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Background and Purpose: Paravertebral arteriovenous shunts (PVAVSs) are rare. Whether the intradural venous system is involved in drainage may lead to differences in clinical characteristics through specific pathophysiological mechanisms. This study aims to comprehensively evaluate the natural history and clinical outcomes of PVAVSs with or without intradural drainage. Methods: Sixty-four consecutive patients with PVAVSs from 2 institutes were retrospectively reviewed. Lesions were classified as type A (n=28) if the intradural veins were involved in drainage; otherwise, they were classified as type B (n=36). The clinical course from initial presentation to the last follow-up was analyzed. Results: The patients with type A shunts were older at presentation (52.5 versus 35.5 years, P P =0.00006). After presentation, the deterioration rates related to gait and sphincter dysfunction were significantly higher in patients with type A than type B shunts (gait dysfunction: 71.8%/y versus 17.0%/y, P =0.0006; sphincter dysfunction: 63.7%/y versus 11.3%/y, P =0.0002). According to the angiogram at the end of the latest treatment, 79% of type A and 75% of type B PVAVSs were completely obliterated. If the lesions were partially obliterated, a significantly higher clinical deterioration rate was observed in patients with type A shunts than those with type B shunts (69.9%/y versus 3.2%/y, P =0.0253). Conclusions: Type A PVAVSs feature rapid progressive neurological deficits; therefore, early clinical intervention is necessary. For complex lesions that cannot be completely obliterated, surgical disconnection of all refluxed radicular veins is suggested.

Background New ischemic cerebral lesions (NICL) are commonly occur after carotid artery stenting (CAS) with an incidence rate ranging from 18-58% and are detected by diffusion-weighted imaging-magnetic resonance imaging (DWI-MRI). Numerous studies have reported that NICL could increase the risk of future cerebrovascular events and cognitive impairment. This systematic review and meta-analysis aimed to identify risk factors for NICL after CAS. Methods Relevant literature reporting risk factors for NICL after CAS were searched. Randomized controlled trials, case-control studies, or cohort studies were included in accordance with the pre-specified eligibility criteria. The risk of bias was assessed using the Cochrane Collaboration criteria and the quality of evidence was assessed with the corresponding scale. Data were analyzed using the RevMan V. 5.3 analysis software. Results The final analyses included a total of 21 studies and 1907 participants, including 764 NICL-positives and 1143 NICL-negatives. Determinants for NICL-positivity were age (mean deviation (MD): 2.60; 95% confidence interval (CI): [1.53-3.68]), symptomatic carotid lesions (odds ratio (OR): 1.77; 95% CI: [1.39-2.25]) and smoking (OR: 0.74; 95% CI: [0.58-0.94]). For symptomatic patients, risk factors for NICL-positive included diabetes mellitus (OR: 1.76; 95% CI: [1.09-2.82]), but smoking (OR: 0.54; 95% CI: [0.31-0.93]) was a protective factor. Risk factors for centers with high NICL incidence were age (MD: 2.05; 95% CI: [0.93-3.17]) and symptomatic carotid lesions (OR: 1.77; 95% CI: [1.29-2.45]). Conclusions Older age and symptomatic carotid lesions are associated with an increased risk of post-CAS NICL whereas smoking is associated with a decreased risk. Risk factors for NICL in symptomatic patients is diabetes mellitus, while those for patients at centers with high incidence are age and symptomatic carotid lesions. Systematic review registration: CRD42019121129

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease worldwide. It can be transmitted from person to person, and the fatality rate is very high. During this study, three SFTS clusters including 12 associated cases were identified in three counties in Zhejiang Province from 2018 to 2020. The median age of the three index patients was 70 years, and that of secondary case patients was 59 years. Of note, the mortality rate of the index patients was 100%. The mortality rate of secondary case patients was 11%. The total secondary attack rate (SAR) was 30% (9/30). The SARs of cluster A, cluster B, and cluster C were 38% (3/8), 21% (3/14), and 38% (3/8), respectively. Additionally, the interval from onset to diagnosis was 4 days. The intervals from disease onset to confirmation of the index cases and secondary cases were 7 days and 4 days, respectively. All secondary case patients had a history of close contact with blood or body fluids of the index patients. These results indicate that SFTS patients should not be discharged until recovery. When SFTS patients die, the corpses should be transferred directly from the hospital to the crematorium for cremation by persons wearing proper protective equipment to prevent virus transmission.

Objective This study investigates the mismatch between the National Institutes of Health Stroke Scale (NIHSS) score and the computed tomography (CT) findings measured by the Alberta Stroke Program Early CT Score (ASPECTS) for predicting the functional outcome and safety of intravenous thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS). Methods This prospective observational study includes patients with AIS who underwent CT imaging within 4.5 h of the onset of symptoms. Patients were divided into the NIHSS–ASPECTS mismatch (NAM)-positive and NAM-negative groups (group P and N, respectively). The clinical outcome was assessed using the Modified Rankin Scale (mRS). Safety outcomes included progression, symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), adverse events, clinical adverse events, and mortality. Results A total of 208 patients were enrolled in the study. In group P, IVT treatment was associated with a good functional outcome at 3 months (p = 0.005) and 1 year (p = 0.001). A higher percentage of patients with favorable mRS (0–2) (p = 0.01) and excellent mRS (0–1) (p = 0.011) functional outcomes was obtained at 1 year in group P with IVT treatment. Group N did not benefit from the same treatment (p = 0.352 and p = 0.480 at 3 months and 1 year, respectively). There were no statistically significant differences in sICH, ICH, mortality rates, or other risks between the IVT and conventional treatment groups. Conclusion IVT treatment is associated with a good functional outcome in patients with NAM, without increasing the risks of sICH, ICH, mortality, or other negative outcomes. NAM promises to be an easily obtained indicator for guiding the treatment decisions of AIS.

Background. Depression is a common mental disease that lacks effective therapeutic drugs with good curative effects and few adverse reactions. Traditional Chinese medicine (TCM) has the advantages of multiple components, multiple channels, and fewer adverse reactions in the treatment of depression. Although Xingpi Jieyu Decoction (XPJYD) demonstrates a good therapeutic effect on depression, the pharmacological mechanism underlying its antidepressant effect is still unclear. Methods. We used a network pharmacology strategy, including the construction and analysis of a complex drug-disease network, to explore the complex mechanism of XPJYD treatment of depression. In addition, molecular docking technology was used to preliminarily study the binding ability of the potential active components and core therapeutic targets of XPJYD. Results. The network pharmacology results showed 42 targets of XPJYD that are involved in depression. PPI network analysis demonstrated that the top 10 core targets were AKT1, VEGFA, MAPK8, FOS, ESR1, NR3C1, IL6, HIF1A, NOS3, and AR. The molecular docking results showed that the binding energies of beta sitosterol with AR, FOS, AKT1, VEGFA, NR3C1, and NOS3 were less than −7.0 kcal·mol−1, indicating a good docking effect. The GO enrichment analysis results showed that the XPJYD antidepression mechanism mainly involves the following biological processes such as apoptotic signaling pathway, cellular response to lipid, inflammatory response, and others. The KEGG analysis results indicated that XPJYD may regulate 13 pathways such as PI3K-Akt signaling pathway and estrogen signaling pathway in the treatment of depression. Conclusions. This study reflects the characteristics of the mechanism of action by which XPJYD treats depression, which includes multiple components, multiple targets, and multiple pathways, and provides a biological basis for further verification and a novel perspective for drug discovery in depression.

Contemporary treatments for spinal cord arteriovenous shunts are only based on clinicians’ treatment experiences and expertise due to its rarity. We reviewed the clinical course of the largest multicentred cohort to evaluate the efficacy and deficiency of contemporary interventional treatments for spinal cord arteriovenous shunts. The clinical features, treatment results and clinical outcomes of 463 patients with spinal cord arteriovenous shunts were retrospectively assessed. The main outcome was the neurological deterioration that was evaluated based on the modified Aminoff and Logue scale. According to post-treatment digital subtraction angiography, complete obliteration was defined as disappearance of the intradural lesion, whereas partial obliteration was defined as any residual intradural lesion remaining visible and was further categorized as shunt-reduction obliteration (the nidus or shunt points were reduced) or palliative obliteration (only obliterated aneurysms or feeders). Cure rate was 40.6% for the whole cohort, 58.5% after microsurgery, and 26.4% after embolization. The curative resection was associated with non-metameric lesions, lesions with a maximum diameter Although clinical risks of spinal cord arteriovenous shunts were reduced following clinical interventions, contemporary treatments for spinal cord arteriovenous shunt remains associated with considerable risks and incomplete efficacy. Individualized treatment plans should be adopted according to the angio-architectural features and major clinical risks of specific lesions. There is a higher opportunity for complete obliteration for lesions with simple angio-architecture. However, for most of spinal cord arteriovenous shunts with complex vascular anatomy, partial treatment is the only choice. For these patients, palliative obliteration targeting the aneurysms is recommended for reducing haemorrhagic risk, whereas shunt-reduction obliteration is necessary for non-haemorrhagic myelopathy. Contemporary treatment is ineffective in reducing haemorrhagic risk of incurable metameric spinal cord arteriovenous shunts.

Pentafluorosulfanyl chloride (SF5 Cl) is the most prevalent reagent for the incorporation of SF5 group into organic compounds. However, the preparation of SF5 Cl often relies on hazardous reagents and specialized apparatus. Herein, we described a safe and practical synthesis of a bench-stable and easy-to-handle solution of SF5 Cl in n-hexane under gas-reagent-free conditions. The synthetic application of SF5 Cl was demonstrated through the unprecedented reaction with diazo compounds. The chemoselective hydro- and chloropentafluorosulfanylations of α-diazo carbonyl compounds were developed in the presence of K3 PO4 or copper catalyst, respectively. These reactions provide a direct and efficient access to various α-pentafluorosulfanyl carbonyl compounds of high value for potential applications.

Since the outbreak of COVID-19 in December 2019 in Wuhan, Zhejiang has become the province with the largest number of cases. The aim of this article is to present Zhejiang province’s experience of establishing an accurate and smart control mechanism for epidemic prevention and control and resumption of work and production using a ‘five-colour epidemic chart’. The number of confirmed cases, proportion of local cases, and occurrence of clustered outbreaks were used as evaluation indicators to calculate the county-level epidemic risk and were assigned different weight coefficients; the absence of cases for 3 and 7 consecutive days was used as the adjustment index. When the first chart was published on February 9, there were 1 very-high-risk, 12 high-risk, and 12 low-risk counties. Under the five-colour chart, Zhejiang began to adopt precise measures to prevent and control the epidemic and resume work and production. By February 24, the low-risk counties had expanded to 82, with no high-risk and very-high-risk counties. The epidemic situation in Zhejiang province has been effectively controlled. The experience of epidemic prevention and control in Zhejiang is worthy to be emulated and learned by other countries and regions.

Uveal melanoma is the most common primary intraocular tumour in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. (−)-4-O-(4-...

Cholesterol gallstones account for over 80% of gallstones, and the pathogenesis of gallstone formation involves genetic and environmental factors. However, data on the evolution of cholesterol gallstones with various densities are limited. This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones. The relative abundance of microbiota in gallbladder tissues was detected. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1, MUC2, MUC3a, MUC3b, MUC4, MUC5ac and MUC5b in gallbladder tissues and bile. The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.A total of 23 patients with gallbladder stones were included. The density of gallstones in the isodense group was significantly lower than that of the calcified group (34.20 ± 1.50 vs. 109.40 ± 3.84 HU, P0.0001). Compared to the isodense group, the calcified group showed a higher abundance of gram-positive bacteria at the fundus, in the body and neck of gallbladder tissues. The concentrations of MUC1, MUC2, MUC3a, MUC3b, MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups, while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus (15.49 ± 0.69 vs. 10.23 ± 0.54 ng/mL, P0.05), in the body (14.54 ± 0.94 vs. 11.87 ± 0.85 ng/mL, P0.05) as well as in the neck (14.77 ± 1.04 vs. 10.85 ± 0.72 ng/mL, P0.05) of gallbladder tissues. Moreover, the abundance of bacteria was positively correlated with the expression of MUC4 (r = 0.569, P0.05) in the calcified group.This study showed the potential clinical relevance among biliary microbiota, mucins and calcified gallstones in patients with gallstones. Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.

Objective This study aim to analyse the prevalence, clinical pattern and management of orofacial Infection in Hospital Sultan Abdul Halim (HSAH), Kedah, Malaysia. We also investigate any associations between demographic factors, diabetic status, smoking status, and number of space involvement towards the length of hospital stay. Material and methods All adult patients with orofacial infections who attended the Oral and Maxillofacial Department in HSAH from January 2015 to January 2019 were included. Descriptive statistical analysis was done for all variables. For cases requiring hospitalization, logistics regression analysis was performed using dichotomous dependent variable on length of stay(LOS), namely short stay group (LOS ≤ 5 days) and long stay group (LOS > 5 days). Simple logistic regression was performed to determine which factors are associated with prolonged hospital stay. Results A total of 207 patients (133 male, 74 female) were included in this study with mean age of 33.85 ± 19.36 years. The most common aetiology of orofacial infection was odontogenic (71.0 %). Most of the orofacial spaces involved were single (89.9 %), with the mean number of 1.04 ± 1.391. For inpatient cases, three factors were significantly associated with increased risk of prolonged hospital stay, namely multiple spaced involved (OR 3.492, 95 % 1.132–10.77), presence of diabetes (OR 3.694, 95 % 1.314–10.389), and active smoker (OR 5.029, 95 % 1.894–13.349). Conclusion Our study showed a relatively high prevalence of orofacial infection in this region. Factors such as smoking, diabetes and involvement of multiple spaces are associated with prolonged hospital stay during the treatment of orofacial infection.

Pseudaminic acid (Pse), a unique carbohydrate in surface-associated glycans of pathogenic bacteria, has pivotal roles in virulence. Owing to its significant antigenicity and absence in mammals, Pse is considered an attractive target for vaccination or antibody-based therapies against bacterial infections. However, a specific and universal probe for Pse, which could also be used in immunotherapy, has not been reported. In a prior study, we used a tail spike protein from a bacteriophage (ΦAB6TSP) that digests Pse-containing exopolysaccharide (EPS) from Acinetobacter baumannii strain 54149 (Ab-54149) to form a glycoconjugate for preparing anti-Ab-54149 EPS serum. We report here that a catalytically inactive ΦAB6TSP (I-ΦAB6TSP) retains binding ability toward Pse. In addition, an I-ΦAB6TSP-DyLight-650 conjugate (Dy-I-ΦAB6TSP) was more sensitive in detecting Ab-54149 than an antibody purified from anti- Ab-54149 EPS serum. Dy-I-ΦAB6TSP also cross-reacted with other pathogenic bacteria containing Pse on their surface polysaccharides (e.g., Helicobacter pylori and Enterobacter cloacae), revealing it to be a promising probe for detecting Pse across bacterial species. We also developed a detection method that employs I-ΦAB6TSP immobilized on microtiter plate. These results suggested that the anti-Ab-54149 EPS serum would exhibit cross-reactivity to Pse on other organisms. When this was tested, this serum facilitated complement-mediated killing of H. pylori and E. cloacae, indicating its potential as a cross-species antibacterial agent. This work opens new avenues for diagnosis and treatment of multidrug resistant (MDR) bacterial infections.

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) have been well-established as two effective treatment modalities for carotid artery stenosis, while their clinical outcomes in real-world China are still unknown due to lack of nationwide trials. We aimed to evaluate the safety outcome profile of CEA and CAS in Chinese patients with carotid artery stenosis. The Revascularization of Extracranial Carotid Artery Stenosis trial was a multicentre, prospective cohort study of CEA or CAS in treating patients with carotid artery stenosis. We included symptomatic or asymptomatic patients with carotid artery stenosis (≥ 50%). The primary endpoint was any stroke, myocardial infarction and/or death within 1 month post-procedure. Overall, 2719 cases (1543 CAS-treated patients and 1176 CEA-treated patients) were enrolled from 36 centres. The primary outcome was 4.3% (95% CI 3.2–5.6%) and 4.7% (95%CI 3.5–6.3%) in the symptomatic and asymptomatic patients, respectively. No significant difference in the primary outcome was found between CAS and CEA in both symptomatic (p = 0.338) and asymptomatic (p = 0.890) patients. High- versus low-volume centre significantly related to lower rate of primary outcome in CEA-treated patients (OR 2.54; 95%CI 1.19–5.44; p = 0.017) and asymptomatic patients (OR 2.54; 95%CI 1.42–4.54; p = 0.002). CEA and CAS decided by surgeons’ discretion have comparable risks among patients with carotid artery stenosis in China. Both CEA and CAS should be avoided in asymptomatic patients until a consistently low complication rate is showed with centre-level audits. Medical treatment for patients with carotid stenosis in China needs to be improved. Trial registration: NCT01994187 ( ClinicalTrials.gov ).

To investigate the performance of a knowledge-based RapidPlan, for optimisation of intensity-modulated proton therapy (IMPT) plans applied to hepatocellular cancer (HCC) patients. A cohort of 65 patients was retrospectively selected: 50 were used to “train” the model, while the remaining 15 provided independent validation. The performance of the RapidPlan model was benchmarked against manual optimisation and was also compared to volumetric modulated arc therapy (RapidArc) photon plans. A subanalysis appraised the performance of the RapidPlan model applied to patients with lesions ≤300 cm3 or larger. Quantitative assessment was based on several metrics derived from the constraints of the NRG-GI003 clinical trial. There was an equivalence between manual plans and RapidPlan-optimised IMPT plans, which outperformed the RapidArc plans. The planning dose–volume objectives were met on average for all structures except for D0.5 cm3 ≤30 Gy in the bowels. Limiting the results to the class-solution proton plans (all values in Gy), the data for manual plans vs RapidPlan-based IMPT plans, respectively, showed the following: D99% to the target of 47.5 ± 1.4 vs 47.2 ± 1.2; for organs at risk, the mean dose to the healthy liver was 6.7 ± 3.6 vs 6.7 ± 3.7; the mean dose to the kidneys was 0.2 ± 0.5 vs 0.1 ± 0.2; D0.5 cm3 for the bowels was 33.4 ± 16.4 vs 30.2 ± 16.0; for the stomach was 17.9 ± 19.9 vs 14.9 ± 18.8; for the oesophagus was 17.9 ± 15.1 vs 14.9 ± 13.9; for the spinal cord was 0.5 ± 1.6 vs 0.2 ± 0.7. The model performed similarly for cases with small or large lesions. A knowledge-based RapidPlan model was trained and validated for IMPT. The results demonstrate that RapidPlan can be trained adequately for IMPT in HCC. The quality of the RapidPlan-based plans is at least equivalent compared to what is achievable with manual planning. RapidPlan also confirmed the potential to optimise the quality of the proton therapy results, thus reducing the impact of operator planning skills on patient results.

The aim of this study is to compare the recurrence rates with different modalities used as first-line treatment for first-episode primary spontaneous pneumothorax, and investigated the risk factors for recurrence. We retrospectively reviewed consecutive patients under 60 years of age who were treated for a first episode of primary spontaneous pneumothorax between May 1996 and May 2016 at our hospital. The patients were divided into 6 groups according to the treatment received. A total of 667 patients with 890 episodes of primary spontaneous pneumothorax were included in the analysis. The median follow-up period was 64.5 months. The recurrence rate in the 6 groups was as follows: observation, 52.5% (21/40); chest tube drainage, 32.6% (84/258); aspiration, 100% (42/42); axillary thoracotomy, 8.8% (9/102); 2-port video-assisted thoracoscopic surgery (VATS), 6.0% (7/117); and 3-port VATS, 10.6% (11/108). The recurrence rate was higher in non-surgery groups than in surgery groups (147/340 vs 27/327, P

Background Epidemiological studies have shown that genetic factors are among the causes of schizophrenia. Galanin receptor 1 is an inhibitory receptor of galanin that is widely distributed in the central nervous system. This study mainly explored the relationship between polymorphisms of the 5' region of the GALR1 gene and schizophrenia in the northern Chinese Han population. Methods A 1545 bp fragment of the 5' regulatory region of the GALR1 gene was amplified and sequenced in 289 schizophrenia patients and 347 healthy controls. Results Among the haplotypes composed of the 16 detected SNPs, the haplotype H3 was identified as conferring a risk of schizophrenia (p=0.011, OR=1.430, 95% CI=1.084-1.886). In addition, the haplotypes H4 and H7 were both protective against schizophrenia (p=0.024, OR=0.526, 95% CI=0.298-0.927; p=0.037, OR=0.197, 95% CI=0.044-0.885, respectively). In the subgroup analysis by sex, it was found that seven SNP alleles (rs72978691, rs11662010, rs11151014, rs11151015, rs13306374, rs5373, rs13306375) conferred a risk of schizophrenia in females (p

Silent new ischemic cerebral lesions (sNICL) detected by diffusion-weighted imaging (DWI) are common after carotid artery stenting (CAS). As part of the Revascularization of Extracranial Carotid Artery Stenosis (RECAS) study, this work aimed to determine predictors of sNICL detected by DWI following CAS. A total of 694 patients eligible for the RECAS study treated in Xuanwu Hospital, Capital Medical University, with complete imaging data were included in this retrospective study. The patients were asymptomatic after CAS, and those with stroke, transient ischemic attack (TIA), or death were excluded. The RECAS protocol specified that DWI was completed 1–7 days before the procedure and within 3 days after CAS. Several parameters were assessed for associations with sNICL occurrence after CAS in univariate analysis. Finally, multivariate analysis was performed to determine risk factors for sNICL. The rate of post-procedural sNICL in CAS was 51.3% (356/694 patients with sNICL). All patients underwent stenting with embolic protection devices. Univariate analysis showed that diabetes mellitus (P = 0.008), ipsilateral calcified plaques (P = 0.036), ipsilateral ulcerated plaques (P = 0.026), pre-dilatation (P = 0.003), and open-cell stent use (P

Background Abnormal RGS4 gene expression may cause neurotransmitter disorders, resulting in schizophrenia. The association between RGS4 and the risk of schizophrenia is controversial, and there has been little research on the SNPs in the promoter region of RGS4. Purpose The present study was performed to detect the association between SNPs in the promoter region of the RGS4 gene and the risk of schizophrenia. Materials and Methods In this study, the 1757-bp fragment (-1119-+600, TSS+1) of RGS4 was amplified and sequenced in 198 schizophrenia patients and 264 healthy controls of the northern Chinese Han population. Allele, genotype and haplotype frequencies were analyzed by chi-square test. Results Four SNPs were detected in the region. LD analysis determined that rs7515900 was linked to rs10917671 (D' = 1, r2 = 1). Therefore, the data for rs10917671 were eliminated from further analysis. Genotype TT of rs12041948 (P = 0.009, OR = 1.829, and 95% CI = 0.038-0.766) was significantly different between the two groups in the northern Chinese Han population. In males, genotype GG of rs6678136 (P = 0.009, OR = 2.292, and 95% CI = 1.256-4.18) and CC of rs7515900 (P = 0.003, OR = 2.523, and 95% CI = 1.332-4.778) were significantly different. Conclusion The results of this study suggested that genotype TT of rs12041948 in the pooled male and female samples and GG of rs6678136 and CC of rs7515900 in the male samples could be risk factors for schizophrenia. The present study is the first to detect an association between SNPs in the promoter region of the RGS4 gene and the risk of schizophrenia in the northern Chinese Han population. Functional studies are required to confirm these findings.

OBJECTIVE: To provide clinical management guidelines for novel coronavirus (COVID-19) in pregnancy. METHODS: On February 5, 2020, a multidisciplinary teleconference comprising Chinese physicians and researchers was held and medical management strategies of COVID-19 infection in pregnancy were discussed. RESULTS: Ten key recommendations were provided for the management of COVID-19 infections in pregnancy. CONCLUSION: Currently, there is no clear evidence regarding optimal delivery timing, the safety of vaginal delivery, or whether cesarean delivery prevents vertical transmission at the time of delivery; therefore, route of delivery and delivery timing should be individualized based on obstetrical indications and maternal-fetal status.

Study design A prospective cohort study. Objective We conducted a prospective cohort study to identify the association between steroids and clinical worsening and compare outcomes between patients with and without preoperative steroid administration. Summary of background data Patients with spinal dural arteriovenous fistulas (SDAVFs) often were misdiagnosed and treated with steroids which led to acute worsening. Methods Patients with angiographically confirmed SDAVFs were recruited consecutively between March 2013 and December 2014 in two referral centers. We reviewed the history of all the patients to identify those patients who were treated with steroids before exclusion of the fistulas. Modified Aminoff & Logue scale (mALS) was used to evaluate the spinal cord function at different time points: before and after steroid administration, before operation, and at 1-year follow-up. Paired t tests were used to assess the mALS of patients with steroid administration at different time points. Unpaired t tests and Pearson chi-square test were used to assess differences between patients with and without steroid administration. Results Eighteen patients with (18.2%) and 81 patients without (81.8%) steroid administration were included in this study. At baseline, there were no difference between both patient groups, in regards to age, sex, duration, location of fistula, treatment, and preoperative mALS. Patients without steroid administration, however, had statistically significant better outcome according to their mALS at 1-year follow-up (P Conclusion Steroid administration can induce acute clinical worsening in patients with SDAVFs that may persist despite successful obliteration of the fistula and should thus be avoided. Level of evidence 3.

Background: The abnormal expression Dopamine D1 receptor (DRD1) gives rise to the dysfunction of dopaminergic neurotransmitter and may be associated with the occurrence of schizophrenia. Mi...

Anoectochilus roxburghii and Anoectochilus formasanus are the major species of genus Anoectochilus used in traditional Chinese medicine for their abundant content of flavonoids and some other medicinal constituents. In recent years, their wild resources are gradually exhausted due to over-collection and ecological deterioration. Artificial cultivation and tissue culture are employed to increase production. In this study, the open reading frame, promoter and genomic sequences of the chalcone synthase (CHS) gene were cloned from these two species according to their transcriptome information, and used for expression analysis in response to the induction of phenylalanine, ultraviolet light and NaCl, and its effect investigation on accumulation of flavonoids. The results showed that the expression of the CHS genes was upregulated in response to these inductions and resulted in increasing accumulation of total flavonoids. However, the increased flavonoids induced by phenylalanine and ultraviolet light were mainly allocated into the anthocyanidin branch of flavonoids biosynthesis. Not only did it improved the medicinal value, but might have inhibitory effect on plant growth because of the increased malondialdehyde accumulation. Under the induction of appropriate concentration of NaCl, the medicinal constituents of flavonoids were increased without inhibition to plant growth.

Background K1 capsular polysaccharide (CPS)-associated Klebsiella pneumoniae is the primary cause of pyogenic liver abscesses (PLA) in Asia. Patients with PLA often have serious complications, ultimately leading to a mortality of ~ 5%. This K1 CPS has been reported as a promising target for development of glycoconjugate vaccines against K. pneumoniae infection. The pyruvylation and O-acetylation modifications on the K1 CPS are essential to the immune response induced by the CPS. To date, however, obtaining the fragments of K1 CPS that contain the pyruvylation and O-acetylation for generating glycoconjugate vaccines still remains a challenge. Methods We analyzed the digested CPS products with NMR spectroscopy and mass spectrometry to reveal a bacteriophage-derived polysaccharide depolymerase specific to K1 CPS. The biochemical and biophysical properties of the enzyme were characterized and its crystal structures containing bound CPS products were determined. We also performed site-directed mutagenesis, enzyme kinetic analysis, phage absorption and infectivity studies, and treatment of the K. pneumoniae-infected mice with the wild-type and mutant enzymes. Results We found a bacteriophage-derived polysaccharide lyase that depolymerizes the K1 CPS into fragments of 1–3 repeating trisaccharide units with the retention of the pyruvylation and O-acetylation, and thus the important antigenic determinants of intact K1 CPS. We also determined the 1.46-Å-resolution, product-bound crystal structure of the enzyme, revealing two distinct carbohydrate-binding sites in a trimeric β-helix architecture, which provide the first direct evidence for a second, non-catalytic, carbohydrate-binding site in bacteriophage-derived polysaccharide depolymerases. We demonstrate the tight interaction between the pyruvate moiety of K1 CPS and the enzyme in this second carbohydrate-binding site to be crucial to CPS depolymerization of the enzyme as well as phage absorption and infectivity. We also demonstrate that the enzyme is capable of protecting mice from K1 K. pneumoniae infection, even against a high challenge dose. Conclusions Our results provide insights into how the enzyme recognizes and depolymerizes the K1 CPS, and demonstrate the potential use of the protein not only as a therapeutic agent against K. pneumoniae, but also as a tool to prepare structurally-defined oligosaccharides for the generation of glycoconjugate vaccines against infections caused by this organism.

Background Esophageal gastrointestinal stromal tumors(GISTs) are extremely rare. We sought to determine whether endoscopic treatment can be a viable therapeutic option for esophageal GISTs. Methods A total of 20 cases with histological diagnosis of esophageal GISTs were obtained from our center between 2008 and 2020. Data on the clinicopathological features and treatment were recorded. Results There were 9 males (45%) and 11 females (55%) in this study, with a median age of 56 years. The tumors preferentially occurred in the middle and lower parts of the thoracic esophagus (45 and 40%, respectively). The mean size of the tumors was 2.27 cm and mitotic index was no more than 5/50 high power field (HPF) in all patients. In this study, 11 patients received endoscopic treatment and nine patients underwent surgical resection. Tumors ranged from 0.6 to 4 cm in the endoscopic treatment patients and 0.5 to 7 cm in the surgical patients. There were no significant differences in gender, age, symptoms, tumor location, tumor size, mitotic index, and adjuvant imatinib therapy between the endoscopic treatment group and the surgery group (all p > .05). The Kaplan-Meier curve suggested that there was also no significant difference in disease-free survival between the two groups (p = .264). Conclusions Endoscopic treatment may be an option for the treatment of esophageal GISTs smaller than 5 cm with a mitotic index no more than 5/50 HPF.

Zixi Yang,1 Feng Ling,1 Sibei Ruan,1 Jiajia Hu,2 Mingxi Tang,1 Xingwang Sun,1 Wenbo Long1 1Pathology Department of the First Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Wenbo Long Email wenbolong@swmu.edu.cnBackground and Objective: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood.Methods: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II–IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry.Results: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis.Conclusion: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.Keywords: human glioma, biomarker, correlation analysis, genetic alteration, survival rate

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two most common rheumatic diseases in the world. Although there are standard methods for the diagnosis of both RA and OA, the differentials in some cases are poor. With deepening research, the role of autophagy in maintaining cell homeostasis and thus enabling cells adapt to external environments has become increasingly prominent. Both RA and OA, two diseases with inherent differences in pathogenesis, gradually show differences in autophagy levels. Our study therefore aims to further understand differences in pathogenesis of RA and OA through in-depth studies of autophagy in RA and OA. We also define appropriate autophagy-related markers as recognition indicators. Differences in autophagy levels between RA and OA were found based on analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment (ssGSEA). These differences were mainly caused by 134 differentially expressed genes (DEGs). In two autophagy-related genes, CXCR4 and SERPINA1, there existed significant statistical difference between RA and OA. An autophagy related index (ARI) was thus successfully constructed based on CXCR4 and SERPINA by binary logistic regression of the generalized linear regression (GLR) algorithm. Pearson analysis indicated that the expression of CXCR4, SERPINA1, and ARI were closely correlated with autophagy scores and immune infiltration. Moreover, ARI showed high disease identification through receiver operating characteristic (ROC) analysis (AUCtesting cohort = 0.956, AUCtraining cohort = 0.867). These results were then verified in GSE12021 independent cohort. In conclusion, ARI associated with autophagy and immune infiltration was successfully constructed for accurately identifying OA and RA. The index, thus, has great potential in clinical applications.

Background: Prior prelabor cesarean delivery (CD) was associated with an increase in the risk of placenta previa (PP) in a second delivery, whether it may impact postpartum hemorrhage (PPH) independent of abnormal placentation. This study aimed to assess the risk of PPH stratified by abnormal placentation following a first CD before the onset of labor (prelabor) or intrapartum CD.Methods: This multicenter, historical cohort study involved singleton, pregnant women at 28 weeks of gestation or greater with a CD history between January 2017 and December 2017 in 11 public tertiary hospitals within 7 provinces of China. PPH was analyzed in the subsequent pregnancy between women with prior prelabor CD and women with intrapartum CD. Furthermore, PPH was analyzed in pregnant women stratified by complications with PP alone [without placenta accreta spectrum (PAS) disorders], complications with PP and PAS, complications with PAS alone (without PP), and normal placentation. We performed multivariate logistic regression to calculate adjusted odds ratios (aOR) and 95% CI controlling for predefined covariates.Results: Out of 10,833 pregnant women, 1,197 (11%) women had a history of intrapartum CD and 9,636 (89%) women had a history of prelabor CD. Prior prelabor CD increased the risk of PP (aOR 1.91, 95% CI 1.40–2.60), PAS (aOR 1.68, 95% CI 1.11–2.24), and PPH (aOR 1.33, 95% CI 1.02–1.75) in a subsequent pregnancy. After stratification by complications with PP alone, PP and PAS, PAS alone, and normal placentation, prior prelabor CD only increased the risk of PPH (aOR 3.34, 95% CI 1.35–8.23) in a subsequent pregnancy complicated with PP and PAS.Conclusion: Compared to intrapartum CD, prior prelabor CD increased the risk of PPH in a subsequent pregnancy only when complicated by PP and PAS.

OBJECTIVE: The purpose of this review is to clarify the potential roles of forkhead box transcription factor M1 (FoxM1) in the occurrence and progression of breast cancer, as well as the predictive value of FoxM1 as a prognostic biomarker and potential therapeutic target for breast cancer. BACKGROUND: Breast cancer, well-known as a molecularly heterogeneous cancer, is still one of the most frequently diagnosed malignant tumors among females worldwide. Tumor recurrence and metastasis are the central causes of high mortality in breast cancer patients. Many factors contribute to the occurrence and progression of breast cancer, including FoxM1. FoxM1, widely regarded as a classic proliferation-related transcription factor, plays pivotal roles in the occurrence, proliferation, invasion, migration, drug resistance, and epithelial-mesenchymal transition (EMT) processes of multiple human tumors including breast cancer. METHODS: The PubMed database was searched for articles published in English from February 2008 to May 2021 using related keywords such as “forkhead box transcription factor M1”, “human breast cancer”, “FoxM1”, and “human tumor”. About 90 research papers and reports written in English were identified, most of which were published after 2015. These papers mainly concentrated on the functions of FoxM1 in the occurrence, development, drug resistance, and treatment of human breast cancer. CONCLUSIONS: Considering that the abnormal expression of FoxM1 plays a significant role in the proliferation, invasion, metastasis, and chemotherapy drug resistance of breast cancer, and its overexpression is closely correlated with the unfavorable clinicopathological characteristics of breast tumor patients, it is considerably important to comprehend the regulatory mechanism of FoxM1 in breast cancer. This will provide strong evidence for FoxM1 as a potential biomarker for the targeted treatment and prognostic evaluation of breast cancer patients.

Importance Much remains unknown about the transmission dynamics of COVID-19. How the severity of the index case and timing of exposure is associated with disease in close contacts of index patients with COVID-19 and clinical presentation in those developing disease is not well elucidated. Objectives To investigate the association between the timing of exposure and development of disease among close contacts of index patients with COVID-19 and to evaluate whether the severity of the index case is associated with clinical presentation in close contacts who develop COVID-19. Design, Setting, and Participants This study used a large, population-based cohort of 730 individuals (index patients) who received a diagnosis of COVID-19 in Zhejiang Province, China, from January 8 to July 30, 2020, along with a contact tracing surveillance program. Field workers visited 8852 close contacts of the index patients and evaluated them for COVID-19 through August 2020. A timeline was constructed to characterize different exposure periods between index patients and their contacts. Main Outcomes and Measures The primary outcome was the attack rate of COVID-19, defined as the total number of new COVID-19 cases diagnosed among contacts of index patients divided by the total number of exposed contacts. A secondary outcome was asymptomatic clinical presentation among infected contacts. Relative risks were calculated to investigate risk factors for COVID-19 among contacts and asymptomatic clinical presentation among infected contacts. Results Among 8852 close contacts (4679 male contacts [52.9%]; median age, 41 years [interquartile range, 28-54 years]) of 730 index patients (374 male patients [51.2%]; median age, 46 years [interquartile range, 36-56 years]), contacts were at highest risk of COVID-19 if they were exposed between 2 days before and 3 days after the index patient’s symptom onset, peaking at day 0 (adjusted relative risk [ARR], 1.3; 95% CI, 1.2-1.5). Compared with being exposed to an asymptomatic index patient, the risk of COVID-19 among contacts was higher when they were exposed to index patients with mild (ARR, 4.0; 95% CI, 1.8-9.1) and moderate (ARR, 4.3; 95% CI, 1.9-9.7) cases of COVID-19. As index case severity increased, infected contacts were less likely to be asymptomatic (exposed to patient with mild COVID-19: ARR, 0.3; 95% CI, 0.1-0.9; exposed to patient with moderate COVID-19: ARR, 0.3; 95% CI, 0.1-0.8). Conclusions and Relevance This cohort study found that individuals with COVID-19 were most infectious a few days before and after symptom onset. Infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that quantity of exposure may be associated with clinical presentation in close contacts.

Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantavirus which was endemic Zhejiang Province, China. In this study, we aim to explore the changing epidemiology of HFRS in Zhejiang, identify high-risk areas and populations, and evaluate relevant policies and interventions to better improve HFRS control and prevention. Methods Surveillance data on HFRS during 1963–2020 in Zhejiang Province were extracted from Zhejiang Provincial Center for Disease Control and Prevention archives and the Chinese Notifiable Disease Reporting System. The changing epidemiological characteristics of HFRS including seasonal distribution, geographical distribution, and demographic features, were analyzed using joinpoint regression, autoregressive integrated moving average model, descriptive statistical methods, and Spatio-temporal cluster analysis. Results From 1963 to 2020, 114 071 HFRS cases and 1269 deaths were reported in Zhejiang Province. The incidence increased sharply from 1973 and peaked in 1986, then decreased steadily and maintained a stable incidence from 2004. HFRS cases were reported in all 11 prefecture-level cities of Zhejiang Province from 1963 to 2020. The joint region (Shengzhou, Xinchang, Tiantai, and surrounding areas), and Kaihua County are the most seriously affected regions throughout time. After 1990, the first HFRS incidence peak was in May-June, with another one from November to January. Most HFRS cases occurred in 21- (26.48%) and 30- years group (24.25%) from 1991 to 2004, but 41- (25.75%) and 51-years (23.30%) had the highest proportion from 2005 to 2020. Farmers accounted for most cases (78.10%), and cases are predominantly males with a male-to-female ratio of 2.6:1. It was found that the median time from onset to diagnosis was 6.5 days (IQR 3.75–10.42), and the time from diagnosis to disease report was significantly shortened after 2011. Conclusions We observed dynamic changes in the seasonal distribution, geographical distribution, and demographic features of HFRS, which should be well considered in the development of control and prevention strategies in future. Additional researches are warranted to elucidate the environmental, meteorological, and social factors associated with HFRS incidence in different decades., Author summary This study conducted a long-term and systematic study on the epidemiological characteristics of HFRS in Zhejiang Province from 1963 to 2020 through a combination of time and space analysis and epidemiology, aiming to analyze the distribution characteristics of HFRS and explore the high incidence of epidemics in Zhejiang Province Regional influence. From 1963 to 2020, all 11 prefecture-level cities in Zhejiang Province reported HFRS cases, and the morbidity and mortality rates decreased significantly. However, the geographical distribution of endemic areas has been expanding to eastern Zhejiang Province. Moreover, the age of high-risk groups increases over time. Although the incidence rate has declined in recent years, HFRS is still a huge threat to people’s health. As the incidence rate changes, some epidemiological characteristics have also changed. Comprehensive interventions should also be adjusted, including rodent control in endemic areas, health education, vaccination, and improved detection and diagnosis capabilities for HFRS epidemiological changes.

Due to constantly emerging new studies on Xuesaitong injection (XST) agent, it is necessary to summarize and analyze the latest published clinical research data to re-evaluate the clinical efficacy and safety of XST. This study mainly aimed to evaluate the clinical efficacy and safety of XST combined with western medicines (WM) for ischemic stroke treatment.The related databases were searched to collect all randomized controlled trials (RCTs) comparing the combination of XST and WM with WM alone for the treatment of patients with ischemic stroke. Participant, intervention, comparison, outcome and study type (PICOS) was the inclusion criteria of all studies. The search for and data extraction of the included studies was performed by 2 researchers, who then conducted quality evaluation. The Cochrane Collaboration's risk of bias tool was used for the article evaluation. The software RevMan 5.3 and Stata 15.0 were used for pooled analysis.A total of 12 RCTs were included involving 1,769 patients with ischemic stroke, which combined XST with WM therapy. Moreover, the funnel plot showed that there was no obvious publication bias in the included studies. Meta-analysis showed that the total effective rate in the XST combined with WM group was higher than that in the WM alone group [odds ratio (OR) =4.04, 95% confidence interval (CI): 2.86 to 5.73, P0.001]. The National Institutes of Health Stroke Scale (NIHSS) score in the XST combined with WM group was significantly lower than that in the WM alone group [weighted mean difference (WMD) =-3.17, 95% CI: -4.14 to -2.20, P0.001]. In addition, XST combined with WM significantly reduced the plasma viscosity, fibrinogen level, whole blood high shear viscosity, and whole blood low shear viscosity in patients with ischemic stroke (P0.01). For the comparison of adverse reactions, the results showed that the adverse reactions among patients with ischemic stroke in the XST combined with WM group and in the WM group did not differ significantly.Compared with single WM medication, XST combined with WM improves the total clinical effective rate, promotes the recovery of patients' neurological function, and has few adverse reactions and high safety in clinical application.

Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.Trial Registration NumbersNCT 03423992

ObjectiveAge-dependent asymptomatic and symptomatic transmission dynamics of COVID-19 have not been well quantified due to limited data. MethodsThrough a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. ResultsThe difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.72% lower transmissibility rate than symptomatic cases, and 74.10% (95%CI: 65.85% - 80.72%) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.22% (95%CI: 22.97% - 34.56%). Simulation showed that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate the spreading. ConclusionAsymptomatic COVID-19 cases play a significant role in transmission. Vaccine Strategies prioritizing the population between 30-60 years old are likely to have the most population-level benefits.

Aim To investigate nurses' core emergency competencies for handling the coronavirus disease-19 (COVID-19) and analyse the factors associated with those competencies. Background COVID-19 has become a major global public health event. Nursing staff have played an important role in COVID-19 prevention and control. Understanding their emergency competencies for handling COVID-19, and the potential disadvantages will help governments to develop targeted training policies and improve nurses' capacities in relation to pandemics and emergency preparedness. Introduction COVID-19 is a disastrous infectious disease, but the competencies of nurses in China to handle COVID-19 have not been well documented. Methods We conducted a cross-sectional survey on nurses from 22 provinces of China in February 2020. The scores of self-report questionnaires were used to analyse their competencies for core emergency care, and linear regression analysis was used to explore influential factors. Results A total of 2570 nurses participated. The study revealed that nurses had a good grasp of COVID-19 knowledge, but the majority of nurses lacked experience in isolation ward work and emergency training. We found that age, professional title, work department, major work content, total work time, disaster rescue history, emergency training and infectious disease training were associated with core emergency competencies. Conclusions Chinese nurses were qualified for handling COVID-19 but still need to strengthen the accumulation of practical experience. Implications for nursing Nurses should actively participate in emergencies to strengthen their operational capacity, whether in training or actual practice. Implications for nursing/health policy Managers should improve relevant policies to ensure that nurses have more opportunities to participate in the practical training of health emergencies and explore effective training methods to improve the ability of nurses to respond to these.

Background Avian influenza A H7N9 (A/H7N9) is characterized by rapid progressive pneumonia and respiratory failure. Mortality among laboratory-confirmed cases is above 30%; however, the clinical course of disease is variable and patients at high risk for death are not well characterized. Methods We obtained demographic, clinical, and laboratory information on all A/H7N9 patients in Zhejiang province from China Centers for Disease Control and Prevention electronic databases. Risk factors for death were identified using logistic regression and a risk score was created using regression coefficients from multivariable models. We externally validated this score in an independent cohort from Jiangsu province. Results Among 305 A/H7N9 patients, 115 (37.7%) died. Four independent predictors of death were identified: older age, diabetes, bilateral lung infection, and neutrophil percentage. We constructed a score with 0–13 points. Mortality rates in low- (0–3), medium- (4–6), and high-risk (7–13) groups were 4.6%, 32.1%, and 62.7% (Ptrend < .0001). In a validation cohort of 111 A/H7N9 patients, 61 (55%) died. Mortality rates in low-, medium-, and high-risk groups were 35.5%, 55.8, and 67.4% (Ptrend = .0063). Conclusions We developed and validated a simple-to-use, predictive risk score for clinical use, identifying patients at high mortality risk.

Although photodynamic therapy has been extensively studied in recent years and preclinical studies have shown promising results, strategies for enhancing PDT outcomes and reducing side effects still urgently need to be developed. In this study, a series of Tamoxifen-zinc(II) phthalocyanine conjugates have been designed and synthesized. In these “double-headed” conjugates, photodynamic therapy agent zinc(II) phthalocyanine and hormone therapy drug Tamoxifen were combined via oligoethylene glycol linkers. The conjugates show high specificity, and some of them show cytotoxic effects against the MCF-7 cells overexpressed Estrogen receptor, due to the targeting and cytostatic Tamoxifen moiety. Upon illumination, all these conjugates show high cytotoxicity due to the photosensitizing phthalocyanine unit. Their structure-activity relationship was also assessed. The results show that [Formula: see text]-substituted Tamoxifen-zinc(II) phthalocyanine conjugates are highly promising anticancer targeting agents which exhibit additive effects of photodynamic therapy and hormone therapy.

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular diseases, there is significant demand for small diameter (inner diameter6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aorta (DRA). However, histological assessments of these grafts revealed the development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of these grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellularized vascular graft to fabricate a RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with a drug delivery function to prevent intimal hyperplasia. RM-HTEV possessed superior mechanical properties compared to DRA and exhibited a sustained drug release profile. To evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was performed on rats. Doppler sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of explanted grafts 12 weeks postimplantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV, without impairing reendothelialization and M2 macrophage polarization. Overall, RM-HTEV represents a promising strategy for developing small-diameter vascular grafts with great clinical translational potential. STATEMENT OF SIGNIFICANCE: In this study, a new type of rapamycin-loaded hybrid tissue-engineered vascular graft (RM-HTEV) was fabricated using electrospinning technology. The unique hybrid bi-layer structure endowed the RM-HTEV with multi-functionality: the exterior rapamycin-loaded electrospun PCL nanofibrous layer enhanced the mechanical properties of the graft and possessed drug releasing property; the interior decellularized aorta layer with porous structure could facilitate cell proliferation and migration. In in vivo implantation experiment, RM-HTEV exhibited satisfying long-term patency rate and significantly inhibited intimal hyperplasia without impairing re-endothelialization and M2 macrophage polarization. This strategy is expected to be a promising strategy for developing bioactive small-diameter vascular grafts with great clinical translational potential.

BACKGROUND No prior reports have focused on the natural history and long-term outcomes of intramedullary spinal cord cavernous malformations (ISCCMs) in children. OBJECTIVE To investigate the clinical characteristics and long-term outcomes of pediatric ISCCMs and identify the risk of hemorrhage. METHODS We retrospectively reviewed a series of 20 pediatric patients (