Objective:To evaluate the efficacy and safety of dexamethasone intravitreal implant (Ozurdex) in treating the refractory macular edema caused by retinal vein occlusion (RVO).Methods:An observational case series study was conducted.Twenty-one eyes of 21 patients diagnosed as refractory macular edema secondary to RVO and treated with Ozurdex implant in Beijing Aier-Intech Eye Hospital from March 2016 to September 2019, who was with a course lasting longer than 3 months and received at least 2 times of anti-VEGF treatments, had recurrent macular edema and no visual improvement or even deteriorated, were included.Best corrected visual acuity (BCVA) was examined using standard visual chart and was converted to logarithm of the minimal angle of resolution (LogMAR) units and intraocular pressure (IOP) was examined.Optical coherence tomography (OCT) was used to measure central retinal thickness (CRT) in all eyes before and at 1, 2, 3 and 6 months after intravitreal injection of Ozurdex.The changes of BCVA, IOP and CRT before and after Ozurdex injection were observed and analyzed.During the 6-month follow-up, re-injection of Ozurdex or ranibizumab was adopted among those with macular edema recurrence or poor efficacy according to the subjects' conditions.Ocular adverse effects and potential systemic complications were observed.This study followed the Declaration of Helsinki and the study protocol was approved by an Ecthics Committee of Beijing Aier-Intech Eye Hospital (No.BJAIER2020IRB01).Results:The mean CRT at 1, 2, 3, 6 months after Ozurdex injection was (295.76±49.19), (280.33±39.44), (321.29±73.46), (300.29±75.10)μm, respectively, which were significantly decreased in comparison with (458.52±174.61)μm at baseline (all at P<0.05). There was no significant difference in mean BCVA at different time points before and after Ozurdex injection ( F=1.975, P>0.05). During the follow-up, 10 eyes had macular edema recurrence at 2 to 6 months after first Ozurdex injection, with an average of (4.1±1.5) months.Among them, 8 eyes received second Ozurdex injection, and CRT was significantly reduced and BCVA was significantly improved at 6 months after the second Ozurdex injection in comparison with those at recurrence ( t=5.254, P=0.001; t=4.277, P=0.004). The IOP was significantly elevated at 2 months after first Ozurdex injection in comparison with that at baseline ( P=0.01). Ocular hypertension (IOP≥25 mmHg) was oberserved in 3 (14.3%) eyes during the follow-up period but were well controlled after local application of eye drops.No vitreous hemorrhage, retinal detachment, endophthalmitis or other serious adverse effects or systemic complications were observed. Conclusions:One dose of intravitreal Ozurdex injection can significantly improve the structure and function of macula in refractory macular edema caused by RVO for 4 to 6 months and maintain the baseline visual acuity.Second administration of Ozurdex is still effective for recurrent RVO macular edema.Transitional IOP elevation is the main adverse event.

Objective:To investigate the efficacy and major adverse cardiovascular events(MACE)in elderly patients with ischemic cardiomyopathy-induced heart failure with reduced ejection fraction(HFrEF)treated with Sacubitril-valsartan at 3 years of follow-up.Methods:This was a single-center retrospective cohort study.The elderly patients with ischemic cardiomyopathy-induced HFrEF aged 60-85 years were diagnosed and treated in Beijing Anzhen Hospital from January 2018 to January 2020.A total of 120 continuously included elderly HFrEF patients treated with sacubitril valsartan were enrolled as the observation group, and 120 age-, gender-and B-type natriuretic peptide-matched elderly HFrEF patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blocker(ACEI/ARB)were enrolled as the control group.Structure and function of the heart were detected at 1-year follow-up.The MACE was observed, including cardiogenic death, readmission due to heart failure worsening and malignant arrhythmia at 3-year follow-up.Results:During follow-up(23.5±11.6)months, the visit of 18 cases was lost.There were no significant differences in the age, medical history, blood pressure between the two groups( P>0.05). Follow-up results showed that the improvement was better in observation group than in control group as follows: the left ventricular ejection fraction(45.8±9.4)% vs.(40.7±8.5)%, left ventricular end-diastolic diameter(56.5±8.3)mm vs.(59.2±7.3)mm, left ventricular end-systolic diameter(42.5±11.2)mm vs.(45.7±9.6)mm, left atrium inner diameter(49.1±8.7)mm vs.(51.2±7.7)mm, and left ventricular mass index(111.3±34.3)g/m 2vs.(119.7±31.5)g/m 2( t=4.41, 2.68, 2.38, 1.98 and 1.98, respectively, P<0.01 or 0.05). The rates of readmission due to heart failure worsening and the incidence of MACE were lower in the observation group than in the control group(21.7% or 26/120 vs.36.7% or 44/120, and 45.0% or 54/120 vs.71.7% or 86/120, χ2=6.54 and 17.55, P<0.05 or 0.01). In patients with the grade Ⅲ and Ⅳ New York Heart Association(NYHA)cardiac function, the incidence of MACE were lower in the observation group than in the control group(75.0% or 9/12 vs.100.0% or 14/14, χ2=5.10, P<0.05). Conclusions:Sacubitril-valsartan can improve cardiac structure and function, and decrease the incidence of MACE in elderly patients with HFrEF induced by ischemic cardimyopathy.

AIM: To study the efficacy and safety of Ultra Q- YAG vitreolysis for vitreous floaters.
METHODS: Retrospective case series study. From September 2014 to May 2015 in Beijing Aier - Intech Eye Hospital, 263 cases (340 eyes) with vitreous floaters were involved. All patients underwent visual acuity, intraocular pressure, slit lamp, mydriatic fundus, B ultrasonic examination, and recorded the form of a vitreous opacity excluded pathological fundus lesions. All the patients were divided into two groups: Group A (<30 years old) 78 cases (82 eyes); the morphology of vitreous opacity were dot, filiform and mesh. Group B ( > 45 years old), 185 cases (258 eyes), the morphology of vitreous opacity was Weiss ring, translucent flocculent clouds or dense fibrous membrane. Patients in 30 - 45 years old were eliminated because of the untypical opacity factor. The treatment was done by the same physician. Vision changes was analyzed before and after the treatment.
RESULTS: Questionnaire survey was done. According to the scores of the questionnaires, patients were divided into 3 groups: no improvement ( 1 - 2 points), partial improvement (3-5 points), significant improvement (6-10 points ). At 1mo after treatment, Group A: no improvement in 9 eyes (11. 0%), partial improvement in 57 eyes (69. 5%) and significant improvement in 16 eyes (19. 5%); Group B: no improvement in 0 eyes, partial improvement in 23 eyes ( 8. 9%) and significant improvement in 235 eyes (91. 1%); all the patients had no complications.
CONCLUSION: The treatment with YAG vitreolysis for vitreous floaters is safe and effective, especially for the patients more than 45 years old whose vitreous floaters caused by posterior vitreous detachment.

Objective:To study the association between rs2235371,rs2013162,rs2235377 SNPs in interferon regulatory factor 6 (IRF6)gene and non-syndromic cleft lip with or without cleft palate(NSCL/P)in Xinjiang Uyghur population.Methods:100 Uyghur NSCL/P patients from Xinjiang were included in the case group and 60 Uyghur inpatients with upper respiratory tract infection were se-lected in the control group.Next,generation sequencing was used,DNA sequencing results were compared with the information on the genome database and genetic analysis were made.Results:There were no significant differences in the frequency distribution of both genotypes and alles when the cases were campared with the controls at the rs2235371,rs2013162 and rs2235377 loci(P >0.05). Above three loci were located in the same block,rs2235371 and rs2235377 loci presents the strong linkage disequilibrium(r2 =0.949, D'=0.974).Possible haplotypes were:CCT >CAT >TAC,and there was no significant difference between the cases and controls in haplotype distribution(P >0.05).Conclusion:Polymorphisms of rs2235371,rs2013162 and rs2235377 in IRF6 gene may be associ-ated with NSCL/P in Xinjiang Uygur people.

Objective To determine the incidence and effect of unrecognized cardiac injury in critically ill patients and evaluate the significance of elevations of serum troponin Ⅰ and APACHE Ⅱscore in patients with critically illness.Methods We measured the level of serum troponin Ⅰ and evaluated relationship between elevations of serum troponin Ⅰ and APACHE Ⅱ score,myocardial injury,mechanical ventilation,intensive care unit stay by means of retrospective chart review and analysis of clinical data.Results Thirty-four(21.4%)of the 159 patients had evidence of myocardial injury based on elevated levels of cardiac troponin Ⅰ,only 9(26.5%)of these 34 patients were diagnosed as having acute myocardial infaction by the intensive care unit staff.Mortality in patients with myocardial injury that was unrecogniazed(41.2%)or recognized(44.4%)was higher than in those without myocardial injury(16.0%)(P

Transforming growth factor β(TGF-β)superfamily ligands play an important role in regulating cellular homeostasis including proliferation,differentiation,apoptosis,immune sur-veillance and angiogenesis.Type Ⅲ TGF-βreceptor (TβRⅢ) is considered to be the coreceptor of TGF-βsuperfamily.TβRⅢnot only has an effect on classical Smad signaling pathway,but also on non-Smad signaling pathway.TβRⅢplays a crucial role in fibrosis,tumor,cardiovascular diseases via mediating kinds of signaling pathways.This paper reviews TβRⅢ mediated sig-naling pathway and its role in fibrotic diseases.

Objective·To analyse the outcomes of tricuspid valve replacement (TVR) for secondary tricuspid regurgitation (STR) late after left-sided valve surgery during perioperative period and mid-term follow-up,investigate mechanisms of STR and surgical risk factors.Methods·A total of 85 consecutive patients who underwent the TVR surgery were analyzed.The perioperative and mid-term clinical outcomes were retrospectively investigated.The data were divided into bioprosthesis group (n=50) and mechanical prosthesis group (n=35) according to the prosthesis used,and divided into right anterolateral thoracotomy(RALT) group (n=51) and stemotomy(S) group (n=34) according to the surgical incision.Results·In-hospital mortality was 8.2％ (7/85).There was no significant difference in the mortality with different choice of bioprosthetic or mechanical valve (4/50 vs 3/35,x2=0.009,P=1.000);while there was significant difference between S group and RALT group (6/34 vs 1/51,x2=6.642,P=0.015).Seven cases all died of right heart failure and severe low cardiac output syndrome.Five (5.9％) cases died in perioperative within 30 in-hospital days and 2 (2.4％) cases died after 30 in-hospital days.Seventy-four cases were followed up.With the follow-up of (31.5±23.1) months,there were 4 case of late deaths(5.4％),all of whom were mechanical prosthesis,of whom 3 died in cardiac related death and 1 died in later period bowel cancer.Seventy cases survived in New York Heart Association (NYHA) class Ⅰ-Ⅱ with no coagulated accident and redo-TVR.Conclusion·The perioperative and mid-term clinical outcomes are satisfied in timely and reasonable TVR with the standard follow-up for STR late after left-sided valve surgery.Right anterolateral incision is recommend for isolated TVR.

Objective To investigate miR-146a-Smad4 expression during ultraviolet A(UVA)-induced photoaging of human skin fibroblasts (HSFs), and to evaluate effects of up-regulation of miR-146a expression on its target gene Smad4 and cell photoaging. Methods HSFs were isolated from the prepuce, and subjected to primary culture and maintained up to 10th passage. Then, the HSFs were classified into 4 groups: blank control group receiving no treatment, UVA group irradiated with 10 J/cm2 UVA, miR-146a group transfected with a lentiviral vector expressing miR-146a, UVA+ miR-146a group transfected with the lentiviral vector expressing miR-146a followed by UVA radiation. Real time PCR was performed to measure miR-146a expression in HSFs in the UVA group on day 0, 3, 7 and 14 after UVA radiation.Fluorescence microscopy was carried out to estimate transfection efficiency on day 7 and 14 in the miR-146a group after transfection, and real time PCR was performed to quantify miR-146a expression in these cells. Methyl thiazolyl tetrazolium (MTT)assay was conducted to evaluate proliferative activity of HSFs, real time PCR to quantify mRNA expressions of photoaging-related genes p53, p21 and p16, and Western blot analysis to measure Smad4 protein expression in these cells. Statistical analysis was carried out by using repeated-measures analysis of variance and factorial design analysis of variance. Results Repeated-measures analysis of variance showed that the expression of miR-146a decreased over time in both the UVA group and blank control group(F = 213.840, P < 0.01), and significantly lower in the UVA group than in the blank control group (F = 52.55, P < 0.01), with the difference between the two groups increasing over time. After transfection with the lentiviral vector expressing miR-146a-Smad4, HSFs showed a strong fluorescence intensity of miR-146a. The expression level of miR-146a was significantly higher in the miR-146a group than in the blank control group on day 7 and 14 after transfection(10.31 ± 0.17 vs. 8.33 ± 0.13 on day 7, 9.65 ± 0.19 vs. 7.86 ± 0.11 on day 14, F =42.49, P < 0.01), but insignificantly different between day 7 and 14 in the miR-146a group (P > 0.05). Factorial design analysis of variance showed that UVA radiation had an inhibitory effect on the proliferative activity of HSFs (P < 0.01), which was significantly lower in the UVA group than in the blank control group(P < 0.01), and lower in the UVA + miR-146a group than in the miR-146a group (P < 0.01). The lentivirus-mediated up-regulation of miR-146a expression also affected cellular proliferative activity (P < 0.01), which was significantly higher in the UVA + miR-146a group than in the UVA group(P < 0.01), but insignificantly different between the miR-146a group and blank control group(P > 0.05). Real time PCR and Western blot analysis both revealed that UVA radiation could increase the expressions of p53, p21 and p16 mRNAs as well as Smad4 protein(all P < 0.01). Concretely speaking, the expressions of p53, p21, p16 mRNAs and Smad4 protein were all significantly higher in the UVA group than in the blank control group (all P < 0.01), and higher in the UVA +miR-146a group than in the miR-146a group (all P < 0.01), but significantly lower in the UVA + miR-146a group than in the UVA group (all P < 0.01), and insignificantly different between the blank control group and miR-146a group (all P >0.05). Conclusion The expression of miR-146a is inhibited in UVA-induced photoaged HSFs, and its up-regulation may counteract cell photoaging by suppressing Smad4 expression in, and promoting proliferation of, photoaged HSFs.

AIM:To study the effect of ?1-adrenergic agonist on alveolar fluid clearance in hypoxic rat lungs. METHODS: Rats were exposed to 10% oxygen. Alveolar fluid clearance (AFC) and lung water content (TLW) were calculated in rats exposed to hypoxia for 24 h and 48 h. Isotonic 5% albumin in solutions with different pharmacological agents were instilled into the distal airways in the hypoxia exposed and room air-exposed rat lungs, and the AFC was examined. RESULTS: As compared with the room air-exposed rats (17.50%?2.66%), AFC in the rats exposed to 10% oxygen was not decreased (18.70%?3.19%), AFC in the rats exposed to 10% oxygen for 48 h was decreased (8.59%?2.60%). Denopamine, a ?1-adrenergic agonist, increased AFC significantly in the rats exposed to room air and hypoxia. The potency of 10-5 mol/L denopamine was similar to that of 10-5mol/L terbutaline. The denopamine effect was partly blocked by inhibitors of sodium transport amiloride and ouabain (AFC were 11.80%?2.79% and 8.53%?2.17%). CONCLUSION: Denopamine, a selective ?1-adrenergic agonist, stimulates alveolar fluid clearance in rats exposed to hypoxia through the active sodium transport, and may have therapeutical effect on pulmonary edema after acute lung injury.

Objective To study the effects of Fasudil on expression of Nogo-A and NF200 in neonatal hypoxic-ischemic brain damage(HIBD) rats.Methods One hundred and twenty 7-day-old Wistar rats were divided into 3 groups with random number table:Sham operation group (n =40),HIBD group (n =40) and Fasudil group (n =40).Sham group only separated from the common carotid artery,without ligation,direct suture the incision does not do hypoxia; HIBD group were injected with saline; Fasudil group was injected with fasudil(10 mg/kg).The rats were killed at 6 h,12 h,24 h,72 h,7 d,after administration.The pathological changes were observed by means of HE.The expression of Nogo-A and NF200 was studied with immunohistochemical staining.Results 1.Naked eye observation:Sham group bilateral symmetrical cerebral hemispheres; HIBD group of brain edema aggravated,the visible hemisphere focal necrosis; fasudil treatment group of edema than HIBD group ease.2.HE stain:the structure and shape of brain in Sham operation group were normal.In HIBD group,the cells became edema,karyopyknosis,lyse,and the inflammatory cells became more.The number of edema cells and karyopyknosis decreased in Fasudil group.3.Immunohistochemical stain:there were less expressions of Nogo-A in Sham operation group.It increased slightly after 12 h in HIBD group but decreased later.The expression of Nogo-A in Fasudil group was less than the other two groups at any time except 6 h (P ＜0.01).There was more expression in HIBD and Fasudil group compared with Sham operation group(P ＜0.01).NF200 was less expression in Sham operation group.NF200 appeared after 6 h and became less after 12 h.The expression of NF200 was at 24 h and later became more.The expression of NF200 in Fasudil group was more with HIBD group at each different time (P ＜ 0.01).The expressions of NF200 in Fasudil and HIBD group were more compared with Sham operation group.Conclusions Fasudil can rehabilitate the damaged axon and promote nerve regeneration through controlling the Rho/Rock and make the expression of NF200 increase.