Objective:To observe the clinical features and disease outcomes of patients with fundus lesions associated with novel coronavirus infection (COVID-19).Methods:A case series observational study was conducted.Eighteen eyes of 10 patients with COVID-19 related fundus lesions diagnosed in the First Affiliated Hospital of Zhengzhou University from December 2022 to February 2023 were included.The affected eyes were examined by best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, scanning laser fundus photography (SLO), infrared fundus photography, optical coherence tomography (OCT), visual field and microperimetry.After the diagnosis was confirmed, according to the patients' willingness, 6 patients were treated with mecobalamin, vinblastine, and Aescuven forte orally.The other 4 patients were treated with glucocorticoid and methylprednisolone tablets orally with an initial dose of 32 mg/d, and the dose was reduced by 4 mg every 5 days, and potassium chloride tablets, calcium carbonate tablets, and omeprazole enteric-coated capsules were taken orally.According to the diagnosis and treatment of acute macular neuroretinopathy (AMN), the patients were divided into glucocorticoid treatment group (4 cases, 7 eyes) and non-glucocorticoid treatment group (4 cases, 8 eyes).The patients were followed up for 4 weeks.The BCVA, retinal morphology and structure, retinal sensitivity and fixation stability were compared before and after treatment.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-1482-002).Written informed consent was obtained from each subject.Results:Among the enrolled 10 cases (18 eyes), there were 9 cases (17 eyes) of AMN, including 1 eye with Purtscher-like retinopathy (PLR), 1 eye with acute para-central medial maculopathy (PAMM), and 1 eye with multiple transient white dot syndrome (MEWDS).The SLO images of AMN patients showed redbrown irregular lesions in the fovea or parafovea of the macular area.The OCT images showed patchy strong reflection between the OPL and ONL in the fovea or parafovea of the macular area, and the adjacent EZ/IZ had different degrees of local fracture, and the reflection signal was disordered.The BCVA of the eyes after 4 weeks of treatment was higher than that before treatment, and the difference was statistically significant ( Z=-2.823, P<0.05).After 4 weeks of treatment, the retinal sensitivity of the eyes was (26.57±2.24)dB, which was significantly higher than that before treatment (24.17±2.73)dB ( t=-11.329, P<0.001).There was no statistically significant difference in LogMAR BCVA and retinal sensitivity between the AMN glucocorticoid treatment group and the AMN non-glucocorticoid treatment group before and after 4 weeks of treatment ( Z=-0.986, P>0.05; t=-1.656, P>0.05). Conclusions:The main manifestations of COVID-19 related fundus lesions are AMN, PAMM, PLR, MEWDS, etc.OCT, microperimetry and other auxiliary examinations can help to diagnose the disease.The visual impairment and fundus structural changes caused by COVID-19 gradually improve after 4 weeks of treatment.

Objective:To observe the clinical characteristics and treatment prognosis of patients with ocular toxocariasis (OT).Methods:A retrospective clinical trial. From March 2018 to September 2021, 40 eyes of 40 OT patients diagnosed by ophthalmic examination in the First Affiliated Hospital of Zhengzhou University were included in the study. All patients underwent best corrected visual acuity (BCVA) and scanning laser ophthalmoscope (SLO) examination. Color Doppler ultrasound flow imaging (CDFI), fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were performed in 25, 26 and 26 eyes, respectively. Among the 40 patients, there were 23 males (57.5%, 23/40) and 17 females (42.5%, 17/40). All patients were monocular. Thirty patients (75.0%, 30/40) were younger than 18 years old, with the mean age of (9.60±0.60) years. Ten patients (25.0%, 10/40) were great than or equal to 18 years old, with the mean age of (34.60±4.52) years. Thirty-three patients (82.5%, 33/40) lived in rural areas for a long time. There were 27 patients (67.5%, 27/40) with a history of contact with dogs and cats. In 40 eyes, peripheral granuloma (peripheral type), posterior pole granuloma (posterior pole type), vitreous opacity similar to endophthalmitis (turbid type) and hybrid type were 18(45.0%, 18/40), 11(27.5%, 11/40), 6(15.0%, 6/40) ang 5(12.5%,5/40), respectively. All patients were treated with drugs and/or surgery after definite diagnosis. There were 28 eyes of peripheral type, posterior pole type and hybrid type, 17 eyes were treated with surgery and 11 eyes with drug treatment, respectively. Five eyes with turbid type were only treated with drugs. In 40 patients, 33 patients participated in follow-up. The follow-up time after treatment was (18.78±9.44) months. The improvement of BCVA was observed. The number of eyes with different BCVA before and after treatment was compared by χ2 test or Fisher's test. Results:At the first visit, the BCVA ranged from light perception to 0.6, including 20 eyes with BCVA <0.1, 13 eyes with BCVA 0.1-0.3, and 7 eyes with BCVA >0.3. The posterior vitreous anterior limiting membrane was thickened in 24 eyes (60.0%, 24/40). There were 27 eyes (67.5%, 27/40) with lamellar vitreous opacity and 22 eyes (55.0%, 22/40) with peripheral/posterior pole granulomas. Among 25 eyes examined by CDFI, 14 eyes (56.0%, 14/25) showed characteristic stratified or diffuse opacity in vitreous body. Of the 26 eyes examined by FFA, 15 eyes (57.7%, 15/26) had "fern-like" leakage of retinal capillaries, and the lesion had a patchy non-perfused area. In 26 eyes examined by OCT, epiretinal membrane, cystoid macular edema and vitreoretinal traction were 8 (30.8%, 8/26), 5 (19.2%, 5/26) and 2 (7.7%, 2/26) eyes, respectively. At the last follow-up, compared with before treatment, the BCVA of 5 eyes with turbid type increased, and the difference was statistically significant ( P<0.05). In 28 eyes with peripheral type, posterior pole type and hybrid type, 17 eyes with surgical treatment improved BCVA, and the difference was statistically significant ( χ2=6.258, P<0.05). In 11 eyes only treated with drugs, BCVA remained unchanged, and the difference was not statistically significant ( χ2=0.594, P>0.05). Conclusions:OT patients are mostly children; retinal granulomas, gray-white hyperplastic membrane behind lens or vitreous stratified opacity are specific characteristics. OT is mainly treated by glucocorticoid drugs and vitrectomy.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” Conclusions The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Objective:To study the correlation between liver imaging reporting and data system (LI-RADS) category with tumor differentiation, Ki67 index, microvascular infiltration, and predictive prognosis in hepatocellular carcinoma (HCC).Methods:We retrospectively analyzed the clinical and radiological data of 178 patients with HCC who were confirmed by histopathological studies after liver resection between January 2015 and September 2020 at Lishui Central Hospital and Lishui People’s Hospital. There were 156 males and 22 females, with age of (57±10) years old. These patients were assessed for LI-RADS categories according to the 2018 version of LI-RADS, and they were divided into 4 groups according to the assessment results: 12 patients with LI-RADS-3 (the LI-RADS-3 group); 26 patients with LI-RADS-4 (the LI-RADS-4 group); 102 patients with LI-RADS-5 (the LI-RADS-5 group); and 38 patients with LI-RADS-M (the LI-RADS-M group). The patients' general information, tumor markers, pathology and other clinical data were recorded. Correlation analysis between the LI-RADS category with pathology was performed by the Kendall's tau-b test. Survival analysis between groups was performed by the Kaplan-Meier analysis. The Cox regression risk model was used to analyze the relationship between these variables with the risk of death.Results:The Kendall's tau-b test showed that LI-RADS category was positively correlated with the degree of tumor differentiation ( t=0.204, P=0.002), but not with microvascular infiltration and Ki 67 index ( P>0.05). All patients were followed up for 4.2 to 84.2 months (median follow-up 36.3 months). By the end of follow-up, 31 patients had died and 147 patients were alive. The cumulative 1-year and 3-year survival rates of the LI-RADS-5 group were 97% and 90% respectively, which were significantly higher than those in the LI-RADS-M group (81% and 63%), and the LI-RADS-4 group (96% and 81%), ( P<0.05). The cumulative 1-year and 3-year survival rates of patients in the LI-RADS-3 group were 100% and 67% respectively, and there was no statistically significant difference with the LI-RADS-5 group ( P>0.05). The Cox multivariate regression analysis showed that tumor glycoantigen 199 (>50 μl/ml) to be an independent influencing factor in survival of HCC patients ( HR=0.43, 95% CI: 0.24-0.76, P=0.004). Conclusion:The LI-RADS category of HCC was positively correlated with the degree of tumor differentiation, and patients with HCC meeting the LI-RADS-5 criteria had relatively better prognosis.

Objective:Investigate the relationship between dietary patterns and sarcopenia in a Chinese elderly population.Methods:Participants in this cross-sectional study were recruited from the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. The study population comprised 2 423 participants, with mean age of (67.6±5.2) years. Sarcopenia was defined based on the guidelines of the Asian Working Group for Sarcopenia. Three dietary patterns were derived by factor analysis: fruit and sweet pattern, traditional oriental pattern, and animal food pattern. The association between quartile categories of dietary pattern scores and the presence of sarcopenia was analyzed using multiple logistic regression models. Odds ratios ( OR) and 95% confidence interval ( CI) were calculated. Results:The prevalence of sarcopenia was 16.1%. After adjusting for confounding factors, compared with the lowest quartile, the adjusted OR ( 95%CI) of sarcopenia for the highest quintile of Fruit and sweet pattern score, Traditional oriental pattern score and Animal food pattern score were 1.06 (0.74, 1.50), 0.54 (0.34, 0.86), and 0.50 (0.33, 0.74), ( P for trend were 0.87,<0.01, and<0.001), respectively. Conclusions:The current study found that the traditional oriental pattern and animal food pattern has a protective relation for sarcopenia in elderly adults, which suggests its potential to attenuate or prevent the progression of sarcopenia.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Objective To analyze the chorological changes of diagnosis in patients with autoimmune liver disease (AILD) and related factors for early diagnosis.Methods A total of 581 patients with age ranged from 16 to 81 were retrospectively analyzed,who were admitted to Tianjin Medical University General Hospital with AILD during January 2000 to December 2017.Age at diagnosis,diagnostic method and cirrhosis at diagnosis were compared in different groups according to admission period as 2000-2005,2006-2011,2012-2017.Results The diagnostic rate of AILD showed an upward trend during the past near two decades.The proportion of AILD patients diagnosed via health examination was increasing year by year mainly by elevated transaminases (P＜0.001).The mean age at diagnosis in our AILD patients were younger at present,especially in men (P=0.044).The proportion of cirrhosis at diagnosis was gradually reduced in three different periods respectively [77.78％(21/27),41.58％ (79/190),25.00％(91/364),P＜0.001],which were coincident in patients with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (P＜0.001).The shrinking trend of cirrhosis at diagnosis was significantly correlated with the increasing application of health examination (r=-0.549,P＜0.001).Conclusions Extensive application of health examination expands the diagnostic rate of AILD.During the past 18 years,more young patients are diagnosed with AILD.The proportion of severe cases such as cirrhosis at diagnosis is decreasing.Screening of immunological examinations in patients with abnormal transaminases is needed and critical to the early diagnosis of asymptomatic AILD.

Objective To observe the clinical characteristics of multi-mode images of retinal arterial macroaneurysms and provide reference for the accurate diagnostic.Methods The clinic data of 24 patients (25 eyes) with retinal arterial macroaneurysms who were diagnosed in the First Affiliated Hospital of Zhengzhou University from August 2012 to May 2016 were retrospectively analyzed.All patients received ophthalmologic examinations including visual acuity,fundus photography,and fundus fluorescein angiography (FFA).The patients who could not be diagnosed by fundus photography and FFA underwent indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (SD-OCT) examinations.The visual acuity of the three types of retinal arterial macroaneurysms and the diameters of retinal arterial macroaneurysms based on FFA images was analyzed.Results A single macroaneurysm appeared in all the 25 eyes.Retinal arterial macroaneurysms of 22 eyes were on temporal artery branches and those of 3 eyes were on the nasal artery branches.Sixteen retinal arterial macroaneurysms were determined as hemorrhagic type,2 were exudative type and the other 7 were quiescent type.The difference of vision acuity in the three types of retinal arterial macroaneurysms was significantly different (x2=15.117,P=0.001).Retinal arterial macroaneurysms of 20 eyes could be clearly exhibited by FFA,and the retinal arterial macroaneurysms in other 5 eyes which were concealed due to bleeding were displayed by ICGA and OCT.The average diameter of retinal arterial macroaneurysms and normal arteries were (330.65±43.09)μm and (134.70±10.74)μm,respectively,showing a significant difference (t =21.034,P =0.000) and a positive correlation between them (r =0.867,P=0.000).Conclusions Most retinal artcrial macroaneurysms can be diagnosed by FFA,moreover,both ICGA and OCT can provide necessary supplement for the concealed retinal arterial macroaneurysms.The larger the diameter of the normal artery is,the larger the diameter of the corresponding retinal arterial macroaneurysms is.The typing of retinal arterial macroaneurysms can offer basis for the evaluation of management.

Objective To investigate the role of leukemia inhibitory factor (LIF) on retinal photoreceptor cells and the underlying mechanism after light damage.Methods Fifty 5-6 weeks old BALB/c mice were randomly divided into normal control group (10 mice),light damage+LIF group (20 mice) and light damage+PBS group (20 mice).Four days before exposing to light,the right eye of each animal in light damage+LIF group and light damage+PBS group was injected with LIF and PBS,respectively;then the mice in the light damage+LIF group and light damage+PBS group were exposed to 4 000 lx intensity of cool white fluorescent light for 4 hours to establish the experimental model of retinal light damage.The function and morphology of retinal photoreceptor cells were detected by flash electroretinogram (fERG) and histopathological examination.Real-time PCR was used to detect the mRNA expression of Jak3,STAT3,and apoptosis-related factor Bcl-2 and Bax.The use of animals is guided by the State Science and Technology Commission's regulations on the management of experimental animals.Results The amplitudes of scotopic ERG a wave of 0.01,1,100,200,400 cd · s/m2 light in the light damage + PBS group were significantly lower than those in the normal control group and light damage + LIF group (all at P ＜ 0.05).The amplitudes of photopic ERG b wave of different color light in the light damage+PBS group were significantly lower than those in the normal control group and light damage+LIF group (all at P＜0.05).The number of photoreceptor nuclei in the light damage+PBS group was significantly lower than that in the normal control group and light damage+ LIF group (both at P＜0.05).Compared with light damage+PBS group,the relative expression of Jak3,STAT3,Bcl-2 mRNA in light damage+LIF group were significantly increased (all at P＜0.05),and the relative expression of Bax mRNA were significantly decreased (P＜0.05).Conclusions LIF can protect retinal photoreceptor cells from light damage,which may result from the activation of Jak3/STAT3 signaling pathway and inhibition of its downstream Bax/Bcl-2 apoptotic pathway.