Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0～35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.

Objective:To analyze the effect of vitrectomy combined with internal limiting membrane (ILM) peeling on the prevention of post-vitrectomy epiretinal membrane (ERM) in macular-off rhegmatogenous retinal detachment (RRD) and its influence on visual outcomes.Methods:A cohort study was conducted.Seventy-four patients (74 eyes) with macular-off RRD, who realized retinal reattachment after vitrectomy and silicone oil tamponade from January 2015 to January 2018 in Baoding NO.1 Central Hospital, were enrolled.The patients were divided into the non-ILM peeling group (36 cases, 36 eyes) and ILM peeling group (38 cases, 38 eyes) according to whether they received ILM peeling or not.The patients underwent silicone oil removal within 3 to 5 months after the surgery.Best corrected visual acuity (BCVA), slit-lamp microscopy, indirect ophthalmoscopy, fundus photography and optical coherence tomography (OCT) were examined before and at 1, 6 and 12 months after the surgery.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Baoding NO.1 Central Hospital (No.[2019]042). Written informed consent was obtained from each patient.Results:There was no ERM found in the two groups at 1 month after the operation.There were 3 eyes (8.33%) with ERM in the non-ILM peeling group and 2 eyes (5.26%) in the ILM peeling group at 6 months after the operation, with no statistically significant difference between them ( P=0.067). There were 9 eyes (25.00%) with ERM in the non-ILM peeling group and 4 eyes (10.53%) in the ILM peeling group at 12 months postoperatively, with no statistically significant difference between them ( χ2=2.674, P=0.102). There was a significant difference in BCVA between before and after the operation in the two groups ( Ftime=31.692, P<0.001). Postoperative 1-, 6-and 12-month BCVA were all significantly better than the preoperative BCVA in the two groups (all at P<0.05). There was no significant difference in BCVA between the two groups ( Fgroup=0.117, P=0.773). OCT images showed that there were 25 eyes (77.78%) and 30 eyes (78.95%) with the intact ellipsoid zone in the non-ILM peeling group and ILM peeling group at 12 months after the operation, respectively, with no statistically significant difference between them ( χ2=0.875, P=0.350). Conclusions:Compared with vitrectomy alone, the vitrectomy combined with ILM peeling does not show better efficacy in the prevention of ERM occurrence in macula-off RRD patients and has no obvious influence on postoperative visual acuity.

Objective : To analyze and compare the gene chip data of normal people and patients with acute myocardial infarction through GEO gene expression database , to screen out differentially expressed genes (DEGs) , and to predict potential Chinese medicines for the treatment of acute myocardial infarction. Methods : GSE66360 gene microarray was downloaded , DEGs information was obtained by analysis , gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differential genes were performed , key genes were further analyzed by String database and Cytoscape software , and key genes were mapped to the medical ontology information retrieval platform (Coremine Medical) to screen potential Chinese medicines for the treatment of acute myocardial infarction. Results : A total of 943 differentially expressed genes were screened. The biological process was mainly enriched in myeloid leukocyte activation , regulation of cytokine production , leukocyte chemotaxis , etc. The cellular component was mainly focused on secretory granule lumen , membrane surface , and extrinsic components of the membrane , etc. Molecular function was mainly in chemokine receptor binding , pattern recognition receptor activity , cytokine binding , etc. KEGG analysis showed that the main signaling pathways involved were tumor necrosis factor (TNF) , hypoxia inducible factor⁃1 (HIF⁃1) , and JAK⁃STAT signaling pathways , etc. The key genes to be screened are formyl peptide receptor 2 (FPR2) , signal transducer and activator of transcription 3 (STAT3) , chemokine (C - X - C motif) ligand 1 ( CXCL1) , chemokine ( C ⁃X ⁃C motif) ligand 8 ( CXCL8) , ubiquitin protein ligase E3 component n⁃recognin 4 ( UBR4 ) , jun proto⁃oncogene ( JUN ) , platelet⁃activating factor receptor (PTAFR) , Fc fragment of IgE , high affinity I , receptor for; gamma polypeptide (FCER1G) , G protein⁃coupled receptor 84 (GPR84) , plasminogen activator, urokinase (PLAU) . The potential herbs predicted for the treatment of acute myocardial infarction were Centipede (P = 0. 003 30) , Rithoma Curcuma (P = 0. 002 39) , Curcuma (P = 0. 002 40) , Paris polyphylla Smith (P = 0. 002 48) , Salviae miltiorrhizae (P = 0. 002 72) , Fritillary bulb (P = 0. 003 71) , and Panax ginseng (P = 0. 001 59) . Conclusion Traditional Chinese medicines such as Rithoma curcuma in activating blood and removing blood stasis medicine , Panax ginseng in nourishing Qi , and Fritillary bulb in medicine for the treatment of cough and asthma have protective effects on acute myocardial infarction. The mechanism of action may be related to the regulation of immune and anti⁃inflammatory signaling pathways.

ObjectiveTo investigate the possible mechanism of different doses of L-Borneolum，Borneolum，and Borneolum Syntheticum in the electrophysiology，anti-inflammation，and regulation of hypoxia inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） cardiovascular protection of the experimental acute myocardial infarction （AMI） rats. MethodSD male adult rats were randomly divided into thirteen groups according to their body weight，namely the sham operation group，the model group，the solvent model group，the nitroglycerin group，the Borneolum high，medium，and low-dose （0.6，0.3， 0.15 g·kg^-1） groups，the L-Borneolum high，medium，and low-dose （0.2，0.1， 0.05 g·kg^-1） groups，and the Borneolum Syntheticum high，medium，and low-dose （0.2，0.1， 0.05 g·kg^-1） groups，with 10 rats in each group. Rats were given 10 mL·kg^-1 by gavage for 3 d of pre-administration. Thirty minutes after the last administration，the left anterior descending coronary artery （LAD） was ligated to induce the model，and the successful rat model was continuously treated for 3 d. BL-420N biosystem was used to analyze the electrocardiogram （ECG） and heart rate variability （HRV） before and after modeling and after 3 d of treatment. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expressions of interleukin-1β （IL-1β） and interleukin-6 （IL-6） in the myocardial tissue Western blot and immunohistochemistry were used to determine the protein expression levels of VEGF receptor 1 （VEGFR1），HIF-1α，and CD34. ResultCompared with the sham operation group，the model group significantly increased the heart rate，ECG ST wave，T wave，QRS duration，QTC interval，and Q wave on the day of modeling and after 3 d of treatment，and significantly changed HRV and T wave （P<0.05，P<0.01）. As compared with the solvent model group，on the day of modeling，the heart rate of the L-Borneolum medium and low-dose groups and the Borneolum groups，the ST wave of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，HRV parameters of the L-Borneolum groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high-dose group，LF/HF of the L-Borneolum high and medium-dose group，the Borneolum low-dose group，and the Borneolum Syntheticum groups，T wave of the L-Borneolum high-dose group，the Borneolum Syntheticum high-dose group，and Borneolum medium-dose group，QTC interval of the L-Borneolum medium and low-dose groups and the Borneolum high and medium-dose groups，and QRS duration of the L-Borneolum high and low-dose groups，the Borneolum high and low-dose groups，and the Borneolum Syntheticum groups were significantly reduced or shortened （P<0.05，P<0.01）. After 3 d of treatment，the heart rate of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum medium-dose group，ST wave of the L-Borneolum group，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，OTC interval，ORS duration，and Q wave of the L-Borneolum high-dose group，the Borneolum high-dose group，and the Borneolum Syntheticum high and medium-dose groups，QRS duration of the L-Borneolum medium-dose group，QTC interval of the Borneolum medium-dose group，and Q wave of the Borneolum Syntheticum low-dose group were all significantly reduced or shortened（P<0.01）. The mRNA expressions of IL-1β and IL-6 in the L-Borneolum medium and low-dose groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high and medium-dose groups were significantly down-regulated（P<0.01），and LF/HF in the L-Borneolum high and medium-dose groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high and low-dose groups were significantly reduced （P<0.05，P<0.01）. HRV in the L-Borneolum high-dose group，the Borneolum groups，and the Borneolum Syntheticum high and low-dose groups，and T wave in the Borneolum high and medium-dose groups and the Borneolum Syntheticum high-dose group were increased significantly. The protein expressions of HIF-1α，VEGFR1，and CD34 in the L-Borneolum medium and low-dose groups，the Borneolum low-dose group，and the Borneolum Syntheticum high-dose group were significantly up-regulated，as well as those of VEGFR1 and CD34 in the Borneolum medium-dose group （P<0.05，P<0.01）. ConclusionThe 3 kinds of Borneolum improves the heart rate，heart rate variability，and electrocardiogram of AMI model rats to different degrees，and may play a myocardial protective effect by anti-inflammation and promotion of angiogenesis. The combined effect suggests that L-Borneolum has the superior effect next to Borneolum，and Borneolum Syntheticum has the inferior effect.

ObjectiveTo explore the active components and underlying mechanism of Huanglian Houpotang （HHD） against ulcerative colitis（UC） based on network pharmacology and animal experiments. MethodThe active components of HHD were preliminarily obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM） and screened out by TCMSP， SwissADME， and SwissTargetPrediction， and their targets were predicted. Relevant microarrays were searched for disease genes with the help of Gene Expression Omnibus （GEO）. The common targets of HHD and disease genes were screened out to obtain the potential targets of HHD against UC. The drug-active component-target-disease network was constructed using Cytoscape 3.7.2. The potential therapeutic targets were imported into the DAVID 6.8 for GO-Biological process （GO-BP） analysis to predict related biological processes which were subsequently verified by the animal experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the effect of HHD on inflammatory factors in colon tissues of mice. Western blot was used to detect the protein expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific protease 3 （Caspase-3）. The IVIS system was used to detect the content of reactive oxygen species （ROS） in colon tissues of mice in each group. ResultNineteen active components of HHD were screened out， involving 32 potential therapeutic targets against UC and 158 biological processes. The results of the animal experiment showed that HHD exerted its anti-UC effect by inhibiting the expression of inflammatory factors tumor necrosis factor （TNF）-α and interleukin-1β （IL-1β）， reducing the content of apoptotic proteins， and regulating the expression of ROS. ConclusionThis study revealed the rationality of predictions and guidance of network pharmacology in experimental design， and confirmed that HHD could exert its effects by participating in biological processes such as immune inflammation， apoptosis， and ROS， which is expected to provide a basis for the mechanism research of HHD in the treatment of UC.

Adhering to and strengthening the Party′s overall leadership is the primary guarantee for promoting the high-quality development of public hospitals. How to comprehensively strengthen the internal audit led by the Party and improve the efficiency of internal audit governance in public hospitals, so as to play the role of internal audit in effectively promoting the high-quality development of public hospitals, is an urgent problem to be solved. The author analyzed the current situation and practical reasons of the internal audit under the Party′s control in public hospital in China, constructed the mechanism framework of the internal audit under the Party′s control, and further analyzed and processed the implementation path of the internal audit under the Party′s control from three aspects: establishing the Party Committee Audit Committee to strengthen the top-level design of the internal audit, linking the three major audits to give full play to the supervision force of the internal audit, and implementing the eight major restructuring to achieve the closed-loop governance of the internal audit under the Party′s control.

Objective:To observe the effect of intravitreal injection of anti-vascular endothelial growth factor drugs on the subfoveal choroid thickness (SFCT) of patients with retinal vein occlusion (RVO) and macular edema (ME).Methods:A prospective clinical study. From January 2017 to January 2019, 59 monocular RVO-ME patients with 59 eyes diagnosed in the eye examination of The First Central Hospital of Baoding were included in the study. Among them, there were 31 males with 31 eyes and 28 females with 28 eyes; the average age was 57.4±10.3 years old. The course of the disease was 5 days to 1 month, all of whom had the first-onset disease. Branch retinal vein occlusion (BRVO) was found in 35 eyes (BRVO-ME group); non-ischemic central retinal vein occlusion (CRVO) was found in 24 eyes (CRVO-ME group). Best corrected visual acuity (BCVA) and frequency domain optical coherence tomography (OCT) were performed. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. The Cirrus HD-OCT 5000 instrument from Carl Zeiss company of Germany was used to measure the central macular thickness (CMT) and SFCT. All eyes were treated with intravitreal injection of anti-vascular endothelial growth factor drugs. The follow-up time after treatment was 6 months, and the changes of BCVA, CMT and SFCT of eyes before treatment and 2 weeks after treatment were compared and observed, as well as the occurrence of treatment-related complications. The comparison of BCVA, CMT, and SFCT at different times before and after treatment were adopted repeated measures analysis of variance; pairwise comparison of differences at different time points adopts the least significant difference t test. Results:Before treatment, the average logMAR BCVA and CMT of RVO-ME eyes were 0.92±0.46 and 604.71±169.35 μm, respectively. At 2 weeks, 1, 3, and 6 months after treatment, the average logMAR BCVA of the affected eye was significantly improved compared with that before treatment, and the CMT was significantly decreased. The difference was statistically significant ( F=55.664, 59.518; P<0.05). Before treatment, the average SFCT of the affected eye and the contralateral eye of RVO-ME patients were 306.3±65.8 and 241.3±59.8 μm, respectively. The SFCT of the affected eye was significantly thicker than that of the contralateral healthy eye, and the difference was statistically significant ( t=25.772, P<0.05). At 2 weeks, 1, 3, and 6 months after treatment, the average SFCT of the eyes were 267.7±81.4, 252.3±57.3, 239.2±46.5, 240.6±48.3 μm, respectively. Compared with before treatment, treatment SFCT decreased significantly at different times afterwards, and the difference was statistically significant ( F=924.341, P<0.001). There was no significant difference in SFCT between CRVO-ME group and BRVO-ME group at 2 weeks, 1, 3, and 6 months after treatment ( P>0.05). No complications such as endophthalmitis, cataract progression and neovascular glaucoma occurred during the follow-up period of all eyes. Conclusion:The SFCT of eyes with short course of disease and first-onset RVO-ME is thickened; anti-VEGF drug treatment can effectively reduce SFCT, improve ME, and increase BCVA.

Objective:To evaluate the changes of metamorphopsia in patients with rhegmatogenous retinal detachment (RRD) who underwent primary vitrectomy and to analyze the correlation between macular microstructure changes and metamorphopsia.Methods:It was a retrospective clinical study. From January 2017 to January 2019, 57 patients (57 eyes) with RRD were examined and diagnosed in the Department of Ophthalmology of Baoding First Central Hospital were enrolled in this study. All patients underwent 23G PPV. All patients had retinal anatomical reduction after the first PPV. The best corrected visual acuity (BCVA), intraocular pressure, slit-lamp microscope, indirect ophthalmoscope, changes of metamorphopsia, and optical coherence tomography (OCT) were examined before PPV and 1, 6, 12 months after the operation. The BCVA examination was performed using the international standard visual acuity chart, which was converted into a logarithm of the minimum angle of resolution (logMAR) BCVA for the record. The macular fovea retinal thickness (CRT) was measured by Carl Zeiss Cirrus HD-OCT5000 instrument from Carl Zeiss Company, Germany, and the microstructural changes in the macular area were recorded, including the presence of the anterior macular membrane (ERM), cystic macular edema (CME), subretinal fluid (SRF), and the integrity of the ellipsoid zone (EZ) and outer membrane (ELM). The value of metamorphopsia (M value) was measured by the M-Chart table. The changes of BCVA, M value, and the microstructure of the macular area before and after operation were analyzed. The correlation between BCVA and M value was analyzed by Pearson correlation. Spearman correlation analysis was used to analyze the correlation between the changes of macular microstructure and BCVA and M values.Results:The mean logMAR BCVA before the operation was 1.15±0.43. At 1, 6, and 12 months after the operation, the mean logMAR BCVA was 0.62±0.17, 0.39±0.18, and 0.34±0.13, respectively. The visual acuity improved significantly after operation compared with before operation, and the difference was statistically significant ( F=119.731, P=0.000). The mean CRT before the operation was 476.0±104.1 μm. At 1, 6, and 12 months after the operation, the average CRT were 299.8±29.9, 272.2±17.8, and 261.0±19.3 μm, respectively. The average CRT after the operation was significantly lower than those before the operation ( F=185.518, P=0.000). At 1, 6, and 12 months after the operation, the mean M values were 0.62±0.54, 0.43±0.41, and 0.32±0.36, respectively; the difference was statistically significant ( F=6.568, P=0.020). After the operation, 48 eyes (84.2%, 48/57) had microstructural abnormalities in the macular area, including EZ and ELM integrity disruption, SRF, CME, and ERM. Correlation analysis showed that M value was significantly positively correlated with BCVA, CRT, and SRF height before operation ( r/ rs=0.672, 0.385, 0.932; P<0.05). There was no correlation between M value and BCVA ( r/ rs=0.503), EZ and ELM integrity ( r/ rs=0.497, 0.472), SRF ( r/ rs=0.416), CME ( r/ rs=0.821) and ERM ( r/ rs=0.632) after operation ( P>0.05). Conclusions:The BCVA is significantly increased and the metamorphopsia is improved after anatomically successful RRD surgery. Postoperative M value is highly correlated with preoperative BCVA, CRT, and SRF.

Purpose: The influence of fasting blood glucose (FBG) and cholesterolemia primary liver cancer (PLC) in china was analyzed via a large prospective cohort study based on a community population, and the combined effects between them were investigated. Materials and Methods: Overall, 98,936 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed up after examination. The correlations of serum FBG or TC with PLC were analyzed. Then, we categorized all staff into four groups: normal FBG/ non-hypocholesterolemia, normal FBG/hypocholesterolemia, elevated FBGon-hypocholesterolemia, elevated FBG/hypocholesterolemia and normal FBG/ non-hypocholesterolemia was used as a control group. The combined effects of elevated FBG and hypocholesterolemia with PLC were analyzed using the Age-scale Cox proportional hazard regression model. Results: During 1,134,843.68 person*years follow up, a total of 388 PLC cases occured. We found the elevated FBG and hypocholesterolemia increases the risk for PLC, respectively. Compared with the non-hypocholesterolemiaormal FBG group, the risk of PLC was significantly increased in the non-hypocholesterolemia/elevated FBG group (HR=1.19,95%CI 0.88–1.62) and hypocholesterolemiaormal FBG group (HR=1.53,95%CI 1.19–1.97), and in the hypocholesterolemia/elevated FBG group (HR=3.16 95%CI2.13-4.69). And, a significant interaction effect was found of FBG and TC on PLC. All results were independent from the influence of liver disease. Conclusion Elevated serum FBG and hypocholesterolemia are risk factors for PLC, especially when combined. Thus, for the prevention and treatment of PLC, serum FBG and TC levels should be investigated.

Objective:To investigate the clinical type and gene mutations, clinical manifestations, laboratory tests, diagnosis, and fibrinogen replacement therapy of congenital fibrinogen disorders.Methods:Clinical data of 146 patients with congenital fibrinogen disorders diagnosed from April 2000 to November 2020 were retrospectively analyzed.Results:Among the 146 patients, 61 (41.8%) men and 85 (58.2%) women had a median age of 33.5 years at the time of consultation. 34 patients (34.7%) were found to suffer from the disease due to bleeding symptoms, 33 patients (33.7%) due to preoperative examination. 55 patients (56.1%) had at least one bleeding symptom, and 42 patients (42.9%) had no bleeding symptoms. There is a negative correlation between fibrinogen activity concentration and bleeding ISTH-BAT score (rs=-0.412, P=0.001) . A total of 34 gene mutations were detected in 56 patients, of which 84.1% were missense mutations, and 16 new mutations were found. FGA Exon2 and FGG Exon8 mutations accounted for 71.4% of all mutation sites. Patients with afibrinogenemia were younger, with a median age of 2 (1-12) years, an ISTH-BAT score of 4, and patients with dysfibrinogenemia had significantly longer thrombin time (TT) , with a median of 28.5 (19.2-36.6) s. The 1 hour in vivo recovery (IVR) after fibrinogen infusion was (127.19±44.03) %, and the 24 hour IVR was (101.78±43.98) %. In addition to the obvious increase in the concentration of fibrinogen activity, the TT and the prothrombin time (PT) both decreased significantly, and the TT decreased more significantly, with an average decrease of 15.2% compared to the baseline after 24 hours of infusion. Conclusion:Most patients with congenital fibrinogen disorders have mild or no bleeding symptoms. Patients with afibrinogenemia have more severe symptoms. There is a negative correlation between the fibrinogen and the degree of bleeding. Genetic testing is helpful for the diagnosis of disease classification. FIB∶C/FIB∶Ag<0.7 can be used as a basis for clinical diagnosis. The TT can be used as the basis for the diagnosis of dysfibrinogenemia and the effectiveness of fibrinogen infusion.