eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective:To investigate the pathogen spectrum and the epidemiological characteristics of hospitalized severe acute respiratory tract infection (SARI) cases in a sentinel hospital in Tongzhou District of Beijing from 2019 to 2022, and provide reference for scientific prevention and control of SARI.Methods:This study enrolled SARI patients in the Beijing Luhe Hospital from January 2019 to December 2022. Nasopharyngeal swabs or respiratory secretions of the patients were collected and analyzed by quantitative real-time PCR to detect the pathogens and their types. The epidemiological and clinical characteristics of the cases were analyzed.Results:In this study, 1 124 SARI cases were enrolled, of which 379 were positive for respiratory pathogens with a detection rate of 33.72%. Most of the SARI cases were positive for bacteria pathogens, and the detection rates of Mycoplasma pneumoniae, Streptococcus pneumoniae, and Stenotrophomonas maltophilia were high. Influenza A virus, parainfluenza virus, and respiratory syncytial virus were the main viral pathogens detected in the cases. There were significant differences in the number of cases and the detection rate of respiratory pathogens among different age groups (χ 2=555, P=0.000 1). The predominant pathogens in different years were different. Mycoplasma pneumoniae [27.27% (51/187)] and influenza A virus [17.65% (33/187), ] were the predominant pathogens in 2019; parainfluenza virus [16.67% (10/60)], Mycoplasma pneumoniae [11.67% (7/60)], and Haemophilus influenzae [11.67% (7/60)] were the predominant pathogens in 2020; Stenotrophomonas maltophilia [24.39% (20/82)] and respiratory syncytial virus [19.51% (16/82)] were the predominant pathogens in 2021; Stenotrophomonas maltophilia [20% (10/50)] and parainfluenza virus [12% (6/50)] were the predominant pathogens in 2022. Conclusions:Most of the SARI cases in Tongzhou district of Beijing from 2019 to 2022 are caused by bacteria. More attention should be paid to the prevalence of Stenotrophomonas maltophilia and Mycoplasma pneumoniae, as well as the prevalence of respiratory syncytial virus, parainfluenza virus, and influenza A virus. The predominant pathogens change every year from 2019 to 2022. Therefore, the prevention and control strategies should be made accordingly. This study provides basis data for the national respiratory multipathogen surveillance program.

Objective:To investigate the role of integrin-linked kinase (ILK)-small interfering RNA (siRNA)-adeno-associated virus (AAV) in scar formation after glaucoma filtering surgery in rat eyes.Methods:Forty-eight Sprague Dawley rats of SPF grade, aged 8 to 9 weeks old, were selected and divided into blank control group, ILK-siRNA-AAV group, NC-siRNA-AAV group and mitomycin C (MMC) group by random number table method, with 12 rats in each group.Left eyes of the rats were taken as experimental eyes, and no intervention was administered to fellow eyes.The bulbar conjunctival filtering bleb after glaucoma filtration surgery in rats was established by anterior chamber drainage tube implantation.One day after operation, phosphate buffer solution, ILK-siRNA-AAV, and NC-siRNA-AAV were injected into the filtering bleb of blank control group, ILK-siRNA-AAV group and NC-siRNA-AAV group, 5 μl each group, respectively.Cotton tablets containing 0.4 mg/ml MMC were placed under conjunctival flap for 5 minutes during operation in MMC group.Intraocular pressure (IOP) was measured with a handheld tonometer before surgery and at 1, 2, 3, 7, 14, 21, 28 days after surgery.Formation of filtering blebs in rats was observed with a surgical microscope at 1, 2, 3, 7, 14, 21, 28 days after operation, and the bleb survival time was calculated by Kaplan-Meier survival analysis.The mRNA and protein expression levels of ILK in conjunctival and subconjunctival tissues at the surgical sites were detected by reverse transcription PCR and Western blot, respectively, on the 28th day after operation.Silencing of ILK gene was identified.Effect of ILK gene silencing on the morphology of drainage pathway was observed by hematoxylin-eosin staining.Effect of ILK gene silencing on collagen fiber deposition in the bulbar conjunctiva at filtration area was examined by Masson staining, and the percentage of positive area of collagen fiber staining in the total tissue visual field was calculated.The use and care of the animals complied with the ARVO Statement.This research protocol was approved by an Ethics Committee of Xi'an Jiaotong University (No.2013-772). Results:There were statistically significant differences in IOP at different time points between before and after surgery among four groups ( Fgroup=76.84, P<0.001; Ftime=114.49, P<0.001). The IOP of ILK-siRNA-AAV group on the 1st, 7th, 14th and 28th day after operation and the IOP of MMC group on the 2nd, 3rd, 7th, 14th and 28th day after operation were lower than those of blank control group, and the differences were statistically significant (all at P<0.05). The IOP of ILK-siRNA-AAV group was lower on 7th, 14th, 21st and 28th day after operation than those of NC-siRNA-AAV group, with statistically significant differences (all at P<0.05). The bleb survival time of blank control group, NC-siRNA-AAV group, ILK-siRNA-AAV group and MMC group was (3.50±1.51), (5.00±3.41), (31.50±3.15) and (31.33±2.46) days, respectively, with a significant difference among them ( F=395.83, P<0.05). The bleb survival time of ILK-siRNA-AAV group and MMC group was higher than that of blank control group and NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in the relative expression levels of ILK mRNA and protein among four groups ( F=222.32, 752.69; both at P<0.05), and the relative expression levels of ILK mRNA and protein were significantly lower in ILK-siRNA-AAV group than blank control group and NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). Proliferative fibrous connective tissue and a large number of cells at surgical sites were found in blank control group and NC-siRNA-AAV group, and the fibroblasts were of a high density and grew in clumps.In ILK-siRNA-AAV group, the bulbar conjunctiva was thin, and the arrangement of fibrous connective tissue was loose, and a few proliferative fibroblasts were found.In MMC group, the conjunctival fibrous layer was loose and thin, forming cavities, and scarce cells were found.There was statistically significant difference in the percentage of collagen fiber positive staining area among four groups ( F=741.66, P<0.05). The positive staining percentage of ILK-siRNA-AAV group and MMC group was significantly lower than that of blank control group, among which there was lower positive staining percentage in ILK-siRNA-AAV group than NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). Conclusions:Silencing of ILK can inhibit the scar formation after glaucoma filtering surgery and maintain low IOP in rats.

Objective:To analyze the serum lipid levels, and its influencing factors, of male residents around an uranium mine in order to provide a scientific basis for health risk assessment for such residents.Methods:With such a mine as the center, the surveyed subjects were divided into four groups as within 5, 10, 15 and 20 km of this mine, respectively. These male residents living around the mine were randomly selected as subjects. A health questionnaire survey was conducted among the subjects. The indicator such as height, weight and blood pressure were measured by means of the standard method. Peripheral venous blood was extracted from the subjects, and their venous blood glucose and serum lipid were detected. The levels of serum lipid and detectable rates of abnormal serum lipid were analyzed by using univariate analysis, and multivariate logistic regression analysis was used to analyze the influencing factors of dyslipidemia.Results:A total of 867 males at age 40 to 69 was included in the vicinity of the mine. The mean levels ( ± s) of TC, TG, LDL-C, and HDL-C were (5.46±1.11), (1.92±1.64), (3.19±1.02), and (1.39±0.43) mmol/L, respectively. 384 subjects with dyslipidemia were totally detected in the residents, and the detection rate was 44.29% (384/867). Of the residents with dyslipidemia, the majority was abnormal in two lipid related indexes (45.57%, 175/384). Univariate analysis result showed that there was statistically significant difference in TG level in different distance groups ( F=3.34, P<0.05). There were statistically significant differences in the abnormal detection rates of TG and HDL-C in subjects in different distance groups ( χ2=9.52, 10.18, P<0.05). The detection rates of dyslipidemia were significantly different in the groups of BMI, blood pressure and blood glucose ( χ2=45.91, 32.31, 11.42, P<0.05). Multivariate logistic regression analysis showed that excluding marital status and degree of education, the BMI, blood pressure and blood glucose all had an impact on dyslipidemia. The residents with overweight ( OR=2.08, 95% CI: 1.52-2.86) and obeseness ( OR=2.88, 95% CI: 1.58-5.24) had a higher risk for dyslipidemia than those with normal weight. The risks for dyslipidemia in the residents with hypertension ( OR=1.94, 95% CI: 1.45-2.60) and hyperglycemia ( OR= 2.17, 95% CI: 1.27-3.69) were higher than those with normal blood pressure and blood glucose, respectively. Conclusions:The detection rate of dyslipidemia is higher in male residents around the mine. The BMI, alcohol consumption, blood pressure, blood glucose and distance from the mine are influencing dyslipidemia and other relevant indexes. Overweight is an independent risk factor for dyslipidemia and its components. The distances from uranium mine has no significant effect on the dyslipidemia of male residents.

Objective:To investigate the clinical characteristics and surgical treatment experience of carotid body tumor (CBT).Methods:The clinical data of 12 patients with CBT admitted to the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University from March 2013 to August 2020 were analyzed retrospectively. Among them, there were 6 males and 6 females, aged 31-83 years, with a median age of 57 years. Among the 12 patients, 2 patients were not treated surgically. The body mass index (BMI), tumor side, maximum diameter of tumor, and tumor classification, operation time, intraoperative bleeding volume, postoperative drainage volume and time, postoperative hospital stay and postoperative complications of patients undergoing surgery were recorded.Results:BMI of the 12 patients was 17.19-29.07 kg/m 2, with an average of (24.05±3.95) kg/m 2. Among the 12 patients, there were 4 tumors on the left side, 6 tumors on the right side and 2 patients had bilateral tumors. The maximum diameter of the tumor was 1.7-8.7 cm, with an average of (4.05 ± 1.89) cm. Among the 2 patients with bilateral tumors, 1 patient underwent staged resection within 9 months and 1 patient only removed the larger tumor. A total of 10 patients underwent surgical resection. All excised tumors were confirmed histopathologically to be paraganglioma. The average operation time and the amount of bleeding was(164.73 ± 74.39)min and 341.82 mL respectively. The drainage time was 1-3 d, with an average of (1.73 ± 0.65) d. The cumulative drainage volume was 22-237 mL, with an average of (77.18 ± 57.47) mL. Classification of 11 surgically resected tumors: 3 patients (3/11, 27.3%) were Shamblin Ⅰ, 7 patients (7/11, 63.6%) were Shamblin Ⅱ and 1 patient (1/11, 9.1%) were Shamblin Ⅲ. There were 1 patient of hematoma and 1 patient of acute cerebral infarction after operation. One patient with decrease in muscle strength of right limb, other surgical patients complained no complications such as stroke and cranial nerve injury when discharged. Patients undergoing surgery were hospitalized for 8-20 days, with an average of (13.36 ± 3.61) d. Conclusions:CBT is a rare paraganglioma in clinic. Surgical resection is an effective method to treat CBT. Careful operation should be carried out to avoid serious complications such as wound hematoma, cranial nerve injury and ischemic stroke.

Objective:To investigate the clinical characteristics, treatment, and prognostic factors of pancreatic neuroendocrine tumors (pNETs) patients treated with Sunitinib.Methods:The clinical data of pNETs patients from Pfizer Drug Assistance Program of Cancer Foundation of China from April 2013 to November 2017 were retrospectively analyzed. Follow-up and statistical analysis were performed.Results:A total of 235 patients were enrolled, the patients′ overall survival time was between 4 and 252 months, the 3-years and 5-years survival rates were 73.8% and 60.8%, respectively. Univariate analysis showed that factors such as age, Ki-67 index and surgery were associated with the 3-years survival rates of pNETs patients ( P<0.05). Multivariate analysis demonstrated that the age, Ki-67 index and surgery were independent prognostic factors for pNETs patients ( P<0.05). For patients with liver metastases, univariate analysis revealed that surgery was associated with prognosis ( P<0.05). The 5-years survival rate of 124 patients with extending usage of Sunitinib was 53.3%. Conclusion:PNETs are rare tumors with atypical clinical symptoms and the patients often have metastasis at the initiate diagnosis. The age, Ki-67 index and surgery are associated with the prognosis of pNETs patients.

Objective: To investigate oral health related quality of life and associated factors of adolescents between 12 and 15 years old, and to provide countermeasures and suggestions for oral health promotion of adolescents. Methods: This cross-sectional study recruited 3 840 adolescents aged 12-15 through multi-stage stratified cluster sampling method. The oral clinical examination and oral health questionnaire were conducted. Descriptive analysis, non-parametric testing and logistic regression analysis were used to analyze the oral health-related quality of life and associated factors. Results: Oral problems showed moderate to severe impact on quality of life,especially on eating (27.1%). Ordinal Logistic regression analysis showed that low sugar intake frequency, few teeth with gingival bleeding, no history of dental pain in the past 12 months,no history of tooth injuries, and administrative region of residence (Nanhai, Shunde) were associated with higher oral health-related quality of life,(OR=0.6-0.8，P<0.05). Conclusion The oral health-related quality of life of adolescents in Foshan was slightly better than the average national level. It is recommended to accurately formulate and ensure the full implementation of oral public health measures based on the comprehensive analysis of the local area, and combine various efforts to strengthen education on reducing excessive intake of sugar, prevent gingival bleeding, relieve and treat toothache in time, pay attention to adolescents with histories of dental trauma, and update the concepts of receiving oral health examination for the adolescents themselves, parents and teachers, and help adolescents develop the habit of regular oral examinations.

Objective:To investigate the clinical characteristics, treatment, and prognostic factors of pancreatic neuroendocrine tumors (pNETs) patients treated with Sunitinib.Methods:The clinical data of pNETs patients from Pfizer Drug Assistance Program of Cancer Foundation of China from April 2013 to November 2017 were retrospectively analyzed. Follow-up and statistical analysis were performed.Results:A total of 235 patients were enrolled, the patients′ overall survival time was between 4 and 252 months, the 3-years and 5-years survival rates were 73.8% and 60.8%, respectively. Univariate analysis showed that factors such as age, Ki-67 index and surgery were associated with the 3-years survival rates of pNETs patients ( P<0.05). Multivariate analysis demonstrated that the age, Ki-67 index and surgery were independent prognostic factors for pNETs patients ( P<0.05). For patients with liver metastases, univariate analysis revealed that surgery was associated with prognosis ( P<0.05). The 5-years survival rate of 124 patients with extending usage of Sunitinib was 53.3%. Conclusion:PNETs are rare tumors with atypical clinical symptoms and the patients often have metastasis at the initiate diagnosis. The age, Ki-67 index and surgery are associated with the prognosis of pNETs patients.

Objective:To explore the method and effect of endovascular treatment to innominate artery stenosis or occlusion.Methods:The data of 11 patients with stenosis or occlusion of innominate artery from January 2014 to November 2019 at Xuanwu Hospital of Capital Medical University were collected. All patients received endovascular treatment. We summarized the changes of clinical symptoms, surgical methods, perioperative complications, stent patency, and analyzed the changes in systolic blood pressure and peak blood flow velocity on the involving side.Results:All 11 patients underwent endovascular treatment. The surgical technique success rate was 100%. All patients were followed up. The follow-up time was 4-69 months, with an average of (30.1±23.4)months. 2 patients used cerebral umbrella during the operation. 1 patient was performed ipsilateral carotid endarterectomy, 1 patient underwent contralateral carotid stent implantation, 1 patient was diagnosed as severe stenosis of the innominate artery and left common carotid artery, and an innominate artery stent implantation was performed at one stage, left common carotid artery stent implantation was performed after half a year. We done operation from the femoral artery puncture approach (6 patients), brachial artery puncture approach (2 patients), axillary artery and femoral artery puncture approach (1 patients), and right common carotid artery and the femoral artery puncture approach (2 patients). 3 patients had in-stent restenosis at 6, 7and 12 months after stenting, respectively. 1 patient underwent balloon dilatation, and 2 patients underwent re-stent implantation. We have not do further intervention to 1 case of in-stent occlusion occurred 14 months after the stenting, for the clinical symptoms did not improve significantly. The clinical re-intervention rate in this group was 3/11, and the primary patency rate was 7/11. The secondary patency rate was 10/11. The symptoms of 10 patients were relieved and the weakness of right upper extremity was not significantly changed in 1 patient. No puncture point complications occurred in all patients, and no cerebral infarction occurred during the perioperative period. There were statistically significant differences in systolic blood pressure, blood pressure difference and peak blood flow velocity before and after the operation ( P<0.05). Conclusions:Endovascular treatment of innominate arterial stenosis or occlusion was safe and effective, and the appropriate surgical approach and plan should be selected according to the lesion characteristics and the whole body conditions.

Objective:To analyze the molecular epidemiology and virulence characteristics of polymyxin-resistant Klebsiella pneumoniae ( K. pneumoniae). Methods:From 2011 to 2016, 1 376 strains of K. pneumoniae were isolated from various clinical specimens of hospitalized patients in First Affiliated Hospital of Wenzhou Medical University. Agar dilution method was used to screen out the polymyxin-resistant strains.Polymerase chain reaction (PCR) was used to detect the genes related to polymyxin resistance, and real-time fluorescence quantitative PCR was used to detect the relative mRNA expression level of drug resistant genes. Pulsed-field gel electrophoresis, multilocus sequence typing and Galleria mellonella larvae infection model were performed to analyze the molecular epidemiological and virulent characteristics. Results:A total of 14 strains (1.02%) of polymyxin-resistant K. pneumoniae were detected among 1 376 K. pneumoniae isolates. Subsequent sequencing identified mutations leading to amino-acid changes (K2E, F28C) in MgrB of 10 isolates and D150G in PhoQ of nine isolates, and genes such as mcr and crrB were not detected in all drug-resistant strains. Compared with standard strains, the relative expression levels of pmrH and pmrD mRNA of these drug resistant strains were increased. Analysis of the molecular epidemiology indicated that the 14 drug-resistant strains were divided into nine clones. Galleria mellonella larvae infection model revealed polymyxin-resistant K. pneumoniae isolates had higher virulence. Conclusions:Polymyxin-resistant K. pneumoniae has mutations in mgrB and phoQ genes, and mgrB mutation may play a key role in the change of virulence profiles. The homology among the polymyxin-resistant K. pneumoniae stains in this study is low.