AIM: To investigate the effect of accommodation on peripheral refraction in patients with myopia.METHODS: Cross-sectional study. A total of 105 patients(105 eyes)with myopia were consecutively recruited in this study. According to the degree of myopia, patients were divided into high myopia(SE≤-6.00 D), moderate myopia(-6.00 D0.017).CONCLUSION: The accommodation can affect the peripheral defocus in myopic patients, and the effect on moderate and low myopia is greater than that of high myopia.

Objective To investigate the effect of orthokeratology(OK)lens decentration on peripheral retinal defo-cus in myopic eyes.Methods Totally 154 patients(234 eyes)continuously wearing OK lenses for one month or more were recruited in this study.According to the location of defocus rings in corneal topography,these eyes were divided into the centration group(118 eyes)and the decentration group(116 eyes).Peripheral retinal defocus data of each patient was collected by multispectral refraction topography,including total refraction difference value(TRDV),refraction difference value at 15°(RDV-15),refraction difference value at 30°(RDV-30),refraction difference value at 45°(RDV-45),superior refraction difference value(RDV-S),inferior refraction difference value(RDV-I),temporal refraction difference value(RDV-T)and nasal refraction difference value(RDV-N).An independent sample t-test was used to compare the differ-ences in these parameters between the two groups,and multivariate correlation analysis(generalized estimating equation,GEE)was conducted to analyze the relationship between clinical parameters and the amount of peripheral retinal defocus within the group.Results The RDV-N of patients in the decentration group was significantly lower than that in the cen-tration group(t=2.668,P=0.008),and there were no significant differences in other parameters(all P＞0.05).GEE showed that age was the determinant of RDV-S,and they were positively correlated;steep K was the determinant of RDV-I,and they were negatively correlated;gender was the determinant of RDV-T,and female OK lens wearers showed less RDV-T;the determinants of RDV-N include the alignment of OK lens,eye distribution and age,among which,RDV-N was positively corrected with age,and RDV-N of the left eyes was significantly superior to that of the right eyes.Conclusion Subclinical decentration of the OK lens may result in better RDV-N of myopia patients.The peripheral retinal defocus is influenced by factors such as age,gender,steep K,amount of decentration and eye distribution of OK lens wearers.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal chronic interstitial lung disease characterized by a progressive decline in lung function, and current treatment options are limited. cAMP is one of the most important second messengers and plays a key role in relaxing airway smooth muscle cells and reducing inflammation. Phosphodiesterase (PDE) is a superfamily of enzymes, and PDE4 enzymes dominate 11 PDE superfamily enzymes, available in four isoforms-PDE4A, PDE4B, PDE4C and PDE4D, which selectively decompose cAMP, while PDE4 inhibitors increase cAMP levels by preventing cAMP from breaking down, thereby exerting anti-inflammatory, anti-remodeling effects and providing an attractive drug target for the treatment of IPF. This review summarizes knowledge about the association of pulmonary fibrosis with PKE4, as well as emerging preclinical studies and clinical trials regarding PDE4 inhibitors.

Objective To investigate the association between serum alkaline phosphatase (ALP) and type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Methods A total of 599 patients with T2DM who were hospitalized in Department of Endocrinology, Affiliated Hospital of Jiangsu University, from July 2016 to December 2018 were enrolled as subjects. According to the presence or absence of NAFLD, the patients were divided into NAFLD group with 286 patients and non-NAFLD group with 313 patients, and according to the results of abdominal ultrasound, the patients with NAFLD were divided into mild group with 111 patients, moderate group with 105 patients, and severe group with 70 patients. General clinical data were compared between groups. The independent samples t - test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between three groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. Pearson correlation analysis and Spearman correlation analysis were used to investigate the correlation between ALP and clinical indices, and a logistic regression analysis was used to investigate the influencing factors for NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with history of hypertension ( χ 2 =7.864, P < 0.05), systolic blood pressure ( t =-2.226, P < 0.05), diastolic blood pressure ( t =-3.800, P < 0.05), body mass index (BMI) ( t =-11.842, P < 0.05), waist circumference (WC) ( t =-9.150, P < 0.05), fasting insulin (FINS) ( Z =-6.173, P < 0.05), fasting C-peptide ( t =-5.419, P < 0.05), serum uric acid ( t =-4.957, P < 0.05), low-density lipoprotein cholesterol ( t =-2.702, P < 0.05), triglyceride ( Z =-9.376, P < 0.05), total cholesterol (TC) ( t =-3.016, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( Z =-5.794, P < 0.05), alanine aminotransferase (ALT) ( Z =-6.737, P < 0.05), aspartate aminotransferase (AST) ( Z =-4.389, P < 0.05), gamma-glutamyl transpeptidase (GGT) ( Z =-7.764, P < 0.05), and ALP ( t =-2.833, P < 0.05), as well as significantly lower age ( t =2.184, P < 0.05) and high-density lipoprotein cholesterol ( Z =-5.273, P < 0.05). The severity of NAFLD (mild, moderate or severe) was positively correlated with age ( r s =0.140, P < 0.05), BMI ( r s =0.239, P < 0.05), WC ( r s =0.222, P < 0.05), FINS ( r s =0.191, P < 0.05), HOMA-IR ( r s =0.218, P < 0.05), ALT ( r s =0.188, P < 0.05), AST ( r s =0.279, P < 0.05), GGT ( r s =0.202, P < 0.05), and ALP ( r s =0.361, P < 0.05). In the patients with T2DM and NAFLD, ALP was positively correlated with HbAlc ( r =0.149, P < 0.05), fasting plasma glucose ( r =0.146, P < 0.05), HOMA-IR ( r s =0.132, P < 0.05), TC ( r =0.151, P < 0.05), ALT ( r s =0.210, P < 0.05), AST ( r s =0.192, P < 0.05), and GGT ( r s =0.297, P < 0.05). The logistic regression analysis showed that ALP was an influencing factor for NAFLD in patients with T2DM (odds ratio=1.013, 95% confidence interval: 1.004-1.023, P < 0.05). Conclusion Elevated serum ALP is a risk factor for T2DM with NAFLD and is closely associated with hyperglycemia, insulin resistance, and hyperlipemia, and ALP may play a role in the development and progression of T2DM and NAFLD.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

IPF is a chronic progressive interstitial lung disease of unknown etiology and poor prognosis, and despite receive treatment, most patients consideration are likely to progress or worsen. Integrins are heterodimer cell surface proteins that are promising therapeutic targets for intervention in pulmonary fibrosis. Alphav integrins are central to the development of fibrosis because they activate latent TGF-β, a known pro-fibrosis cytokine. The alphav subunit may form heterodimers with the β1, β3, β5, β6, or β8 subunits, one or more of which are essential for the development of pulmonary fibrosis, but their relative importance is unclear. This review summarizes the knowledge of the association of pulmonary fibrosis with alpha-val-integrins, as well as emerging preclinical studies and clinical trials of alpha-fibrosis inhibitors.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology, which is characterized by scarring of lung parenchyma, leading to reduced quality of life and premature death. At present, some studies have confirmed that hypothyroidism (HT) may play a role in the development of fibrosis. Many animal experiments have proved that thyroid hormone (TH) can inhibit pulmonary fibrosis by regulating glucose metabolism, improving mitochondrial function and inhibiting inflammation. This paper summarizes the correlation between TH and IPF, and deeply understands the relationship between TH and IPF, in order to have new treatment strategies for IPF in the future.

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34⁺ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34⁺ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Acrylamides/pharmacology* ; Animals ; Blood Platelets/drug effects* ; Cell Differentiation ; Megakaryocytes/drug effects* ; Mice ; Mice, Inbred C57BL ; Piperazines/pharmacology* ; Pyrimidines/pharmacology*

Objective:To evaluate the prognostic value of thromboelastography maximum amplitude(MA)and arterial blood lactate levels for sepsis in elderly patients.Methods:A retrospective analysis was performed on clinical data of 63 sepsis patients(≥60 years old)admitted to the Intensive Care Unit(ICU)of Bethune Hospital of Shanxi Province from December 2018 to February 2020.MA values, white blood cell counts, lymphocyte counts, platelets, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores, sequential organ failure assessment(SOFA)scores, underlying diseases, body mass index, laboratory test results and other related treatments were analyzed.The subjects were divided into the survival group and the death group according to the 28-day survival outcome.Differences in MA, APACHE Ⅱ scores, SOFA scores and laboratory test results between the two groups were analyzed, and the correlations of MA with infection parameters and age were examined.Influencing factors of survival outcomes were analyzed using multivariate Logistic regression.The receiver operating characteristic curve(ROC)was used to calculate the prognostic value of MA and arterial lactate for sepsis in elderly patients.Results:The main sources of infections were pulmonary and abdominal(79.4%, 50/63)in 63 elderly patients with sepsis.The incidences of positive blood cultures and deaths were 15.9%(10/63)and 66.7%(42/63), respectively.There existed significant differences in lymphocyte counts, arterial lactate levels, MA and lengths of stay in the ICU between the survival group and the death group( t=3.847, 2.153, 2.745, -3.574, respectively, all P<0.05).MA was correlated with arterial lactate, SOFA score and survival outcome( r=-0.498, -0.506, and -0.358, respectively, all P<0.05).Multivariate Logistic regression analysis showed that MA and arterial lactate were independent factors for the survival outcome( OR=1.626, 0.766, all P<0.05).The area under the ROC curve(AUC, 95% CI)for the combination of MA and arterial lactate was larger than that of either MA or arterial lactate alone(0.89, range: 0.763-0.846; 0.58, range: 0.574-0.730; 0.77, range: 0.521-0.832; all P<0.05). Conclusions:The combination of thromboelastography maximum amplitude and lactate in arterial blood has important clinical value in assessing the prognosis of elderly patients with sepsis.