[Expression of DARS2 in colorectal cancer and its clinical significance].

Objective: To investigate the expression of DARS2 and its clinical significance in colorectal cancer. Methods: In this study, bioinformatics tools, especially gene expression profile interactive analysis 2 (GEPIA2), were used to conduct an in-depth analysis of DARS2 expression in colorectal cancer tissues. Immunohistochemical staining was carried out in 108 colorectal cancer specimens and 30 normal colorectal tissues obtained from the First Affiliated Hospital of Nanchang University, Nanchang, China. Colorectal cancer cell lines (HCT116 and SW480) were transfected with small interfering RNA (siRNA) and DARS2 overexpression plasmid to examine the effects of DARS2 knockdown and overexpression on cell function. To assess the effects on cell function, CCK8 and transwell migration assays were used to assess proliferation and cell motility, respectively. Additionally, protein immunoblotting was employed to scrutinize the expression of proteins associated with the epithelial-mesenchymal transition of colorectal cancer cells. Results: DARS2 exhibited a pronounced upregulation in expression within colorectal cancer tissues compared to their normal epithelial counterparts. Furthermore, DARS2 expression was higher in colorectal cancer of stage Ⅲ-Ⅳ than those of stage Ⅰ-Ⅱ, exhibiting a significant correlation with N staging, M staging, and pathological staging (P<0.05). Kaplan-Meier analyses showed a decreased overall survival rate in colorectal cancer with DARS2 expression compared to those without DARS2 expression (P<0.05). In the siRNA transfection group, there was a significant reduction in cell proliferation and migration (P<0.01 and P<0.05, respectively). Conversely, the transfection of DARS2 overexpression plasmids substantially increased both cell proliferation and migration (P<0.05). Additionally, immunoblotting revealed that DARS2 knockdown led to an upregulation of E-cadherin expression and a downregulation of N-cadherin and vimentin expression. In contrast, DARS2 overexpression resulted in increased N-cadherin and vimentin expression, coupled with reduction in E-cadherin expression. Conclusions: There is a strong association between DARS2 expression and colorectal cancer progression. Silencing DARS2 inhibits cell proliferation and migration, exerting a discernible influence on the epithelial-mesenchymal transition process.

[Progress and prospect of clinical application of anti-rabies virus monoclonal antibody preparation].

Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization's position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category Ⅲ exposure for the first time, as well as in category Ⅱ exposure that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine. Therefore, the anti-rabies virus monoclonal antibody preparation shows great potential for clinical application in PEP.

[The application value of metagenomic next-generation sequencing technology in diagnosis and treatment of pulmonary infection in immunocompromised patients].

Objective: To evaluate the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of pulmonary infection in immunocompromised patients. Methods: A total of 78 patients with immunocompromised pulmonary infection [55 males and 23 females, aged (50.3±16.9) years] and 61 patients with non-immunocompromised pulmonary infection [42 males and 19 females, aged (63.6±15.9) years] in the Intensive Care Unit of the First Medical Center of College of the Pulmonary & Critical Care Medicine, Chinese PLA General Hospital from November 2018 to May 2022 were retrospectively selected. Patients in both groups received bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs) while clinically diagnosed with pulmonary infection. The diagnostic positive rate, pathogen detection rate and clinical coincidence rate of the two methods were compared. At the same time, the difference of adjustment rate of anti-infective treatment strategy based on the results of mNGS detection was compared between the two groups. Results: The positive rates of mNGS in patients with pulmonary infection were 94.9% (74/78) and 82.0% (50/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of CMTs in patients with pulmonary infection were 64.1% (50/78) and 75.4% (46/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of mNGS and CMTs in patients with pulmonary infection in immunocompromised group showed a statistically significant difference (P<0.001). The detection rates of mNGS in the immunocompromised group for pneumocystis jirovecii and cytomegalovirus were 41.0% (32/78) and 37.2% (29/78), respectively, and the detection rates of Klebsiella pneumoniae, chlamydia psittaci and Legionella pneumophila were 16.4% (10/61), 9.8% (6/61) and 8.2% (5/61) in the non-immunocompromised patients, respectively, which were higher than those of CMTs [1.3% (1/78), 7.7% (6/78), 4.9% (3/61), 0 and 0] (all P<0.05). In the immunocompromised group, the clinical coincidence rates of mNGS and CMTs and were 89.7% (70/78) and 43.6% (34/78), respectively, with a statistically significant difference (P<0.001). In the non-immunocompromised group, the clinical coincidence rates of mNGS and CMTs were 83.6% (51/61) and 62.3% (38/61), with a statistically significant difference (P=0.008). In the immunocompromised group, according to the results of the etiology of mNGS, the adjustment rate of anti-infection treatment strategy was 87.2% (68/78), while in the non-immunocompromised group, the adjustment rate of anti-infective treatment strategy was 60.7% (37/61), with a statistically significant difference (P<0.001). Conclusion: In patients with immunocompromised pulmonary infection, mNGS has more advantages than CMTs in diagnostic positive rate, diagnosis rate of mixed infection, pathogen detection rate and guidance of anti-infection treatment strategy adjustment, which is worthy of clinical promotion and application.

[Risk factors of pancreatitis after percutaneous transhepatic biliary drainage in patients with pancreatic cancer and obstructive jaundice].

Objective: To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice. Methods: A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode. Results: Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD (P<0.05). Logistic regression analysis showed that visualization of pancreatic duct (OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation (OR=0.14), pancreatic atrophy (OR=0.12) and external drainage (OR=0.11) were protective factors for pancreatitis. Conclusion: In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.

[The construction of comprehensive stroke prevention and control system requires attention to the precise policies of young stroke].

Youth is the core force of social and economic development, once the occurrence of youth stroke will place a heavy burden on society and family. However, the prevention and control of stroke in China is mainly aimed at middle-aged and elderly patients, the part of young stroke is relatively easy to be ignored. This article focuses on the characteristics, research progress, prevention and control status of young stroke, pointing out the importance of centering on the prevention and treatment of young stroke. At the same time, it hopes that the industry can concentrate on the prevention and treatment of young stroke, making precise policies in the future, and developing secondary prevention guidelines for the causes or risk factors of young stroke, so as to improve comprehensive stroke prevention and control system. On this basis, the health level of the whole population will be improved, and the life expectancy of residents will be extended, thus promoting the realization of the strategic goal of "Healthy China 2030".

Comparative genome-wide methylation analysis of longissimus dorsi muscles in Yorkshire and Wannanhua pigs.

DNA methylation was one of the earliest discovered epigenetic modifications in vertebrates, and is an important epigenetic mechanism involved in the expression of genes in many biological processes, including muscle growth and development. Its effects on economically important traits are evidenced in reported differences in meat quality traits between Chinese indigenous pig breeds (Wannanhua pig) and Western commercial pig breeds (Yorkshire pig), and this presents a unique model for analyzing the effects of DNA methylation on these traits. In the present study, a whole genome DNA methylation analysis was performed on the two breeds using methylated DNA immunoprecipitation. GO functional enrichment and pathway enrichment analyses identified differentially methylated genes primarily associated with fatty acid metabolism, biological processes of muscle development and signaling pathways related to muscle development and pork quality. Differentially methylated genes were verified by sodium pyrosequencing, and the results were consistent with the sequencing results. The results of the integrative analysis between DNA methylation and gene expression revealed that the DNA methylation levels showed a significantly negative correlation with gene expression levels around the transcription start site of genes. In total, 41 genes were both differentially expressed and methylated; these genes were related to fat metabolism, lipid metabolism and skeletal muscle development. This study could help further explore the molecular mechanisms and phenotypic differences in pig growth and development among different breeds.

NLRP6-caspase 4 inflammasome activation in response to cariogenic bacterial lipoteichoic acid in human dental pulp inflammation.

AIM: To explore the presence and function of NLRP6-caspase 4 inflammasome in human pulp tissue and human dental pulp cells (HDPCs). METHODOLOGY: Pulp tissue was collected from freshly extracted human caries-free third molars and third molars with irreversible pulpitis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were performed to assess the expression of NLRP6-caspase 4 inflammasome. HDPCs were prepared from normal human pulp tissues and challenged with Porphyromonas gingivalis LPS. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were performed to assess if LPS can upregulate NLRP6 and caspase-4. HDPCs were further challenged with LPS followed with cytosolic Streptococcus mutans lipoteichoic acid (LTA). SiRNA targeting NLRP6 and Casp4 and pharmacology inhibitor Ac-FLTD-CMK and MCC950 were used to assess if Streptococcus mutans LTA can activate the NLRP6 but not the NLRP3 inflammasome. Western blot and ELISA were performed to evaluate inflammasome activation. The Student's t-test and one-way anova were used for statistical analysis. RESULTS: NLRP6-caspase 4 inflammasome was upregulated and activated in inflamed human dental pulp tissue. In HDPCs, Porphyromonas gingivalis LPS upregulated the expression of NLRP6, CASP1 and CASP4 in a type I interferon dependent manner. After LPS priming, cytosolic Streptococcus mutans LTA triggered NLRP6-caspase 4 inflammasome activation. Knockdown of NLRP6 or CASP4 using siRNA or using pharmacology inhibitor Ac-FLTD-CMK but not MCC950 efficiently suppressed inflammasome activation by cytosolic LTA. CONCLUSIONS: NLRP6-caspase 4 inflammasome may play an important role in pulp inflammation and immune defence. Inflammatory caspases represent a pharmacological target to restrain pulpal inflammation.

[The perfection of the law on prevention and treatment of infectious diseases against the backdrop of COVID-19 pandemic].

The COVID-19 pandemic shows the defects of current public health law system and the necessity of the amendment to Law on Prevention and Treatment of Infectious Diseases. The institutional design of the prevention and control of emerging communicable disease shall be modified and Principle of Preventive Legislation shall be determined. Following the multicultural coordination in the pandemic prevention and control, the responsibilities of the central and local government shall be clarified and the functions of the experts and the public need to work fully and effectively. Current pandemic information release system shall be reformed to solve the conflict of laws and the information direct system shall be optimized. Principle of proportionality shall be obeyed to protect the appropriateness, necessity and balance of the pandemic prevention and control measures.

[Establishment and validation of a new predictive equation with multiple risk factors for the development of cardiorenal syndrome type 1 in patients with acute myocardial infarction].

Objective: To investigate the independent risk factors of cardiorenal syndrome type 1 (CRS1) in patients with acute myocardial infarction (AMI) and to build a predictive equation for the development of CRS1 in these patients. Method: Consecutive inpatients with AMI, who hospitalized from January 2017 to December 2018 in the Hunan Provincial People's Hospital, were enrolled in this case-control study. Patients were divided into CRS1 group and non-CRS1 group according to the presence or absence of CRS1.The clinical data were collected through the electronic medical record system of Hunan Provincial People's Hospital. The matching process was conducted with a minimum-distance scoring method and a 1∶1 match between the CRS1 group and the no-CRS1 group, the propensity score was calculated through the logistic regression model. Factors with statistically significant differences in univariate analysis were included in the multivariate logistic regression model to analyze the risk factors of AMI patients with CRS1, then the independent risk factors were used to establish a predicting equation for CRS1 by logistic regression function for model building. Area under the curve (AUC) value and the best cut-off value of the combined predictors was determined according to the ROC curve. Python 3.8 software was used to perform 10-fold cross-validation on modeling samples. Results: A total of 942 patients were included, there were 113 cases in CRS1 group and 829 cases in non-CRS1 group. Ultimately, 99 CRS1 patients were successfully matched to 99 non-CRS1 patient using 1∶1 matching. After propensity score matching, the baseline age and sex along with heart rate, mean arterial pressure, percentage of people with a history of diabetes, hypertension, ST-segment elevation myocardial infarction, myocardial ischemia time, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers use, and ß receptor blocker use were similar between the two groups(all P>0.05). The contrast agent dosage was also similar between the two groups (P=0.266). The peak cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), white blood cell count, base estimated glomerular filtration rate (eGFR), albumin and hemoglobin levels were statistically significant between the two groups (all P<0.05). Multivariate logistic regression analysis showed that decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count were independent risk factors of CRS1 in AMI patients (all P<0.01).The predicting equation of the combined predictor was established by transforming the logistic model equation, L=0.031×cTnI+0.000 2×NT-proBNP-0.024×eGFR+0.254×white blood cell count, where L represented the combined predictor. ROC curve analysis indicated that the AUC of the peak cTnI, NT-proBNP, baseline eGFR, white blood cell count, and combined predictor were 0.76, 0.85, 0.79, 0.81, and 0.92 respectively (all P<0.05), and the cutoff value of combined predictor was 2.6. The AUC of ROC curve after the model's ten-fold cross validation was 0.89. Conclusions: Decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count are the independent risk factors for CRS1 in AMI patients. The combined predictor equation based on the above 4 biomarkers presents a good predictive value for CRS1 in AMI patients.

[Application of multidisciplinary team (MDT) in the treatment of severe trauma].

OBJECTIVE: To explore the effect of multi-disciplinary team (MDT) in general hospitals on severe trauma patients. METHODS: This study reviewed the treatment of patients with severe trauma in trauma center of Peking University People's Hospital from March 2017 to April 2019. The baseline information: the patients' gender, age, injury mechanism, etc.; the start indicators: the Glasgow coma scale (GCS), trauma index (TI), injury severity score (ISS); the start related indicators: time for activation, time for MDT to arrive, time for CT scan, time for damage control surgery; patient treatment and prognosis: ICU (intensive care unit) length of stay, number of cured and discharged patients, number of dead cases, number of patients transferred to rehabilitation hospital, were all analyzed. It discussed the composition of MDT, the initiation scheme, the indicators of initiation of MDT for severe trauma, and analyzed the correlation between the application of MDT and the prognosis of patients. RESULTS: From March 2017 to April 2019, 112 trauma patients were treated by MDT in Peking University People's Hospital. There were 69 males and 43 females. The minimum age was 15 years, the maximum age was 89 years, most of them were 36-55 years old. The main injury mechanism was traffic accident injury. The GCS, TI, ISS were 13.0±2.9, 13.0±2.8, and 21.5±11.9, respectively. It took 3.7±0.8 minutes to start the call, 6.1±0.9 minutes for MDT personnel to arrive at the emergency rescue area, 23.8±3.0 minutes for fast CT and 92.6±15.4 minutes for injury control operation. All the hospitalized patients were treated effectively. ICU (Intensive care unit) hospitalization time was 12.6±6.7 days. 55 discharged patients were cured, 5 died (1 died of hemorrhagic shock, 4 died of severe brain injury) and 52 transferred to rehabilitation hospital. CONCLUSION: The treatment of severe trauma patients by MDT in trauma center of general hospitals can greatly improve the ability and level of treatment of severe trauma patients, make up for the lack of treatment of severe trauma especially multiple trauma patients in large general hospitals, and improve the treatment effect of severe trauma patients. It provides a reference model for large general hospitals to treat patients with severe trauma and multiple trauma and for the construction of trauma centers.

[Closed percutaneous reduction and minimally invasive treatment of spastic hammery deformity].

Objective: To investigate the efficacy of percutaneous extensor tendon reconstruction in treating spastic hammery deformity. Methods: From February 2009 to July 2018, the clinicaldata of 36 patients with fresh sputum hammer fingers treated in Jinan People's Hospital were analyzed retrospectively. The tendon was percutaneously sutured with PDS Ⅱmonofilament suture and the distal end of the tendon was fixed to the base of the distal phalanx through the bone hole. Removal of the K-wire 6 weeks after the operation, the brace was used to fix the affected finger in the dorsal extension. For 8-10 weeks, only the brace was worn at night and the flexion and extension of the affected finger was gradually strengthened.The extension and flexion function of the interphalangeal joint of the finger was compared pre and post the operation with t test. Results: A total of 36 patients were enrolled but only 33 patientswere followed up for 6 to 15 months. The hammer-shaped deformity was corrected and there was no pain when moving fingers after the operation.The straightening angle of the interphalangeal joint of the finger improved from 46.2°±6.3° before surgery to 7.5°±0.6° after (t=35.12, P<0.05). The passive straightening angle decreased from 3.2°±0.3° before surgery to 0.9°±0.2° after (t=37.11, P<0.05). According to the Crawford functional assessment: excellent in 19 fingers, good in 10 fingers, can be in 4 fingers. The excellent rate was 87.9%. There was no knot exposure, skin necrosis and other complications. Conclusions: Percutaneous resection of the extensor tendon is fixed in the basal phalanx. It is a simple and feasible minimally invasive surgery for hammer-shaped deformity. It can obviously correct the hammer-shaped deformity and has fewer complications.

[Clinical features and prognostic factors of parainfluenza virus infections in adult patients].

Objective: To explore the clinical features and prognostic factors of parainfluenza viral lower respiratory tract infections in adults. Methods: A total of 70 patients withpositive nucleic acid of parainfluenza virus (PIV) admitted to China-Japan Friendship Hospital between August 2016 and November 2019 were enrolled. Multiplex real-time polymerase chain reaction (RT-PCR) assays for viral detection were implemented to specimens (nasopharynx swab, sputum or bronchoalveolar lavage) obtained from all the patients, which was consistent with the diagnosis of lower respiratory tract infection. Patients were divided into two groups depending on the status of immune function (immunocompromised group, n=26; immunocompetent group, n=44), and patients were divided into PIV infection group (n=43) and mixed infection group (n=27) according to whether there was mixed infection. Characteristics including age, gender, underlying diseases, symptoms, disease severity, imaging manifestations, etiology, respiratory failure, mechanical ventilation, vasoactive drug, antimicrobial drug and 30-day mortality between the groups were compared, and the prognostic factors of PIV infections were investigated using Cox regression. Results: The peak incidence of PIV infection time was in May, August, September and December, accounting for 58.6% of all cases. The enrolled 70 cases included 43 cases with pneumonia, 16 cases with interstitial lung disease and infection, 7 cases with bronchiectasis and infection, and 4 cases with acute exacerbation of chronic obstructive pulmonary disease. Eight patients (11.4%) had no underlying diseases, 21 patients (30.0%) had respiratory failure, 18 patients (25.7%) were treated with mechanical ventilation, 15 patients (21.4%) died within 30 days after admission. The pneumonia severity index score, percentage of patients with ground-glass opacity according CT scan, with honeycomb or reticular pattern, with mechanical ventilation, with respiratory failure, with ICU admission, and 30-day mortality in immunocompromised group were higher than those of immunocompetent group [(91.5 vs 84.0), (60.0% vs 34.1%), (44.0% vs 11.4%), (42.3% vs 15.9%), (50.0% vs 18.2%), (38.5% vs 22.7%), (34.6% vs 13.6%)] (all P<0.05). There were 27 cases (38.6%) with mixed infection, including 17 viruses (24.3%), 19 bacteria (27.1%), 14 (20.0%) fungi (PCP, aspergillus) and 1 (1.4%) Mycobacterium intracellulare. Sixteen patients (59.3%) in the mixed infection group were immunocompromised patients and 21 patients (77.8%) had chronic lung disease. Cox regression analysis showed that mechanical ventilation and interstitial lung disease were independent predictors of prognosis in all patients, and mechanical ventilation was an independent predictor of prognosis in PIV infection group. Conclusions: Most of the patients with PIV lower respiratory tract infection in adults are complicated with underlying diseases and mixed infection, with a high 30-day mortality. Interstitial lung disease and mechanical ventilation indicate poor prognosis in these patients.

[Classification and production process of human vaccine].

Human vaccine is the most effective tool to prevent infectious diseases. At present, there are dozens of vaccines that can prevent dozens of infectious diseases. Vaccines for human use include vaccines that do not contain living micro-organisms (inactivated vaccines, toxoid vaccines, component vaccines), and vaccines that contain living micro-organisms (live attenuated vaccines and vector vaccines). The research and development of human vaccine includes clinical trial, process development and test method research, and the production process of human vaccine is very important for the preparation of high-quality and reliable vaccine. In this paper, the development of human vaccines, the production process and the characteristics of various human vaccines are reviewed.

[Research progress of tetanus antibody detection technology in China].

The situation of prevention of non-neonatal tetanus in China is severe. Strengthening the active immunization with tetanus toxoid vaccine (TTCV) is the key to prevent the non-neonatal tetanus. Through the detection of tetanus antibody (TAB), the immune status of individual can be determined, so as to implement the active immunization of TTCV correctly. The research on TAB detection technology is stagnant in aboard, but still in a development process in China since there is a realistic demand for TAB detection. This review collects relatively limited data of TAB detection technology in China, and summarizes the techniques such as mice toxin neutralization test (MTNT), indirect hemagglutination assay (IHA), double agar gel immune diffusion test (Rubin method), enzyme-linked immunosorbent assay (ELISA) and colloidal gold (CG), in order to provide a comprehensive basis for domestic TAB detection. The TAB detection technology in China has not yet achieved international recognition due to the lack of comparative study of domestic and international institutions and reference reagents. The special domestic situation of tetanus prevention makes the research of TAB detection technology have a certain practical significance, and rapid detection reagents such as ELISA and CG method have a certain application value in China.

[Meta-analysis on tetanus antibody protection rate of healthy population born after 1978 in China].

Objective: Meta-analysis was conducted on the tetanus antibody protection rate of healthy population born after 1978 in China (data from Hong Kong, Macao and Taiwan was excluded, the same below). Methods: Search the data on China's tetanus antibody level which were published in China National Knowledge Infrastructure, Wanfang data, VIP, SinoMed database, PubMed and the Cochrane Library. The Chinese search keywords were "Tetanus Antitoxin", "Tetanus Antibody", "Healthy Population" and "Mainland China". English search terms include "tetanus antitoxin", "tetanus vaccine", "tetanus vaccine", "general population" and "mainland of China". The time limit for inclusion in literature research was 2010-2019. Stata software was used to conduct meta-analysis on the protection rate of tetanus antibody. Results: A total of 24 articles were included. There was no obvious publication bias in the included articles. The total number of respondents was 23 530, the antibody protection rate was 49.5%-99.0%. A total of 20 817 people got effective antibody protection, which meant the antibody level reached and exceeded 0.1 IU/ml, and the combined protection rate was 78.6% (95%CI: 75.0%-88.2%). The combined protection rates of antibody in 0-7 years old and 8-15 years old groups were 88.9% (95%CI: 86.9%-91.0%) and 79.3% (95%CI: 72.9%-86.2%) respectively. The combined protection rates of antibodies in 16-20 years old, 21-30 years old and 31-40 years old groups were 58.9% (95%CI: 46.5%-71.2%), 47.7% (95%CI: 16.8%-78.7%) and 63.8% (95%CI:32.6%-95.1%) respectively. The combined protection rate of tetanus antibody for 0-15 years old people was 85.6% (95%CI: 83.1%-88.1%), and the combined protection rate of antibody for 16-40 years old people was 52.9% (95%CI: 39.3%-66.6%). Conclusion: With the increase of age, the protection rate of tetanus antibody among the healthy population aged 16-40 years in our country decreases. An individualized vaccination plan should be formulated according to the previous tetanus vaccination history and the tetanus antibody level when necessary.

[Pathological characteristics and molecular diagnosis of non-tuberculosis Mycobacterium lung disease].

Objective: To investigate the clinicopathological features of non-tuberculosis mycobacterial lung disease and the role of molecular pathology in diagnosis. Methods: Forty-five formalin-fixed, paraffin embedded (FFPE) specimens were collected from the Department of Pathology, Beijing Chest Hospital from February 2016 to August 2019. The clinical, imaging and histopathologic features, bacteriologic data and morphologic characteristics of acid fast bacilli (AFB) were analyzed retrospectively. Specific gene sequence IS6110 of Mycobacterium tuberculosis (MTB) was detected by fluorescence PCR. Identification of Mycobacteria was by melting curve method. Fifty cases of pulmonary tuberculosis were selected in the same period as control. Results: The NTM lung cases included 18 cases (40.0%, 18/45) of M. intracellulare, eight cases (17.8%, 8/45) of M. xenopi, six cases (13.3%, 6/45) of M. avium, six cases (13.3%, 6/45) of M. kansasii, six cases (13.3%, 6/45) of M. chelonae and one case (2.2%, 1/45) of M. simiae. Histopathologically, there were necrotizing granulomas in 34 cases (75.6%, 34/45), non-necrotizing granuloma in one case (2.2%, 1/45) and non-granulomatous lesions in 10 cases (22.2%, 10/45). The necrosis was pink necrosis, basophilic necrosis rich in nuclear fragments and suppurative necrosis. Pulmonary TB showed more pink necrosis and basophilic necrosis, the difference was statistically significant (χ(2)=10.270, P=0.001; χ(2)=7.449, P=0.006). Seventeen cases (37.8%, 17/45) of NTM lung disease showed giant multinucleated giant cells, which were significantly different from those in pulmonary tuberculosis group (χ(2)=13.446, P<0.01). The number and morphology of AFB were also different. More AFB were found in M. intracellular cases and significant AFB were easily seen in M. kansasii infection. Conclusions: M. tuberculosis and NTM cannot be reliably differentiated by histologic features or by AFB morphology. Molecular assays are important to distinguish tuberculosis from NTM lung disease.

[Phenotype and genotype analysis of 55 children patients with Wilson's disease].

Objective: To understand the clinical phenotype and spectrum of ATP7B gene mutation in children with Wilson's disease (WD). Methods: A total of 55 cases diagnosed with WD at the Children's Hospital Affiliated to Nanjing Medical University from June 2012 to June 2018 were taken as the research subject. ATP7B gene point mutation was detected by direct sequencing after PCR amplification. Heterozygous mutation in children was discovered by sequencing. Furthermore, the long segment mutation of exon was analyzed by multiplex ligation-dependent probe amplification (MLPA). Results: All 55 WD children had varying degree of liver damage symptoms. Among them, 2 cases had combined neurological symptoms. The positive rates of K-F ring (21%), 24-hour urine copper (97.7%), and ceruloplasmin were all abnormal. The results of ATP7B gene had identified 8 homozygous, 41 compound heterozygous and 6 heterozygous in 55 cases. Direct sequencing method had detected ten cases of ATP7B heterozygotes. In addition, MLPA analysis showed that other allele in four cases had a deletion of the ATP7B gene exon. In all cases, 35 different ATP7B gene mutations were detected, including 23 missense mutations, 3 frameshift mutations, 4 nonsense mutations, 3 exon deletions and 2 splicing changes. The most common allele mutation was c.2333G > T/p.R778L in exon 8, with an allele frequency of 36.54%, followed by c.2975C > T/p.P992L in exon 13, with an allele frequency of 14.42%. Conclusion: ATP7B gene c.2333G > T/p.R778L and c.2975C > T/p.P992L mutations are the most common mutations in children with WD in China. WD patients report shows that there are three long deletion mutations in the exon of the ATP7B gene. For WD children whose DNA sequencing is heterozygous ATP7B gene, it is suggested to further use MLPA method to detect deletion mutations of exons.

Biological background of the genomic variations of cf-DNA in healthy individuals.

BACKGROUND: Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA remains challenging, partially because of the undefined biological background of cf-DNA. MATERIALS AND METHODS: We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 × 10-7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA. RESULTS: Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely 'passenger mutations' of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors. CONCLUSION: Hematopoietic clone-derived mutations, including 'driver mutations' and 'passenger mutations', are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.

Reconfigurable sensor and nanoantenna by graphene-tuned Fano resonance.

With the rapid developments in compact devices, the multi-function and reconfigurability of nanostructures are highly appreciated, while still very challenging. A majority of devices are usually mono-functional or hard to switch between different functions in one design. In this paper, we proposed graphene-wrapped core-shell nanowires to realize real-time reconfigurable sensors and nanoantenna by tuning the Fermi energies of graphene layers at the surfaces of core and shell, respectively. Owing to the electromagnetic coupling between the two graphene layer, two corresponding Fano resonances of scattering can arise in the Terahertz spectrum, which arises from the interference of bright modes and dark modes. Around the Fano resonances, the scattering can be considerably resonant (as an antenna) or suppressed (as a sensor). Interestingly, the field distributions are distinct at the suppressed scattering states for the two Fano resonances. The presented reconfigurable nanostructures may offer promising potentials for integrated and multi-functional electromagnetic control such as dynamic sensing and emission.

A first-principles study on magnetic properties of the intrinsic defects in wurtzite ZnO.

Since the origin of magnetism in ZnO-based diluted magnetic semiconductors (DMSs) is still controversial, in this work, we presented a detailed study on the magnetic, structural, and electronic properties of wurtzite ZnO-based DMS systems with point and complex intrinsic defects. Two outer electrons from neutral oxygen vacancy (VO) occupy the a1 orbital, making the inducted magnetic moment to be zero, while a cluster including three VOs leads to a magnetic moment of ∼1 µB. The magnetic moment of the system with a Zn vacancy (VZn) is 1.65 µB. When two neutral VZns in different relative distances were created in respective supercells, the systems showed different magnetic moments induced by the unequal level between the highest electron occupied orbital of the defect state introduced by different VZn sites and the valence band maximum. The system of a neutral O occupying an octahedral site gives rise to a magnetic moment of 2 µB, while zinc interstitial and antisite defects do not cause spin polarization. The system with a complex defect of VO and VZn is magnetic when those vacancies are adjacent but still do not cause the compensation effect. The oxygen interstitial defect is unstable, and VZn easily turns into the complex defect. We suggest that VO clusters and VZn complex defects could likely be the origin of ferromagnetism in undoped ZnO.