Objective To observe the dynamic changes in matrix metalloproteinase-12(MMP-12) expression during the course of development of radiation pulmonary injuries in order to get an insight of the roles played by MMP-12 during early tissue remodeling after radiation pulmonary injuries.Methods Twenty-four Wistar rats were randomly assigned into four groups(6 each): normal control group and 1,2 and 4 weeks after irradiation groups.The rats in the last three groups received irradiation of the whole lung with 20Gy of 60Co ?-ray,and they were sacrificed 1,2 and 4 weeks post irradiation.The gene expression of MMP-12 was determined by RT-PCR;the protein expression was detected by Western blot;MMP-12 activity was examined by gelatin zymography;the tissue distribution of MMP-12 was observed by immunohistochemistry;the degradation and collapse of elastin were observed after tissue elastin specific staining.Results The gene expression of MMP-12 began to increase 1 week post irradiation,then decreased at 2 weeks,and it reached its peak value at 4 weeks,while its protein expression was elevated again 2 weeks post irradiation.MMP-12 was mainly expressed in macrophages and activated fibroblasts of the alveolar septum.With the elapse of time,the lung injury aggravated gradually,with thickening of alveolar wall and septum,breakdown of the structure of alveoli,collapss of a part of the alveolar space,extensive breakdown of elastin in the basement membrane of lung,appearing as irregular fibrils distributed in the lung.Conclusion 60Co ?-ray irradiation can up-regulate the expression of gene and protein of MMP-12 significantly,implying that it may play a very important role in early remodeling process in of radiation pulmonary injuries,and initiate the process of pulmonary remodeling by degrading elastin and destroying the normal structure of basement membrane.

Objective To observe the effects of over-expression of matrix metalloproteinase-12 (MMP-12) on the transformation of pulmonary fibroblasts in radiation damaged rats. Methods Thirty-two male Wistar rats (weighed 250-280g) were randomly assigned into control group and 1, 2 and 4 weeks after irradiation groups (8 each). The whole lungs of rats in irradiation groups were irradiated by 60 Co ?-ray at a dose of 20Gy, and the lung specimens were harvested 1, 2 and 4 weeks after radiation. The change of MMP-12 activity was detected by gelatin zymography, the degradation and collapse of elastic fibers were observed by tissue specific staining, the "cross talking" phenomenon between alveolar type Ⅱ cells and mesenchymal cells was observed by transmission electron microscopy, the content of TGF-?1 was determined by ELISA, and the expression of ?-smooth muscle actin (?-SMA) was examined by immunohistochemistry. Results MMP-12 activity began increasing 1 week after irradiation, and seemed to decrease 4 weeks after irradiation. Elastin, a part of the basement membrane of alveolar wall, began to degrade and collapse 1 week after radiation, and became worse 4 weeks after irradiation. The expressions of both TGF-?1 and ?-SMA were elevated gradually within 4 weeks after radiation. The "cross talking" phenomenon was found by electron microscopy between alveolar type Ⅱ cells and mesenchymal cells. Conclusions Increased activity of pulmonary MMP-12 has been found after radiation, which may promote the transformation of pulmonary fibroblasts by degrading elastin and ultimately initiate the pulmonary fibrosis.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members. RESULTS: The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%. CONCLUSION The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.
Epilepsy/genetics* ; Humans ; NAV1.1 Voltage-Gated Sodium Channel/genetics* ; Pedigree ; Phenotype ; Seizures, Febrile/genetics*

OBJECTIVETo analyze the status of acute upper respiratory infection and influenza-like illness (ILI) among community residents in Jinan in 2015, and to make a understand of the patient's medical treatment behavior and influenza vaccination coverage status in 2014.

METHODSBalloting method and convenient sampling method were used to launch a household survey. The residents who had been in Jinan for more than 3 months were selected, to investigate the residents' attack ratio of acute upper respiratory and influenza-like from Jan. 8 to Feb. 7, 2015. Totally, 1 300 persons from 410 families were involved in this survey which recovered 1 241 valid questionnaires with the efficiency of 95.5%. Based on the national age-urban demographic statistics in 2010, the attack rates of acute respiratory infections, influenza-like illness were estimated by the direct standardization method, and the influenza vaccination rates were also calculated in this study. χ(2)-test method was used to compare the different status of incidence and vaccination among residents with different features.

RESULTSThe attack rate of acute upper respiratory infection and influenza-like illness in Jinan from January 8, 2015 to February 7, 2015 were 30.2% (375 cases), and 6.1% (76 cases), respectively, with a standardized rate of 29.1% and 5.4%. 5.3% (66 cases) of the residents have vaccinated with the influenza vaccine inoculation, with an adjusted rate of 3.8%. The attack rate difference of acute upper respiratory tract infections was statistically significant between each age group (χ(2)=17.121, P= 0.002). The 0-4 age group had a highest attack rate (45.4%) of acute respiratory infection, while the 15-24 age group got the lowest (26.5%). 38.9% (146 cases) of patients went for a treatment in hospital. Among them, 37.7% (55 cases) of them selected the county level hospitals for treatment, 37.7% (55 cases) selected the community level hospitals, and 24.6% (36 cases) selected the individual clinic. Significant differences of influenza-like illness attack rate between each age group were also found in this study (χ(2)=76.79, P<0.001). 0-4 age group had the highest attack rate (22.7%). 81.6% (62 cases) of the ILI sought treatment in the hospital, of which 53.2% (33 cases) selected county level hospital or above, and 33.9% (21 cases) selected community hospital, and 12.9% (8 cases) selected the individual clinic.

CONCLUSIONThe attack rate of acute upper respiratory infections among the residents of Jinan was high, whereas that of influenza-like illness was relatively low. 0-4 age group had a higher risk of ILI than other age groups. Most of the cases were likely to take the treatment in large hospitals. In general, the coverage rate of influenza vaccination was relatively low.

Ambulatory Care Facilities ; China ; Hospitals ; Humans ; Influenza Vaccines ; administration & dosage ; Influenza, Human ; epidemiology ; Respiratory Tract Infections ; epidemiology ; Surveys and Questionnaires ; Vaccination ; statistics & numerical data

Objective To better understand the infection status of HIV in the patients seeking medical care in Peking Union Medical College Hospital.Methods The HIV detection data of the patients in the hospital from 2003-2014 were collected for a statistical analysis with software SPSS 19.0.Results A total of 715 421 patients were screened,and 1 012 (0.14％) patients were HIV positive,and HIV infection were confirmed in 776 (0.11％) patients by Western Blot testing.The detection rate of HIV infection increased from 0.05％ in 2003 to 0.17％ in 2014 (trend x2=66.83,P=0.000),and the increase during 2012-2014 was obvious.Of the 776 newly diagnosed HIV-infected individuals,631 (81.31％) were men and 145 (18.69％) were women.The percentage of the males infected with HIV increased from 50.00％ to 90.26％ (trend x2=58.41,P=0.000).The median age was 36 years (interquartile range:27-43),and the age group 18-50 years were mostly affected.In the 776 patients infected with HIV,634 (81.70％) were infected through sexual contacts,and the proportion of sexual transmissions increased with year (trend x2=126.38,P=0.000).The proportion of infected men who have sex with men (MSM) increased from 0％ in 2003 to 53.90％ in 2014 (trend X2=11.96,P=0.001),similar to the trend in western countries.The proportion of infected patients who were not married increased from 18.75％ to 42.21％ (trend x2=43.74,P=0.000).The top three source departments of HIV/AIDS cases were internal medicine (51.03％),emergency room (18.30％) and dermatology (13.53％).The proportion of the HIV/AIDS patients from department of gynecology and obstetrics declined from 18.75％ in 2003 to 2.60％ in 2014.No HIV/AIDS patients were detected in department of surgery,department of otorhinolaryngology,department of ophthalmology,department of stomatology and health examination center in 2003,but 14 cases (9.10％),11 cases (7.14％) and 4 cases (2.60％) were detected in these departments respectively in 2014.Conclusion The HIV detection rate increased with year in Peking Union Medical College Hospital,suggesting the necessity of strengthened HIV test in general hospitals.MSM are the population at high risk,to whom more attention should be paid.

Objective:To understand the infection rate of Coronavirus Disease 2019 (COVID-19) in close contacts in Shandong province and explore the risk factors of infection.Methods:All data from close contacts of 2019 novel coronavirus (2019-nCoV) infected persons in Shandong province were collected for descriptive epidemiological analysis, and risk factors were analyzed by logistic regression.Results:Up to March 6, 2020, a total of 15 702 close contacts had been reported in Shandong province, of whom 321 cases were infected with 2019-nCoV, with an infection rate of 2.04%. Among all the factors, the top five with the highest infection rate were close relatives (13.39%), frequent contact (9.58%), working/living/studying in the same room (7.54%), two or more contact cases (4.58%), and over 60 years old (3.10%). Single-factor analysis showed that exposure to two or more cases, over 60 years old, close relatives with cases, frequent contact and working/living/studying in the same room were the risk factors for infection in close contacts. Multivariate analysis showed that exposure to two or more cases ( OR=2.510, 95% CI: 1.843-3.417), 30~60 year old group ( OR=1.513, 95% CI: 1.141-2.007), frequent exposure group ( OR=20.025, 95% CI: 14.625-27.419), working/living/learning in the same room ( OR=2.406, 95% CI: 1.385-4.182) and medical institution exposure ( OR=2.366, 95% CI: 1.149-4.871) were risk factors of infection in close contacts. Conclusions:Tracking and managing close contacts was an important measure to control the COVID-19 epidemic situation, and reducing crowd concentration, keeping a proper social distance and taking effective protection were effective measures to control 2019-nCoV infection.

Objective:To evaluate the efficacy and safety of a novel domestic pulmonary thromoboectomy system Tendvia TM in the treatment for high-risk patients complicated with acute pulmonary embolization (APE). Methods:The study was designed as a prospective single-center clinical trial. Twenty-four high-risk patients with APE were recruited and underwent percutaneous mechanical thromoectomy (PMT) with the Tendvia TM pulmonary thromoboectomy system. The primary efficacy endpoint was the reduction of RV/LV ratio at the post-operative 48 h. The secondary efficacy endpoints included technical success rate, mean pulmonary arterial pressure (mPAP), arterial PaO 2 and the instant post-operative thrombus clearance rate. The evaluation of the safety included the intraoperative complications and related complications during the follow-up period associated with the PMT operation and the major adverse event (MAE) rate within the post-operative 48 h. The pre-and post-operative data were compared with paired sample t-test or Wilcoxon rank sum test to evaluate the efficacy and safety of Tendvia TM pulmonary thromoboectomy system. Results:The technical success rate of PMT with Tendvia TM pulmonary thromoboectomy system was 100% (24/24). The 48 h pre-operative RV/LV ratio was 1.19±0.25 and the post-operative RV/LV ratio was 0.82±0.16. The mean RV/LV ratio of the patients was decreased by 0.37±0.25 at post-operative 48 h with significant statistical difference ( t=7.03, P<0.001). The 48 h pre-operative mPAP was (31.09±6.09) mmHg and the post-operative mPAP was (25.91±4.36) mmHg. The mPAP of the patients was reduced by 5.18 mmHg at post-operative 48 h with significant statistical difference ( t=6.73, P<0.001). The pre-operative PaO 2 was (74.66±11.28) mmHg and the post-operative PaO 2 was (88.01±10.57) mmHg. The pressure of oxygen in artery was increased by 13.36 mmHg. The differences were statistically significant( t=-4.08, P<0.001). The rate of thrombus removal was 68.17%±22.66%. 87.5% (21 cases) of patients achieved a thrombus removal greater than grade Ⅱ. One patient underwent catheter directed thrombolysis (CDT) after PMT based on the evaluation of operator. The patient′s thrombus removal achieved grade Ⅲ after 48 h and the CDT was ceased. Hemoptysis occurred intra-operatively in one case underwent PMT and the symptom of the patient was alleviated with conservative medication. The MAE incidence within the post-operative 48 h was 4.17% (1/24). No device-related mortality or all-cause mortality occurred in the trial. Conclusions:The Tendvia TM pulmonary thromoboectomy system is a safe and effective device to remove the pulmonary arterial thrombus for the treatment of patients with APE. The Tendvia TM pulmonary thromoboectomy system can be a new choice in the treatment for the patients with APE.

Objective:To study the infection of human rhinovirus, respiratory syncytial virus and human adenovirus in Jinan from April 2018 to March 2019, and analyze epidemiological characteristics of human adenovirus.Methods:All of 1969 nasopharyngeal swabs were collected from hospitalized patients with acute respiratory tract infections in The Fourth People’s Hospital of Jinan, Qilu Children′s Hospital of Shandong University, Peoples Hospital of Zhangqiu District from April 2018 to March 2019, fluorescence quantitative PCR was used to detect the positive rate of human rhinovirus, respiratory syncytial virus and human adenovirus. Seven adenovirus positive samples were isolated and examined by sequencing, then we determined adenovirus type, constructed gene phylogenetic trees for analysis.Results:Of the 1969 samples, 242 were positive, the total positive rate was 12.30% (242/1969), the positive rate was 3.00% (59/1969) for rhinovirus, 6.30% (124/1969) for respiratory syncytial virus (RSV), and 3.86% (76/1969) for adenovirus. There was no significant difference in the detective rate of rhinovirus in different age groups (Fisher′s exact test value =8.376, P=0.720), the positive rates of RSV and adenovirus in different age groups was statistically significant ( χ2=19.28, 12.16; P=0.001, 0.016). There was a statistically significant difference in the positive rate of adenovirus between different sexes ( χ2=14.33, P<0.001), and there was no statistically significant difference in the positive rate of rhinovirus and RSV between males and females ( χ2=0.30, 2.90, P=0.862, 0.089). Comparing the positive rates of viral nucleic acid in different months, we found that the positive rate of rhinovirus, RSV and adenovirus separately reached the highest in October, December and November (8.61%, 26.50% and 8.84%). We constructed a gene phylogenetic tree after seven positive samples of adenoviruses were sequenced, by the molecular typing method we detected that seven adenovirus-positive samples were all HAdV-2 type. Conclusions:By comparing the epidemiological trends of human rhinovirus, RSV and human adenovirus in Jinan from April 2018 to March 2019 in different ages, genders, and months, providing reference basis for the early prevention and clinical treatment of acute respiratory tract infection.

Objective:To isolate and identify the virus from stool samples of children with hand, foot and mouth disease (HFMD) in Linyi City, Shandong Province in 2017, and analyze its genetic characteristics.Methods:Nucleic acid was detected in fecal specimens of children with hand, foot and mouth disease. Human rhabdomyosarcoma cells were used for virus isolation. The whole genome of the virus was sequenced, and the phylogenetic analysis and gene recombination analysis of the isolates were carried out by comparing with human enterovirus.Results:A coxsackievirus A group 2 type(CoV-A2), named SD17-430, was successfully isolated from fecal specimens of children with severe HFMD. Phylogenetic analysis further confirmed that the coxsackievirus genotype belonged to D2 genotype. The coding region of SD17-430 capsid protein had high homology with CoV-A2 international original strain, while the coding region of non-structural protein had high homology with CoV-A4 (MH086949) and CoV-A14 (KP036482).Conclusions:Compared with the original strain, CoV-A2 SD17-430 strain has a greater degree of genetic variation, and may have genetic recombination with multiple enteroviruses during its evolution. We should continue to strengthen the overall monitoring of HFMD pathogens in order to further understand the changes of pathogen spectrum and provide data reference for formulating more effective strategies for HFMD prevention and control.

Objective:To construct and rescue enhanced green fluorescent protein(EGFP)-labeled EGFP-EV-A71 recombinant virus.Methods:pMD19T-SDLY107 full-length plasmid was used as a template, and 2A protease recognition sequence was added to the 5′end of the structural protein VP4. EGFP gene was amplified using the pEGFP-N1 plasmid as a template and inserted into the above-mentioned recombinant plasmid. RD cells were transfected to rescue the recombinant virus EGFP-EV-A71 after enzymatic digestion and in vitro transcription. The cell culture infectious dose 50% endpoint (CCID 50) was determined. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the virus replication level at different time points, and the virus replication curve was drawn to compare the replication ability of the recombinant virus and the parent virus. Lactate dehydrogenase (LDH) and cell proliferation (CCK-8) experiments were used to determine the cell injury rate and survival rate of infected cells, respectively. Results:Recombinant EV-A71 infectious cDNA clones containing specific restriction sites and EGFP were successfully constructed. Typical cytopathic effect and green fluorescence was observed. The qRT-PCR replication curve showed that the recombinant virus had similar replication kinetics to the parent virus.Conclusions:EGFP-labeled enterovirus type 71 recombinant virus EGFP-EV-A71 was successfully rescued.