Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Objective: To study the infection rate of secondary close contacts of COVID-19 patients, and assess the infection risk in the contacts. Methods: COVID-19 patients' close contacts (with a clear exposure time to index case) with negative nucleic acid test results and secondary close contacts were surveyed in continuous isolation and medical observation in this prospective study. The dynamic nucleic acid test results of the close contacts and secondary contacts of COVID-19 patients were collected to assess their risk of infection. Results: A total of 4 533 close contacts were surveyed, in whom 14 were confirmed as COVID-19 patients with overall secondary attack rate of 0.31%, and 4 201 secondary contacts were tracked, in whom no subsequent infections occurred. Conclusion: Close contacts of COVID-19 patients entered in centralized isolation for medical observation with negative nucleic acid tese results,the secondary close contacts of COVID-19 patients have no risk of infection.
COVID-19/epidemiology* ; Contact Tracing ; Humans ; Incidence ; Nucleic Acids ; Prospective Studies ; SARS-CoV-2

OBJECTIVES: To study the difference in cognitive impairment between the children with benign childhood epilepsy with centrotemporal spikes (BECT) and attention deficit hyperactivity disorder (ADHD) and those with BECT or ADHD alone. METHODS: A prospective study was performed on 80 children with BECT and ADHD, 91 children with BECT, and 70 children with ADHD , who were diagnosed with the diseases for the first time. Seventy children of the same age who underwent physical examination were enrolled as the healthy control group. Event-related potential P300, Wechsler Intelligence Scale for Children, and integrated visual and auditory continuous performance test were used to measure and compare each index between groups. RESULTS: Compared with the healthy control group, the BECT+ADHD group, the BECT group, and the ADHD group had a significantly prolonged P300 latency, a significant reduction in the amplitude of P300, and significant reductions in the scores of verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ), auditory response control quotient (ARCQ), visual response control quotient, full response control quotient (FRCQ), auditory attention quotient (AAQ), visual attention quotient, and full attention quotient ( CONCLUSIONS Compared with the children with BECT or ADHD alone, the children with both BECT and ADHD have basically the same fields of cognitive impairment but a higher degree of cognitive impairment in some fields.
Attention Deficit Disorder with Hyperactivity ; Child ; Cognitive Dysfunction/etiology* ; Epilepsy ; Humans ; Prospective Studies ; Wechsler Scales

This paper aims to systematically analyze the peptides and proteins from Asini Corii Colla(ACC) through shotgun proteomics. After high-pH reversed-phase fractionation, the proteins and peptides in the hydrolysate of ACC were further separated by nano LC-Q-Exactive-MS/MS under the following conditions: Thermo Scientific EASY column(100 μm×2 cm, 5 μm, C_(18)) as precolumn, Thermo Scientific EASY column(75 μm×100 mm, 3 μm, C_(18)) for solid phase extraction, gradient elution with 0.1% formic acid in water(mobile phase A) and 84% acetonitrile in water containing 0.1% formic acid(mobile phase B), and MS in positive ion mode. Based on Uniprot_Equus caballus, MS data, and literature, 2 291 peptides were identified from ACC by MaxQuant, with 255 Maillard reactions(AML, CML, CEL)-modified peptides identified for the first time. Through alignment, the peptides were found to belong to 678 equine proteins. In conclusion, the combination of nano LC-Q-Exactive-MS/MS and shotgun proteomics achieved rapid and accurate identification of the proteins and peptides in ACC, which provides the key information and new insights for further investigation of chemicals and effective substances in ACC.
Animals ; Chromatography, Liquid ; Horses ; Peptides ; Proteins ; Proteomics ; Tandem Mass Spectrometry

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

Objective To firstly report the clinical features,diagnosis and treatment response of patients with anti-γ-aminobutyric acid type A receptor (GABAAR) encephalitis in China,thus raising neurologists' awareness of this emerging type of autoimmune encephalitis.Methods Specific anti-GABAAR autoantibodies in the serum and cerebrospinal fluid (CSF) of patients with suspected autoimmune encephalitis but negative for commercial available antibody tests were detected by live cell-based assay (CBA).The clinical features,laboratory examinations and treatment of two cases of autoimmune encephalitis with anti-GABAAR autoantibodies were analyzed,who admitted to Huashan Hospital,Fudan University between 2013 and 2014.Results By using live CBA,serum and CSF of the two patients diagnosed with possible autoimmune encephalitis both contained autoantibodies targeted to the GABAAR.These two patients had onset symptom of seizure or refractory seizures.Memory impairment,psychiatric symptoms and decreased consciousness were also presented.One patient was combined with mass in anterior superior mediastinum.Both patients had multifocal cortical and subcortical T2 /fluid attenuated inversion recovery-weighted images hyperintensity signal on brain magnetic resonance imaging.The two patients had poor response to antiepileptic drugs,but showed noticeable recovery with sufficient immunotherapeutic treatments.Conclusions Anti-GABAAR encephalitis is characterized by prominent epilepsy and multifocal abnormalities on brain magnetic resonance imaging.Autoantibodies specifically against GABAAR could be detected by CBA in this group of patients.Early diagnosis and immunotherapy are critical to improve clinical symptoms and outcomes of the disease.

Objective:To investigate the differences in matrix metalloproteinases (MMPs) and matrix metalloproteinase inhibitors (TIMPs) from diseased splenic vein (DSVs) and varicose great saphenous vein (VGSVs) under high hemodynamics.Methods:Seventy-two specimens of DSVs,normal splenic veins (SVs),VGSVs,and normal great saphenous vein (GSVs) were collected.Venous wall in the four groups,MMP-2,MMP-9,TIMP-1,and TIMP-2 protein expression were observed and MMP-2,MMP-9,TIMP-1,TIMP-2 proteins positive expression ratio and mRNA expression were determined.Results:DSVs and VGSVs in the two groups,MMP-2,MMP-9,TIMP-1,TIMP-2 proteins with clustered strong expression were observed;In DSVs group,MMP-2,MMP-9,TIMP-1,TIMP-2 protein positive expression ratio and mRNA expression were significantly increased compared with SVs group,while in VGSVs group,MMP-2,MMP-9,TIMP-1,TIMP-2 protein positive expression ratio and mRNA expression were significantly increased compared with GSVs group (P＜0.05).VGSVs/GSVs ratio was significantly increased compared with DSVs/SVs ratio (P＜0.05).Conclusion:Under high hemodynamics,the dysequilibrium of MMPs and TIMPs from splenic vein and great saphenous vein,These results may be one of the molecular mechanism in vascular remodeling.

BACKGROUNDSome problems have been found in the usually adopted combined approach for the removal of intra-extracranial tumors in skull base. Herein, we described a pure endoscopic transnasal or transoral approach (ETA) for the removal of intra-extracranial tumors in various skull base regions.

METHODSRetrospectively, clinical data, major surgical complications, pre- and postoperative images, and follow-up information of a series of 85 patients with intra-extracranial tumors in various skull base regions who were treated by surgery via ETA in our skull base center during the past 10 years were reviewed and analyzed.

RESULTSGross total tumor removal was achieved in 80/85 cases (94.1%) in this study. All 37 cases with tumors in anterior skull base and all 14 cases with tumors in jugular foramen received total tumor removal. Thirteen and three cases with tumors in clivus received total and subtotal tumor removal, respectively. Total and subtotal tumor removal was performed for 16 cases and 2 cases in lateral skull base, respectively. The complications in this study included: cerebrospinal fluid leakage (n = 3), meningitis (n = 3), and new cranial nerve deficits (n = 3; recovered in 3 months after surgery). In the follow-up period of 40-151 months (median: 77 months), seven patients (8.8%) out of the 80 cases of total tumor removal experienced recurrence.

CONCLUSIONSComplete resection of intra-extracranial growing tumors in various skull base regions can be achieved via the pure ETA in one stage in selected cases. Surgical procedure for radical removal of tumors is feasible and safe.

To prepare tanshinone ⅡA loaded nanostructured lipid carrier (Tan ⅡA-NLC), and study its in vitro transdermal permeation characteristics. The Tan ⅡA-NLC was prepared by high pressure homogenization technology and optimized by Box-Behnken design-response surface method, and it was characterized in terms of morphology, particle size, zeta potention, et al. The transdermal permeation of Tan ⅡA-NLC was evaluated by using Franz diffusion cells. The results showed that, the optimal formulation was as follows: drug/lipid materials ratio 88, GMS/MCT ratio 2, emulsifier concentration 1%, average particle size (182±14) nm, polydispersity index PDI (0.190 6±0.024 5), zeta potential (－27.8± 5.4) mV, encapsulation efficiency EE (86.44%±9.26%) and drug loading DL (0.98%±0.18%), respectively. The in vitro transdermal permeation results showed that as compared with Tan ⅡA solution, Tan ⅡA-NLC had lower transdermal permeation amount after applying drug for 24 h, but its retention in the epidermis was 3.18 times that of solution. These results indicated that the prepared Tan ⅡA-NLC could effectively increase the regention of Tan ⅡA in the epidermis, and had a broad application prospect.

Objective To investigate the safety of peri-operative management on children with juvenile recurrent respiratory papilloma (JORRP).Methods A retrospective analysis was conducted on preoperative assessment,anesthesia methods and options,operative procedure,and postoperative airway maintenance in 28 JORRP children aged from ten months to seven years old.A total of 148 times of surgery was performed on these 28 children.Results One hundred and nine JORRP children graded one and two- degree dyspnea underwent surgery within 24 hours and were intubated successfully in the first attempt after intravenous induction.Thirty-nine emergency operations were performed in the children graded three and four-degree dyspnea,35 of them were intubated successfully in the first attempt after inhalation induction and 4 succeeded in the second attempt.No complications occurred in 129 JORRP children postoperatively,17 children suffered from mild dyspnea and relieved after oxygen inhalation,2 children were intubated and sent to intensive care unit because of postoperative hypoxemia.All JORRP children got through the peri-operative period safely.The quality of pronunciation in 101 children improved markedly and 35 suffered from slight hoarseness on the 1st postoperative day.Three children had the tracheal tube of tracheostomy removed after receiving five,four and three operations respectively.Nineteen children were followed up for 2 -5 years.Among them,one child did not relapse 3 years after surgical management.One child suffered from laryngostenosis postoperatively. No death occurred. Conclusion Complete preoperative preparation,rational anesthesia methods,careful operative procedure and airway maintenance after surgery could increase the safety for children with recurrent respiratory papilloma.