Cardiotrophin-1 promotes cardiomyocyte differentiation from mouse induced pluripotent stem cells via JAK2/STAT3/Pim-1 signaling pathway

Background The induced pluripotent stem cell （iPSC） has shown great potential in cellular therapy of myocardial infarction （MI）, while its application is hampered by the low efficiency of cardiomyocyte differentiation. The present study was designed to investigate the effects of cardiotrophin-1 （CT-1） on cardiomyocyte differentiation from mouse induced pluripotent stem cells （miPSCs） and the underlying mechanisms involved. Methods The optimal treatment condition for cardiomyocyte differentiation from miPSCs was established with ideal concentration （10 ng/mL） and duration （from day 3 to day 14） of CT-1 administration. Up-regulated expression of cardiac specific genes that accounted for embryonic cardiogenesis was observed by quantitative RT-PCR. Elevated amount of a-myosin heavy chain （ct-MHC） and cardiac troponin I （cTn I） positive cells were detected by immunofluorescence staining and flow cytometry analysis in CT- 1 group. Results Transmission electron microscopic analysis revealed that cells treated with CT- 1 showed better organized sacromeric structure and more mitochondria, which are morphological characteristic of matured cardiomyocytes. Western blot demonstrated that CT-1 promotes cardiomyocyte differentiation from miPSCs partly via JAK2/STAT3/Pim-1 pathway as compared with control group. Conclusions These findings suggested that CT-1 could enhance the cardiomyocyte differentiation as well as the maturation of mouse induced pluripotent stem cell derived cardiomyocytes by regulating JAK2/STAT3/Pim-1 signaling pathway.

Comparison of scleral buckling using wide-angle viewing systems and indirect ophthalmoscope for rhegmatogenous retinal detachment

AIM：To compare the effects of scleral buckling using wide-angle viewing systems（WAVS） with that using indirect ophthalmoscope for the treatment of rhegmatogenous retinal detachment.METHODS：The study was a retrospective analyses of the medical records of 94 eyes（94 patients） with rhegmatogenous retinal detachment.Among them,47 eyes underwent scleral buckling using WAVS with endoiiluminator（Group W）,and 47 eyes underwent scleral buckling using indirect ophthalmoscope（Group I）.Surgical durations,primary success rate,best-corrected visual acuities（BCVA）,delayed subretinal fluid absorptions and surgical complications were compared between the two groups.RESULTS：At baseline,there were no statistical differences between the two groups in patient＇s age（P=0.997）,gender（P=0.853）,symptom duration（P=0.216）,BCVA（P=0.389）,refractive error（P=0.167）,intraocular pressure（P=0.595）,the number of retinal breaks（P=0.832）,the extent of retinal detachment（P =0.246）,subretinal demarcation line（P=0.801）,and macular detachment（P=0.811）.The follow-up period was 12 mo.The surgical durations in Group W（with or without encircling buckling） were significant shorter than those in Group I（P〈0.001 respectively）.The primary success rate was94.27%in Group W,which was similar to that in Group I（92.38%,P=0.931）.The BCVA in Group W was better than that in Group I（P〈0.001） at 1-month follow-up visit.However,there were no significant differences between the two groups at 3-month（P=0.221）,6-month（P =0.674）,and 12-month（P=0.363） follow-up visits respectively.Delayed subretinal fluid absorptions were more common in Group I than in Group W at 1-month（P=0.045） follow-up visit,but there were no significant differences between the two groups at 3-month（P=0.111）,6-month（P =1.000） and 12-month follow-up visits respectively.CONCLUSION：Scleral buckling using WAVS can be an alternative choose for rhegmatogenous retinal detachment

Efficacy and safety of subthreshold micropulse laser in the treatment of acute central serous chorioretinopathy

·AIM:To analyze the efficacy and safety of subthreshold micropulse laser(SML)in the treatment of acute central serous chorioretinopathy(CSC).·METHODS:This is a retrospective case analysis study.Totally 58 eyes of 58 patients were enrolled,and they were divided into different groups.And 39 patients were treated with SML(SML group)and 19 patients were only observed(observation group).The follow-up period was 3mo after diagnosis.The best corrected visual acuity(BCVA),central retinal thickness(CRT),superficial retinal vascular density(SRVD),deep retinal vascular density(DRVD),the superficial and deep foveal avascular zone(FAZ)area,retinal light sensitivity(RLS),perfusion area of choroidal capillary layer(CCL),subfoveal choroidal thickness(SFCT)and fundus autofluorescence(FAF)were investigated.·RESULTS:The BCVA,CRT,SRVD,DRVD,the superficial and deep FAZ area,RLS,SFCT of SML group were significantly improved at 3mo(all P<0.05).In the observation group,only CRT,DRVD and SFCT were improved(all P<0.05).Other research items in the observation group were not significantly different from baseline(all P>0.05).At the last follow-up,the BCVA and RLS in the SML group were better than those in the observation group,and CRT was lower,SRVD and DRVD,perfusion area of CCL were larger(all P<0.05).On FAF,no change of treatment spots was found after treatment.No structural laser damage was observed on optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA),and no choroidal neovascularization was observed.·CONCLUSION:SML treatment of acute CSC can improve BCVA,RLS,and perfusion area of CCL,reduce CRT,increase SRVD and DRVD,and is safe.

Statistical Properties of X-Ray Bursts from SGR J1935+2154 Detected by Insight-HXMT

As one class of the most important objects in the universe,magnetars can produce a lot of different frequency bursts including X-ray bursts.In Cai et al.,75 X-ray bursts produced by magnetar SGR J1935+2154 during an active period in 2020 are published,including the duration and net photon counts of each burst,and waiting time based on the trigger time difference.In this paper,we utilize the power-law model,dN(x)/dx∝(x+x_0)~((-α)_x),to fit the cumulative distributions of these parameters.It can be found that all the cumulative distributions can be well fitted,which can be interpreted by a self-organizing criticality theory.Furthermore,we check whether this phenomenon still exists in different energy bands and find that there is no obvious evolution.These findings further confirm that the X-ray bursts from magnetars are likely to be generated by some self-organizing critical process,which can be explained by a possible magnetic reconnection scenario in magnetars.

OCTA联合微视野计在视网膜静脉阻塞黄斑水肿中的应用

目的:应用光学相干断层扫描血管成像(OCTA)联合微视野计对视网膜静脉阻塞(RVO)黄斑水肿患者的黄斑区微血管及视功能进行定量评价。方法:收集单眼RVO并发黄斑水肿患者36例36眼,其中视网膜中央静脉阻塞(CRVO)组15例15眼,视网膜分支静脉阻塞(BRVO)组21例21眼(均为颞上分支静脉阻塞),收集同期年龄匹配的健康人15例24眼作为对照组。三组均应用OCTA扫描黄斑3mm×3mm范围视网膜,定量浅层、深层毛细血管丛(SCP、DCP)的血流密度(VD)、黄斑中心凹无血管区(FAZ)面积及黄斑中央视网膜厚度(CRT);应用MP-3微视野计测量患者黄斑10°范围视网膜平均敏感度(RMS)。BRVO组将VD及RMS进一步区分为病变区(上方)、非病变区(下方)VD及RMS,对照组病变区及非病变区的划分依据BRVO组相对应的区域。分别比较CRVO组和BRVO组与对照组上述指标变化,并对CRVO组和BRVO组RMS与VD、CRT、FAZ面积进行相关性分析。结果:CRVO组整体VD(SCP和DCP)较对照组均减少(t=-2.536,P=0.016;t=-8.834,P<0.001);FAZ面积较对照组增大(t=3.354,P=0.002);CRT较对照组增加(t=13.888,P<0.001);整体RMS较对照组明显降低(t=-6.250,P<0.001)。BRVO组整体VD(SCP和DCP)较对照组均减少(t=-5.186,P<0.001;t=-5.238,P<0.001);病变区VD(SCP和DCP)较对照组相应区域均明显减少(t=-5.611,P<0.001;t=-6.940,P<0.001);未病变区VD(DCP)较对照组相应区域减少(t=-3.047,P=0.004),未病变区VD(SCP)较对照组相应区域无差异(t=-1.459,P=0.156);FAZ面积较对照组增大(t=2.722,P=0.011);CRT较对照组增加(t=7.764,P<0.001);整体RMS较对照组明显降低(t=-10.931,P<0.001);病变区及未病变区RMS较对照组相应区域均下降(t=-13.183,P<0.001;t=-8.074,P<0.001)。CRVO组整体RMS与整体VD(SCP和DCP)均呈正相关(r=0.571,P=0.026;r=0.813,P<0.001),与FAZ面积及CRT均呈负相关(r=-0.621,P=0.014;r=-0.533,P=0.041)。BRVO组整体RMS与整体VD(SCP和DCP)均呈正相关(r=0.465,P=0.034;r=0.611,P=0.003),与CRT呈负相关(r=-0.547,P=0.01),与FAZ面积无相关性(r=-0.421,P=0.057)。结论:OCTA与微视野计的联合应用,能够对RVO黄斑水肿患者黄斑区结构与功能进行对应式的定量评估,为临床决策者提供更详细的信息,以做好疾病的解释工作。

Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray

AIM:To study the differential expression of Annexin A1(ANXA1)protein in human gastric adenocarcinoma.This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma.METHODS:Purified gastric adenocarcinoma cells(GAC)and normal gastric epithelial cells(NGEC)were obtained from 15 patients with gastric cancer by laser capture microdissection.All of the peptide specimens were labeled as18O/16O after trypsin digestion.Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry(nanoRPLC-MS/MS).The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis.The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry(IHC).The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed.RESULTS:A total of 78 differential proteins were identified.Western blotting revealed that ANXA1 expression was significantly upregulated in GAC(2.17/1,P<0.01).IHC results showed the correlations between ANXA1protein expression and the clinicopathological parameters,including invasive depth(T stage),lymph node metastasis(N stage),distant metastasis(M stage)and tumour-lymph node metastasis stage(P<0.01).However,the correlations between ANXA1 protein expression and the remaining clinicopathological parameters,including sex,age,histological differentiation and the size of tumour were not found(P>0.05).CONCLUSION:The upregulated ANXA1 expression may be associated with carcinogenesis,progression,invasion and metastasis of GAC.This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.

Posterior scleral reinforcement combined with vitrectomy for myopic foveoschisis

AIM： To investigate the effects of posterior scleral reinforcement （PSR） combined with vitrectomy for myopic foveoschisis. ~ METHODS： Thirty-nine highly myopic eyes of 39 patients with myopic foveoschisis underwent PSR combined with vitrectomy. Best corrected visual acuity （BCVA）, refraction error, and the foveal thickness by optical coherence tomography （OCT） were recorded before and after the surgery, and complications were noted. RESULTS： The follow-up period was 12mo, and the main focus was on the results of the 12-month follow-up visit. The mean preoperative BCVA was 0.96±0.43 IogMAR. At the final follow-up visit, the mean BCVA was 0.46± 0.28 IogMAR, which significantly improved compared with the preoperative one （P =0.003）. The BCVA improved in 33 eyes （84.62%）, and unchanged in 6 eyes （15.38%）. At the end of follow-up, the mean refractive error was -15.13 ±2.55 D, and the improvement was significantly compared with the preoperative one （-17.53±4.51 D） （P= 0.002）. Twelve months after surgery, OCT showed complete resolution of the myopic foveoschisis and a reattachment of the fovea in 37 eyes （94.87%） and partial resolution in the remained two eyes （5.13%）. The foveal thickness was obviously reduced at 12-month follow-up visit （196.45±36.35um） compared with the preoperative one （389,32±75.56um） （P=0.002）. There were no serious complications during the 12mo follow-up period. CONCLUSION： PSR combined with vitrectomy is a safe and effective procedure for myopic foveoschisis with both visual and anatomic improvement.

Effects of hepatocyte growth factor on MMP-2 expression in scleral fibroblasts from a guinea pig myopia model

AIMTo investigate the effects of hepatocyte growth factor (HGF) on MMP-2 expression in scleral fibroblasts from guinea pig with LIM.

Posterior scleral reinforcement for the treatment of pathological myopia

AIM： To investigate the effects of posterior scleral reinforcement（PSR） in the treatment of pathological myopia.·METHODS： The study included 52 eyes in 43 patients with pathological myopia who underwent PSR（PSR group）, and 52 eyes in 36 age- and myopia-matched patients who did not undergo such treatment as control group. Axial length, refraction error, best corrected visual acuity（BCVA）, and macular scans by optical coherence tomography（OCT） were recorded at baseline, 6mo, 1, 3and 5y after the surgery, and the complications were noted.·RESULTS： There were no statistical differences in axial length, refractive error, or BCVA between the PSR group and the control group at baseline. At the end of the follow-up, the mean axial length was 29.79 ±1.26 mm in the PSR group, which was significantly shorter than that in the control group（30.78±1.30 mm）（P 〈0.01）, and the mean refractive error was-16.86 ±2.53 D in the PSR group, which was significantly lower than that in the control group（-19.18 ±2.12 D）（P 〈0.01）. A statistically significant difference in BCVA was found between the PSR group（0.51 ±0.25 log MAR） and the control group（0.62±0.26 log MAR） at the postoperative 5-year follow-up（P 〈0.01）. There were no serious complications during the 5-year follow-up period.·CONCLUSION： PSR can prevent axial elongation and myopia progression in eyes with pathological myopia.

Sodium valproate suppresses abnormal neurogenesis induced by convulsive status epilepticus

Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dentate gyrus and the subventricular zone. Simultaneously, proliferating stem cells tend to migrate to areas with obvious damage. Our previous studies have clearly confirmed the effect of sodium valproate on cognitive function in rats with convulsive status epilepticus. However, whether neurogenesis can play a role in the antiepileptic effect of sodium valproate remains unknown. A model of convulsive status epilepticus was established in Wistar rats by intraperitoneal injection of 3 mEq/kg lithium chloride, and intraperitoneal injection of pilocarpine 40 mg/kg after 18–20 hours. Sodium valproate(100, 200, 300, 400, 500, or 600 mg/kg) was intragastrically administered six times every day(4-hour intervals) for 5 days. To determine the best dosage, sodium valproate concentration was measured from the plasma. The effective concentration of sodium valproate in the plasma of the rats that received the 300-mg/kg intervention was 82.26 ± 11.23 μg/mL. Thus, 300 mg/kg was subsequently used as the intervention concentration of sodium valproate. The following changes were seen: Recording excitatory postsynaptic potentials in the CA1 region revealed high-frequency stimulation-induced long-term potentiation. Immunohistochemical staining for BrdU-positive cells in the brain revealed that sodium valproate intervention markedly increased the success rate and the duration of induced long-term potentiation in rats with convulsive status epilepticus. The intervention also reduced the number of newborn neurons in the subgranular area of the hippocampus and subventricular zone and inhibited the migration of newborn neurons to the dentate gyrus. These results indicate that sodium valproate can effectively inhibit the abnormal proliferation and migration of neural stem cells and newborn neurons after convulsive status epilepticus, and improve learning and memory ability.

Fuel source shift or cost reduction:Context-dependent adaptation strategies in closely related Neodon fuscus and Lasiopodomys brandtii against hypoxia

Oxygen is essential for most life forms.Insufficient oxygen supply can disrupt homeostasis and compromise survival,and hypoxia-induced cardiovascular failure is fatal in many animals,including humans.However,certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia.Here,we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxiaadapted species with different life histories,namely,Qinghai voles(Neodon fuscus)and Brandt’s voles(Lasiopodomys brandtii),under hypoxic(10%O_(2) for 48 h)and normoxic(20.9%O_(2) for 48 h)exposure.Kunming mice(Mus musculus)were used for comparison.Qinghai voles live in plateau areas under hypoxic conditions,whereas Brandt’s voles only experience periodic hypoxia.Histological and hematological analyses indicated a strong tolerance to hypoxia in both species,but significant cardiac tissue damage and increased blood circulation resistance in mice exposed to hypoxia.Comparative transcriptome analysis revealed enhanced oxygen transport efficiency as a coping mechanism against hypoxia in both N.fuscus and L.brandtii,but with some differences.Specifically,N.fuscus showed upregulated expression of genes related to accelerated cardiac contraction and angiogenesis,whereas L.brandtii showed significant up-regulation of erythropoiesis-related genes.Synchronized upregulation of hemoglobin synthesis-related genes was observed in both species.In addition,differences in cardiometabolic strategies against hypoxia were observed in the rodents.Notably,M.musculus relied on adenosine triphosphate(ATP)generation via fatty acid oxidation,whereas N.fuscus shifted energy production to glucose oxidation under hypoxic conditions and L.brandtii employed a conservative strategy involving down-regulation of fatty acid and glucose oxidation and a bradycardia phenotype.In conclusion,the cardiovascular systems of N.fuscus and L.brandtii have evolved different adaptation strategies to enhance oxygen transport capacity and conserve energy under hypoxia.Our findings suggest that the coping mechanisms underlying hypoxia tolerance in these closely related species are context dependent.

Erratum:“Gamma-ray bursts with extended emission:classifications,energy correlations and radiation properties”(2020,RAA,20,201)

As a result of an error by the authors,in the paper,one of the authors’names,“Xu-Juan Li”,was misspelled.The correct spelling of the name should be“Xiu-Juan Li”.

Flanibizumab Plus Combined Surgery for Treatment o Neovascular Glaucoma with Vitreous Hemorrhage

Background：Neovascular glaucoma （NVG） is a refractory glaucoma.The management of NVG is very difficult,and it is more difficult when combined with vitreous hemorrhage.The aim of this study was to investigate the effects of ranibizumab plus combined surgery for NVG with vitreous hemorrhage.Methods：A total of 26 eyes of 26 NVG patients with vitreous hemorrhage were recruited in this study.The patients aged from 36 to 63 years with a mean age of 51.97 ± 7.60 years.The mean intraocular pressure （IOP） was 46.38 ± 5.75 mmHg （1 mmHg =0.133 kPa） while being treated with the maximum medical therapy.The mean best-corrected visual acuities converted to logarithm of the minimum angle of resolution （logMAR BCVA） was 2.62 ± 0.43.All the patients underwent intravitreal injection of 0.5 mg （0.05 ml） ranibizumab combined with pars plana vitrectomy （PPV）,pars plana lensectomy （PPL） with a preserved anterior capsule,panretinal photocoagulation （PRP）,and trabeculectomy （intravitreal ranibizumab [IVR] ＋ PPV ＋ PPL ＋ PRP ＋ trabeculectomy）.The IOP and logMAR BCVA were the main outcome measures in this study.Results：The follow-up period was 12 months.The mean postoperative IOPs were 26.38 ± 3.75 mmHg,21.36 ± 3.32 mmHg,1 8.57 ± 3.21 mmHg,and 16.68 ± 2.96 mmHg,respectively at 7 days,1 month,3 months,and 12 months after PPV ＋ PPL ＋ PRP ＋ trabeculectomy.At the last follow-up,the mean IOP was significantly lower than the preoperative one （t =6.612,P =0.001）.At 7 days,1 month,3 months,and 12 months after PPV ＋ PPL ＋ PRP ＋ trabeculectomy,the mean logMAR BCVA were 1.30 ± 0.36,1.29 ± 0.37,1.29 ± 0.39,and 1.26 ± 0.29,respectively.At the last follow-up,the mean logMAR BCVA was significantly improved,and the difference was statistically significant compared with preoperative one （t =6.133,P =0.002）.The logMAR BCVA improved in 22 eyes （84.62%）,and remained stable in 4 eyes （15.38%）.The neovascularization in the iris and the angle regressed significantly in all patients 7 days after ranibizumab injection.No serious complications occurred during 12 months of the study.Conclusions：IVR ＋ PPV ＋ PPL ＋ PRP ＋ trabeculectomy can control IOP well and improve BCVA without severe complication for NVG patients with vitreous hemorrhage.

ntravitreal Ranibizumab for Aggressive Posterior Retinopathy of Prematurity

Retinopathy ofprematurity （ROP） is a proliferative disease that affects infants of young gestational age （GA） and low birth weight （BW）. Aggressive posterior ROP （AP-ROP） is a rapidly progressing and severe presentation of ROP. It is characterized as posterior location （zone 1 or posterior zone I1）, Stage 3, and with plus disease （arterial tortuosity and venous dilation）. It can quickly lead to retinal detachment and blindness if not treated in time.