroplasty
Chinese Journal of Postgraduates of Medicine 2015;38(8):551-554
		                        		
		                        			
		                        			Objective To investigate the efficacy of fascia iliaca compartment block combined with general anesthesia for total hip arthroplasty.Methods Fifty patients underwent total hip arthroplasty were divided into trial group or control group by random digits table method with 25 cases each.Preoperatively,both groups were given fascia iliaca compartment block with the trial group receiving 60 ml 0.25% ropivacaine and the control group receiving 60 ml 0.9% sodium chloride.Both groups received general anesthesia.The consumption of general anesthetics and intraoperative hemodynamic variation in the 2 groups were recorded.The recovery time,extubation time,observer's assessment of alertness/sedation score (modified OAA/S) at 15 and 30 min postoperative and visual analog score (VAS) at postoperative instantly were compared between the 2 groups.Results The consumptions of propofol and remifentanil during maintenance of anesthesia in trial group were significantly lower than those in control group,and there were statistical differences:(250 ± 40) mg vs.(420 ± 85) mg and (300 ± 50) μ g vs.(600 ± 150) μ g,P < 0.01.The recovery time and extubation time in trial group were significantly shorter than those in control group,and there were statistical differences:(7.2 ± 4.5) min vs.(16.2 ± 7.1) min and (8.0 ± 2.8) min vs.(20.0 ± 8.3) min,P < 0.01.The modified OAA/S at 15 and 30 min postoperative in trial group were significantly higher than those in control group,and there were statistical differences:(4.3 ± 0.3) scores vs.(3.0 ± 1.2) scores and (4.6 ± 0.2) scores vs.(3.9 ± 0.8) scores,P < 0.01.The VAS at postopcrative instantly in trial group was significantly lower than that in control group,there was statistical difference:(1.6 ± 0.9) scores vs.(4.5 ± 0.8)scores,P < 0.01.The degree of satisfaction in trial group was better than that in control group,and there was statistical difference (P < 0.05).Conclusion Compared with general anesthesia alone for total hip arthroplasty,the fascia iliaca compartment combined with general anesthesia has better hemodynamic stability,marked reduction of consumption of general anesthetics,rapid recovery and good postoperative analgesia.
		                        		
		                        		
		                        		
		                        	
10.Epidemiological analysis on 589 children with hand-foot-mouth disease from Xianju county of Zhejiang province.
Jianying WANG ; Huoming ZHU ; Yaqin CHEN ; Yijian ZHANG
Chinese Journal of Epidemiology 2014;35(6):708-709
OBJECTIVETo investigate the epidemiological characteristics of hand-foot-mouth disease.
METHODSA total of 589 children from Xianju county, Zhejiang province with hand-foot-mouth disease in 2013 were recruited in the study and the diagnosis went through clinical and laboratory confirmation. Attributes that were analyzed included gender, age, month of occurrence, regional distribution and clinical presentation.
RESULTSThe incidence rate of hand-foot-mouth disease in Xianju county for the year was 102.72/100 000, with 12 severe cases but no death. There were clearly more boys than girls, with a male to female ratio of 1.29 :1, which was statistically significant (χ(2) = 14.274, P < 0.001). The vast majority of patients were 0-3 years old, representing 94.74% of the patients. The occurrences were concentrated in the period from April to August and November, with April as the high-incidence season. High incidence areas were the countryside and suburbs, making up 45.50% and 30.73%, respectively, of all cases. Most patients were in preschools or scattered home care environments, accounting for 51.10% and 40.92% , respectively. Clinical presentation was characterized by fever and various kinds of vesicles or papules at the hand, foot, mouth or buttocks.
CONCLUSIONMost of hand-foot-mouth disease cases occur in younger children in areas with inadequate knowledge of hygiene, with seasonal variation.
Child ; Child, Preschool ; China ; epidemiology ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; Humans ; Infant ; Male
            
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