A study on repair method of type Ⅱc injury in lateral meniscus popliteal tendon area of porcine knee / 中国修复重建外科杂志

OBJECTIVE@#To investigate the repair method of type Ⅱc injury in the lateral meniscus popliteal tendon area based on the porcine knee joint.@*METHODS@#Eighteen commercially available fresh porcine knee joints were randomly divided into 3 groups ( n=6). After preparing a type Ⅱc injury in the lateral meniscus popliteal tendon area, and the anterior (group A), posterior (group B), or anterior and posterior (group C) of the popliteal hiatus (PH) was sutured by vertical mattress. The tension meter was used to apply gradient tensions of 2, 4, 6, 8, and 10 N along the tibial plateau horizontally, respectively, to pull the midpoint of the lateral meniscus popliteal tendon area. The displacement values before modeling, after modeling, and after suture were recorded. The reduction value of lateral meniscus displacement and reduction rate after suture were calculated and compared between groups.@*RESULTS@#There was no significant difference between groups ( P>0.05) in the displacement values before modeling, after modeling, and after suture under different tensions. There was no significant difference between groups A and C ( P>0.05) in the reduction value of lateral meniscus displacement and reduction rate after suture under different tensions. The reduction value of lateral meniscus displacement and reduction rate after suture in group B were lower than those in groups A and C. The reduction value of lateral meniscus displacement under tension of 2 N and the reduction rates under tensions of 2, 4, and 6 N between groups A and B showed significant differences ( P<0.05). The reduction value of lateral meniscus displacement and the reduction rate under tensions of 2, 4, and 6 N between groups B and C showed significant differences ( P<0.05).@*CONCLUSION@#Suturing the anterior area of PH is the key to repairing type Ⅱc injury of lateral meniscus popliteal tendon area.

Genetic background of idiopathic neurodevelopmental delay patients with significant brain deviation volume / 中华医学杂志(英文版)

BACKGROUND@#Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV).@*METHODS@#We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.@*RESULTS@#We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.@*CONCLUSION@#Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.

Point-of-care testing technology and experimental diagnosis of insect-borne diseases: applications and challenges / 中华检验医学杂志

Insect-borne infections are causing serious public health concerns worldwide. Point-of-care testing technology for insect-borne diseases can rapidly and accurately determine the pathogens, thus it plays an important role in the application of portable disease control measurements. This article provides an overview of the point-of-care testing technology for insect-borne infectious diseases regarding its application, advantages and limitations in experimental diagnoses, and its future trends.

Correlation between early inflammation indicators and the severity of coronavirus disease 2019 / 中华危重病急救医学

Objective:To explore the correlation between early inflammation indicators and the severity of coronavirus disease 2019 (COVID-19).Methods:A retrospective study was conducted. Patients with COVID-19 admitted to Wenzhou Central Hospital from January 17 to February 14, 2020 were enrolled. The general information, chest CT before admission, the first laboratory parameters and chest CT within 24 hours after admission were collected. Patients were followed up for 30 days after the first onset of dyspnea or pulmonary imaging showed that the lesions progressed more than 50% within 24 to 48 hours (according to the criteria for severe cases) as the study endpoint. According to the endpoint, the patients were divided into two groups: mild type/common type group and severe/critical group, and the differences in general information and inflammation index of the two groups were compared. Logistic regression was used to analyze the inflammation index and the severity of COVID-19. Receiver operating characteristic (ROC) curve was draw to evaluate the predictive value of early inflammation indicators for severe/critical in patients with COVID-19.Results:A total of 140 patients with COVID-19 were included, 74 males and 66 females; the average age was (45±14) years old; 6 cases (4.3%) of mild type, 107 cases (76.4%) of common type, and 22 cases (15.7%) of severe type, 5 cases (3.6%) were critical. There were significantly differences in ages (years old: 43±13 vs. 57±13), the proportion of patients with one chronic disease (17.7% vs. 55.6%), C-reactive protein [CRP (mg/L): 7.3 (2.3, 21.0) vs. 40.1 (18.8, 62.6)], lymphocyte count [LYM (×10 9/L): 1.3 (1.0, 1.8) vs. 0.8 (0.7, 1.1)], the neutrophil/lymphocyte ratio [NLR: 2.1 (1.6, 3.0) vs. 3.1 (2.2, 8.8)] and multilobularinltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension and age [MuLBSTA score: 5.0 (3.0, 5.0) vs. 5.0 (5.0, 7.0)] between mild/common group and severe/critical group (all P < 0.05). Univariate Logistic regression analysis showed that CRP, NLR, MuLBSTA score, age, and whether chronic diseases were associated with the severity of COVID-19 [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.037 (1.020-1.055), 1.374 (1.123-1.680), 1.574 (1.296-1.911), 1.082 (1.042-1.125), 6.393 (2.551-16.023), respectively, all P < 0.01]. Further multivariate Logistic regression analysis showed that CRP and MuLBSTA score were risk factors for the development of COVID-19 to severe/critical cases [OR and 95% CI were 1.024 (1.002-1.048) and 1.321 (1.027-1.699) respectively, both P < 0.05]. ROC curve analysis showed that the area under the curve for CRP and MuLBSTA score to predict severe/critical cases were both 0.818, and the best cut-off points were 27.4 mg/L and 6.0 points, respectively. Conclusion:CRP and MuLBSTA score are related to the severity of COVID-19, and may have good independent predictive ability for the development of severe/critical illness.

An investigation on the role of emergency departments in combatting against COVID-19 in Zhejiang Province / 中华急诊医学杂志

Objective:To investigate the relevant situation of the emergency departments (ED) of general hospitals at all levels in Zhejiang Province participating in the prevention and control of Corona Virus Disease 2019 (COVID-19), and to provide a reference for further improving the capacity of emergency services.Methods:A multi-center cross-sectional investigation study was jointly initiated by the Zhejiang Provincial Emergency Medicine Quality Control Center, the Emergency Medicine Branch of Zhejiang Medical Association, and the Emergency Physicians Branch of Zhejiang Medical Doctors Association. Before investigation, experts were organized to develop a special questionnaire. Then the ED of general people's hospitals or Chinese Medicine hospitals at the county/district-level or above were included and their participations in the prevention and control of COVID-19 epidemic between March 9, 2020 and March 15, 2020 were investigated. The collected information included: basic information of the hospitals; participation of ED in fever clinics; the number of COVID-19 patients admitted to ED; the situation of ED support to the anti-epidemic front-line; and the epidemic prevention facilities of ED, and the early supply of medical protective equipments.Results:A total of 181 hospitals from 11 prefectures and cities across the province were finally included, including 52 (28.7%) Grade-A tertiary hospitals, 45 (24.9%) Grade-B tertiary hospitals, 64(35.4%) Grade-A secondary hospitals, and 20 (11.0%) Grade-B secondary or lower hospitals. Among them, 93 (51.4%) were COVID-19 designated hospitals, and 49 (27.1%) had the ability to detect COVID-19 nucleic acid; 177 (97.8%) set up independent fever clinics and 33 (18.6%) were managed by ED alone or mainly. The medical staffs of 65 (36.7%) fever clinics were all or mainly from ED. A total of 213 cases of COVID-19 were received/treated in 40.3% ED, accounting for 17.3% of the total number of cases in Zhejiang Province. A total of 3 848 doctors and nurses supported the front-line of epidemic prevention, of them, 253 supported Hubei Province (accounting for 12.5% ??of the total number). There were 68.5% and 76.8% ED having spare separate clinic and ordinary rescue single room to deal with the COVID-19. In addition, at the early days of anti-epidemic, more than 50% ED were in short supply or even had no medical protective equipment.Conclusions:The ED of Zhejiang Province plays an important role and has made a great contribution to the prevention and control of the COVID-19 epidemic. It is necessary to improve the conditions of ED to effectively respond to the prevention and control of daily infectious diseases.

Effective gene editing by high-fidelity base editor 2 in mouse zygotes

Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease-causing mutations in patients. However, problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical application of such approaches. Recently, a base editor (BE) system built on cytidine (C) deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine (T) efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified high-fidelity version of base editor 2 (HF2-BE2), and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.

Analysis of related detections before blood transfusion in tumor patients / 国际检验医学杂志

Objective To investigate the detection situation and distribution of blood typing positive and negative disagree and irregular antibody positive in blood transfusion related tests in tumor patients ,and to make comparative analysis with the data of non‐tumor patients .Methods The results data in 16 760 patients with blood preparation in our hospital from November 2011 to June 2015 were selected and divided into the tumor patients group and the non‐tumor patients group .Among them ,the results of blood typing positive and negative disagree and positive in the irregular antibody screening test were statistically analyzed .Results 27 cases were ABO blood type positive typing inconsistent with reverse typing ,the occurrence rate of the tumor patients group was 0 .65% ,which of the non‐tumor patients group was 0 .08% ;the irregular antibody positive was in 49 cases ,in which 18 cases were in the tumor patients group with the occurrence rate of 0 .74% ,31 cases were in the non‐tumor patients group witht e occurrence rate of 0 .22% ,showing that the occurrence proportion of blood typing positive and reverse inconsistency and irregular antigen posi‐tive was higher than that of the non‐tumor patients group ,the difference was statistically significant (P<0 .05) ,31 cases in the non‐cancer group ,the positive rate is 0 .22% .18 cases in cancer‐group with 0 .74% incidence rate .It shows that the proportion of posi‐tive in cancer patients was higher than non‐cancer patients (P<0 .05) .The main influencing factors affecting blood typing problems in the tumor patients group and non‐tumor patients group were the antibody weakening ,followed by autoantibody ,etc .the reasons for the irregular antibody screening positive in the two groups were mainly the specific antibodies .Conclusion The disease charac‐teristics of tumor patients are easier to cause ABO blood type positive and reverse inconsistency and irregular antibody screening positive .In the work ,more attention should be paid to the detection results for avoiding the missed detection ,increasing the identifi‐cation ability and ensuring the blood transfusion safety .determination is more often in cancer patients about Tests about blood transfusion ;This should be relate to character of phymatosis .Much concern should be given to related test of cancer patients′blood transfusion ,avoiding omissions ,and improve the safety of blood infusion .

The effect of Kaolin and propranolol on expression level of matrix metalloproteinase-9 in lung of paraquat intoxicated mice / 中国中西医结合急救杂志

Objective To explore the effect of Kaolin combined with propranolol on matrix metalloproteinase-9 (MMP-9) in lungs of paraquate (PQ) intoxicated mice and the mechanism of protection for lung injury. Methods Fifty-four ICR mice were randomly divided into three groups, 18 mice in each group: namely control group, PQ intoxicated group and treatment group. The PQ intoxicated model was replicated by intra-gastric administration (ig) of PQ 100 mg/kg; after intoxication, 48 g/kg Kaolin combined with 3.2 mg/kg propranolol intra-gastric administration was immediately given to the treatment group, while in the control group, the same volume of normal saline ig was applied. All the mice were sacrificed at 6, 12 and 24 hours after disposal, and the lung was harvested to test the protein expression level of MMP-9 by Western Blot, and the lung tissue pathological changes were observed.Results There was no statistical significance in the protein expression levels of MMP-9 among the control group, PQ intoxicated group and treatment group at 6 hours after disposal (grey value: 0.655±0.045, 0.656±0.045, 0.641±0.036). The protein expression levels of MMP-9 in PQ intoxicated group were increased significantly compared with those in the control group at 12 hours and 24 hours after disposal (12 hours: 0.824±0.039 vs. 0.634±0.038, 24 hours: 0.742±0.039 vs. 0.658±0.041, bothP < 0.05), while the levels of treatment group were significantly lower than those in the intoxicated group (12 hours: 0.760±0.050 vs. 0.824±0.039, 24 hours: 0.686±0.041 vs. 0.742±0.039, bothP < 0.05). In PQ intoxicated group, early capillary dilation and congestion in lung tissue, a large number of inflammatory cells infiltration with mainly neutrophils in alveolar cavity and a small number of red blood cells exudation were seen at 12 hours; at 24 hours, capillary dilation at alveolar walls, congestion, swelling of endothelial cells, small flakes or large patches of inflammatory cell infiltration with mainly neutrophils in lungs were found. In the treatment group, the lung inflammatory cells infiltration, alveolar capillary dilatation, congestion, swelling of the endothelial cells, etc were also visible, but the degree of severity was significantly milder than those in the intoxicated group.Conclusion The interference of Kaolin combined with propranolol can significantly decrease the protein expression level of MMP-9 in lung tissue of acute paraquat poisoned mice that is possibly one of the mechanisms for prevention and treatment of lung injury in paraquat poisoning.

CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.

Study of clinical blood management mode for regional medical center / 国际检验医学杂志

Objective To explore the management mode of regional clinical blood ,as well as the role of Regional Medical Center in the blood management ,and have a comprehensive understanding of Daxing district clinical blood using present situation .Methods Organized Daxing district clinical blood using quality control center experts to do a research of 18 medical institutions in the blood management status of clinical blood demand within the jurisdiction ,and analyzed the statistics related to clinical use of blood in vari‐ous medical institutions from January to December in 2014 ,according to Beijing Wei Yi [2008]189 words in medical institutions of Beijing City ,the department of transfusion(blood bank) in the relevant provisions of the basic standard.Results Through the sur‐vey ,only regional medical center established the department of transfusion in 18 medical institutions ,other medical institutions have set up blood bank .Practitioners of department of transfusion (blood bank) in the number full‐time staff ,with post qualification num‐ber and degree of structure ,difference between regional medical center and other kind hospitals was significant (P0 .05) .Three grade hospitals in biological safety and continuous im‐provement of quality ,could be carried out in accordance with the PDCA cycle ,and have obvious advantages compared with the other one or two grade hospitals .Conclusion Fifteen medical institutions do not have the clinical blood transfusion compatibility testing conditions .To ensure the safety of blood for clinical use ,blood need to be tested by the department of transfusion regional medical center .

Effects of hyperbaric oxygen on the activation of β-catenin in hypoxic ischemic neonate rats / 中华物理医学与康复杂志

Objective To explore the relationship between the proliferation of neural stem cells (NSCs)and the expression of β-catenin protein in neonate rats with hypoxic ischemic brain damage (HIBD) after hyperbaric oxygen (HBO) therapy. Methods One hundred and eighty Sprague-Dawley rats aged 7 days were randomly divided into a normal control group (CON) , a HIBD model group and a HBO treatment group. The HIBD model was induced using Rice's method. Beginning 3h after the HIBD, HBO was administered to the HBO treatment group at 2 atmospheres for 60 min, once daily for 7 days. The HIBD model group was not given any treatment. The expression of nestin/β-catenin protein in the subventricular zone of the ischemic brain was double-stained for immunofluorescence and analyzed by confocal scanning microscopy dynamically at 3 hours, 21 hours, and then on the 3rd, 5th, 7th and 14th day of HBO therapy. The expression of whole cell β-catenin and nuclear β-catenin protein in the left brain were also examined by Western blotting at these 6 time points. Linear correlation was used to analyze the correlation between β-catenin and nestin protein. Results The expression of β-catenin protein in NSCs increased initially at the 21st hour after HBO therapy in the model group and the HBO group as compared with the normal control group.β-catenin protein in the model group reached a higher level, though there was no significant difference between model group and the HBO group. At the 5th day of HBO therapy β-catenin protein in the HBO group had reached a significantly higher level than in the model group. At the 14th day the average expression of β-catenin in the HBO group began to decrease. The expression of nestin protein began to increase 21 hours after HBO therapy began, and it peaked at the 7th day of HBO therapy and then decreased. In the HBO group the increase in nestin protein was linearly correlated with that of β-catenin protein. The whole cell β-catenin protein and β-catenin nucleic protein readings increased initially by the 21st hour of HBO therapy and by the 5th day were significantly higher than the levels in the model group. Conclusion HBO treatment is capable of stimulating the proliferation of NSCs in HIBD neonate rats.The proliferation of NSCs is correlated with the activation of β-catenin protein.

The effect on succinate dehydrogenase of mitochondria in myocardium and liver in sepsis rats treated with edaravone / 中国医师杂志

Objective To observe the effect on succinate dehydrogenase (SDH) of mitochondria in myocardium and liver in sepsis rats treated with edaravone. Methods 30 Sprague-Dawley rats were divided into 3 groups: sham operated group ( group A ), controlled operated group ( group B ), treated group with edaravone (group C). The model of sepsis rats was made by the way of caecum ligated and punctured and 20mg/kg lactate levofloxacin was subcutaneously injected (sci) 15min before and 3h after operation in three group. 5mg/kg edaravone were sci 15min before and 3h after operation in group C. Liver and myocardium were taken from all of them 18h after operation. The activities of SDH in myocardial and hepatic mitochondria were detected, pathological change of mitochondria in liver and myocardium were observed. Results The activities of SDH in myocardial and hepatic mitochondria in group B [ (0. 21 ± 0. 07 ) U/mgprot, (0. 23± 0. 08 ) U/mgprot ] were significantly decreased compared with group A [ ( 0. 33 ± 0. 10 ) U/mgprot, ( 0. 38±0. 12)U/mgprot]. The activities of those in group C[ (0.31 ±0. 08) U/mgprot, (0. 36 ±0. 11)U/mgprot] were significantly increased than group B. Myocardial and hepatic mitochondria swelling and endocytoplasmic reticulum expanding were found in group B by electron microscope, while it showed normal in group C. Conclusion Hepatic and myocardial mitochondrial structure were destroyed and activities of SDH were decreased in sepsis rats. They could be effectively protected by edaravone.