Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Objective:To analyze the clinical characteristics of patients with Vibrio vulnificus infection, share diagnosis and treatment experience, and establish a rapid diagnosis procedure for this disease. Methods:This study was a retrospective case series study. From January 2009 to November 2022, 11 patients with Vibrio vulnificus infection who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of Guangdong Provincial People's Hospital Affiliated to Southern Medical University. The gender, age, time of onset of illness, time of admission, time of diagnosis, route of infection, underlying diseases, affected limbs, clinical manifestations and signs on admission, white blood cell count, hemoglobin, platelet count, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, procalcitonin, albumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and blood sodium levels on admission, culture results and metagenomic next-generation sequencing (mNGS) results of pathogenic bacteria and the Vibrio vulnificus drug susceptibility test results during hospitalization, treatment methods, length of hospital stay, and outcomes of all patients were recorded. Comparative analysis was conducted on the admission time and diagnosis time of patients with and without a history of exposure to seawater/marine products, as well as the fatality ratio and amputation of limbs/digits ratio of patients with and without early adequate antibiotic treatment. For the survived patients with hand involvement, the hand function was assessed using Brunnstrom staging at the last follow-up. Based on patients' clinical characteristics and treatment conditions, a rapid diagnosis procedure for Vibrio vulnificus infection was established. Results:There were 7 males and 4 females among the patients, aged (56±17) years. Most of the patients developed symptoms in summer and autumn. The admission time was 3.00 (1.00, 4.00) d after the onset of illness, and the diagnosis time was 4.00 (2.00, 8.00) d after the onset of illness. There were 7 and 4 patients with and without a history of contact with seawater/marine products, respectively, and the admission time of these two types of patients was similar ( P>0.05). The diagnosis time of patients with a history of contact with seawater/marine products was 2.00 (2.00, 5.00) d after the onset of illness, which was significantly shorter than 9.00 (4.25, 13.00) d after the onset of illness for patients without a history of contact with seawater/marine products ( Z=-2.01, P<0.05). Totally 10 patients had underlying diseases. The affected limbs were right-hand in 8 cases, left-hand in 1 case, and lower limb in 2 cases. On admission, a total of 9 patients had fever; 11 patients had pain at the infected site, and redness and swelling of the affected limb, and 9 patients each had ecchymosis/necrosis and blisters/blood blisters; 6 patients suffered from shock, and 2 patients developed multiple organ dysfunction syndrome. On admission, there were 8 patients with abnormal white blood cell count, hemoglobin, and albumin levels, 10 patients with abnormal CRP, procalcitonin, and NT-proBNP levels, 5 patients with abnormal creatinine and blood sodium levels, and fewer patients with abnormal platelet count, ALT, and AST levels. During hospitalization, 4 of the 11 wound tissue/exudation samples had positive pathogenic bacterial culture results, and the result reporting time was 5.00 (5.00, 5.00) d; 4 of the 9 blood specimens had positive pathogenic bacterial culture results, and the result reporting time was 3.50 (1.25, 5.00) d; the mNGS results of 7 wound tissue/exudation or blood samples were all positive, and the result reporting time was 1.00 (1.00, 2.00) d. The three strains of Vibrio vulnificus detected were sensitive to 10 commonly used clinical antibiotics, including ciprofloxacin, levofloxacin, and amikacin, etc. A total of 10 patients received surgical treatment, 4 of whom had amputation of limbs/digits; all patients received anti-infection treatment. The length of hospital stay of 11 patients was (26±11) d, of whom 9 patients were cured and 2 patients died. Compared with that of the 6 patients who did not receive early adequate antibiotic treatment, the 5 patients who received early adequate antibiotic treatment had no significant changes in the fatality ratio or amputation of limbs/digits ratio ( P>0.05). In 3 months to 2 years after surgery, the hand function of 8 patients was assessed, with results showing 4 cases of disabled hands, 2 cases of incompletely disabled hands, and 2 cases of recovered hands. When a patient had clinical symptoms of limb redness and swelling and a history of contact with seawater/marine products or a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection. Conclusions:Vibrio vulnificus infection occurs most frequently in summer and autumn, with clinical manifestations and laboratory test results showing obvious infection characteristics, and may be accompanied by damage to multiple organ functions. Both the fatality and disability ratios are high and have a great impact on the function of the affected limbs. Early diagnosis is difficult and treatment is easily delayed, but mNGS could facilitate rapid detection. For patients with red and swollen limbs accompanied by a history of contact with seawater/marine products or with a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection.

Humans ; Asthma/drug therapy* ; Biological Therapy

OBJECTIVES: Type 2 diabetes (T2DM) is a common comorbidity in patients with degenerative aortic stenosis (AS).As a key item of the American Society of Thoracic Surgeons (STS) score, it has a vital impact on the clinical prognosis of traditional thoracic surgery. T2DM has an adverse effect on the morbidity and mortality of cardiovascular diseases. At the same time, studies have shown that T2DM are associated with myocardial hypertrophy and remodeling, decreased left ventricular function, and worsening heart failure symptoms in the AS patients. Transcatheter aortic valve replacement (TAVR) as an interventional method to replace the aortic valve has better safety for middle and high risk patients in surgery, but the impact of T2DM on the clinical outcome of TAVR in AS patients is not clear.By analyzing the clinical and image characteristics of patients with AS and T2DM who received TAVR treatment, so as to explore the effect of T2DM on the perioperative complications and prognosis of TAVR. METHODS: A total of 100 consecutive patients with severe AS, who underwent TAVR treatment and were followed up for more than 1 month, were selectedin the Second Xiangya Hospital of Central South University from January 2016 to December 2020.Among them, 5 patients who were treated with TAVR due to simple severe aortic regurgitation were not included, therefore a total of 95 patients with severe aortic stenosis were enrolled in this study.The age of the patients was (72.7±4.8) years old, and there were 58 males (61.1%), and the patients with moderate or above aortic regurgitation had 30 cases (31.6%). The patients were divided into a diabetic group and a non-diabetic group according to whether they were combined with T2DM.There was no statistical difference in age, gender, body mass index (BMI), STS score, and New York Heart Association (NYHA) cardiac function classification between the 2 groups (all P>0.05). The primary end point was defined as a composite event consisting of all-cause death and stroke one month after surgery, and the secondary end point was defined as TAVR-related complications immediately after surgery and one month after surgery.The preoperative clinical data, cardiac ultrasound data, CT data, postoperative medication and the incidence of each endpoint event were compared between the 2 groups.The predictive model of adverse events was constructed by single factor and multivariate logistic regression. RESULTS: Compared with the non-diabetic group, the diabetic group had high blood pressure and chronic renal insufficiency.There was no significant difference in preoperative ultrasound echocardiography between the 2 groups. Preoperative CT evaluation found that the anatomical structure of the aortic root in the diabetic group was smaller than that in the non-diabetic group, and there was no significant difference in the incidence of bicuspid aortic valve between the 2 groups (all P<0.05). In terms of postoperative medication, the use of statins in the diabetes group was significantly higher than that in the non-diabetic group. In the diabetes group, 6 patients (37.5%) received insulin therapy, and 9 patients (56.3%) received oral medication alone.Univariate logistic regression analysis showed that the all-cause death and stroke compound events was increased in the diabetes group in 30 days after TAVR (OR=6.86; 95% CI: 2.14 to 21.79; P<0.01). Heart disease (OR=2.80; 95% CI: 0.99 to 7.88; P<0.05) and chronic renal insufficiency (OR=3.75; 95% CI: 1.24 to 11.34; P<0.05) were also risk factors for all-cause death and stroke compound events.In a multivariate analysis, after adjusting for age, gender, BMI, comorbidities, N-terminal pro-B type natriuretic peptide (NT-proBNP), total calcification score, ejection fraction, and degree of aortic regurgitation, T2DM was still a risk factor for all-cause death and stroke compound events in 30 days after TAVR (OR=12.68; 95% CI: 1.76 to 91.41; P<0.05). CONCLUSIONS T2DM is a risk factor for short-term poor prognosis in patients with symptomatic severe AS after TAVR treatment. T2DM should play an important role in the future construction of the TAVR surgical risk assessment system, but the conclusions still need to be further verified by long-term follow-up of large-scale clinical studies.
Aged ; Aortic Valve/surgery* ; Aortic Valve Insufficiency/surgery* ; Aortic Valve Stenosis/surgery* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Renal Insufficiency, Chronic/complications* ; Risk Factors ; Severity of Illness Index ; Stroke ; Transcatheter Aortic Valve Replacement/methods* ; Treatment Outcome ; United States

A total of 159 patients with Streptococcus milleri (S. milleri) infection were diagnosed in our hospital between January 2014 and January 2019. The demographic data, underlying diseases, infection sites, laboratory tests, and prognosis of patients were retrospectively analyzed; the clinical and microbiological data were compared among different age groups. Of the 159 patients there were 103 were males and 56 females; there were 19 patients aged<18 years [(8.1±5.3) years], 113 patients aged ≥18 and < 65 years [(45.5±13.1) years] and 27 patients aged ≥65 years[(74.7±8.6) years]. The incidence peaked in the 34-55 year age group (50 cases, 31.4%). Streptococcus anginosus was identified in 97 cases (61.0%), Streptococcus constellatus in 55 patients (34.6%) and Streptococcus intermedius in 7 cases (4.4%). The abdomen (44 cases, 27.7%) and the chest (19 cases, 11.9%) were the main involving sites. For patients younger than 18 years and those aged ≥18 and<65 years, suppurative appendicitis was the most common condition[12 cases(12/19) and 21 cases(18.6%), respectively]; while in patients aged ≥65 years, chest infection ranked the first (9 cases, 33.3%). All 159 patients were treated with anti-infection therapy alone or anti-infection and invasive procedures with a favorable prognosis, 2 patients died with a overall fatality rate of 1.3%.

OBJECTIVES: To understand medical students' mental health, professional pride, and intention to work in the front-line during coronavirus disease 2019 (COVID-19) pandemic, and provide a reference for psychological intervention. METHODS: We used the depression-anxiety-stress scale and self-designed questionnaire on professional pride, intention to work in the front-line and the extent of family support. Medical students from 4 medical schools in Fujian and Hunan were investigated. Their mental health status, professional pride and first-line work willingness with different characteristics were compared, and the influential factors for professional pride and first-line work willingness were analyzed. RESULTS: A total of 266 valid questionnaires were collected. During the pandemic, there were significant differences in the proportion of depressed students among different college and universities, majors and stages (<0.05), and the professional pride was significantly different (<0.001). Medical students with different mental health status showed significant differences in professional pride (<0.01). Marriage, pressure and extent of family support were the influential factors for their professional pride (<0.05). The latter two were also influential factors for their intention to work in the front-line (<0.05). CONCLUSIONS During the pandemic, students from college and nursing have relatively better mental health and higher professional pride. The professional pride is low in medical students who married, with abnormal stress or low family support. The intention to work in front-line is decreased in students with abnormal stress or low family support.
Betacoronavirus ; China ; Coronavirus Infections ; psychology ; Family ; Humans ; Intention ; Mental Health ; Pandemics ; Pneumonia, Viral ; psychology ; Professionalism ; Social Support ; Stress, Psychological ; Students, Medical ; psychology ; Surveys and Questionnaires

Unroofed coronary sinus syndrome (UCSS), also named coronary sinus septal defect, is a rare type of atrial septal defect with the incidence less than 1% of the total number of atrial septal defects. It is caused by incomplete formation of left atrial venous folds during embryonic development. Here we reported a patient with UCSS, who was treated in the Second Xiangya Hospital of Central South University. The patient was 50 years old and the main clinical manifestations were fatigue and shortness of breath after repeated exercise. Color Doppler echocardiography showed coronary sinus dilatation (17 mm×14 mm), indicating the possibility of permanent left superior vena cava. Pulmonary angiography showed that the left ventricle and coronary sinus were developed at the same time while the atrial septum was intact after the development of the left atrium, followed by the right atrium and right ventricle, indicating a partial anomalous pulmonary venous drainage (intracardiac type). Finally, the cardiac computed tomograhic angiography showed that 4 pulmonary veins and permanent left superior vena cava (PLSVC) went into the left atrium and the coronary sinus, respectively, while the coronary sinus septum was absent and the PLSVC was connected with the left atrium. The patient was later treated with the correction of non-parietal sinus syndrome in the Cardiovascular Surgery Department of our hospital.
Coronary Sinus ; Heart Atria ; Heart Septal Defects, Atrial ; Humans ; Middle Aged ; Vena Cava, Superior

Objective To evaluate the effects of diagnostic and treatment manipulation of the urinary diseases on serum prostate specific antigen(PSA) levels .Methods 80 male patients were recruited from urology surgery department of Shenzhen Tranditional Chinese Medicine (TCM ) Hospital ,Which included 13 cases with digital rectal examination (DRE) ,10 cases with catheterization , 12 cases with rigid cystoscopy ,17 cases with prostate biopsy ,28 cases with transurethral resection of the prostate (TURP) .Blood samples of 80 patients were collected before diagnostic and treatment manipulation of the urinary diseases and 24 h ,3 d ,7 d ,14 d af‐ter that ,respectively .Then ,serum total prostate antigen(TPSA) and free prostate antigen (FPSA) was measured .Results There was no effects of DRE on serum TPSA and FPSA levels(P>0 .05) .On the contrary ,serum TPSA and FPSA levels increased sig‐nificantly in patients with catheterization and cystoscopy(P<0 .05) ,and the duration was longer(7-14 d) .Serum TPSA and FPSA levels increased significantly(P<0 .05)in patients with TURP and biopsy at the 24th hour after manipulation and it began to de‐crease on the third day .Also ,the serum TPSA and FPSA levels decreased to baseline after 14 days .Conclusion There′re no effects of DRE on serum TPSA and FPSA levels .However ,serum TPSA and FPSA levels increase differently in patients with catheteriza‐tion ,cystoscopy ,biopsy and TURP ,but the durations were different ,too .

Objective To observe the clinical efficacy ofErxian Decoction combined with elcatonin for the treatment of postmenopausal osteoporosis.Methods Eighty cases of female patients with postmenopausal osteoporosis were randomly divided into treatment group and control group, 40 cases in each group. The control group received intramuscular injections elcatonin treatment, and the treatment group received oralErxian Decoction on the basis of the treatment of the control group, for 12 weeks. The main clinical symptom score, VAS score and bone mineral density (BMD) of L2-L4 and in the tibia of the two groups were observed before and after treatment to assess the therapeutic effect.Results After treatment, VAS scores of the two groups were significantly lower (P<0.05). The total effective rate of the treatment group was 92.5% (37/40); the control group was 75.0 (30/40), with statistical significance (P<0.05). The treatment group was significantly better than the control group in main symptom scores, especially in improving body symptoms (P<0.05). BMD of the treatment group was significantly higher than the control group.ConclusionErxian Decoction combined with elcatonin therapy for postmenopausal women with osteoporosis can significantly improve clinical symptoms and increase BMD.

Objective To investigate the impact of intermittent porta hepatis occlusion on postoperative intra-hepatic recurrence of hepatocellular carcinoma.Methods We retrospectively reviewed the records of 335 patients who underwent partial hepatectomy.The patients were classified into 2 groups:(1) the study group (n=97):porta hepatis was occluded with intermittent Pringle maneuver with 2-3 cycles of clamp/unclamp time of 15 min/5 min,repeated 2-3cycles; (2) the control group (n=238):including using Pringle maneuver,preconditioning occlusion of porta hepatis and selective occlusion of portal blood inflow.Patients were followed-up in the Outpatient Department once every 2-3 weeks in the 1st year,and once every 3-6 weeks in the 2nd year with US/CT/MRI and serum AFP test.The mean duration of follow-up was 26.5 months.Results The perioperative mortality was 1.8％ (6/335).Tumour recurrence in the study group was 31.6％ and 48.4％ in the 1st and 2nd year,respectively.The recurrence rates were significantly higher,than the 21.4％ and 38.0％ in the control group (P＜0.05).To exclude the miscellaneous factors which were involved in intra-hepatic recurrence of HCC,we set up 3 criteria to include patients for subgroup analysis:tumor ≥5 cm; serum AFP decreased to normal level within 4 weeks; negative intra-operative US scan.The number of patients included were 79 and 155 in the study and the control groups,respectively.There were significant differences in recurrence rate between the study and the control groups in the 1st and 2nd year (29.1％ vs 18.7％,46.8％ vs 35.5％,P＜0.05).There were no significant differences in overall survival rate between the two groups.Conclusions Intermittent porta hepatis occlusion is a risk factor of postoperative intra hepatic recurrence of hepatocellular carcinoma.