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

This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Abelmoschus/chemistry* ; Macrophages/metabolism* ; Colitis, Ulcerative/immunology* ; Flavones/administration & dosage* ; Male ; Depression/genetics* ; Glycerophospholipids/metabolism* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To investigate the effect of sodium butyrate on apoptosis of rat mesangial cells and the regulation of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signal pathway,and analyze the possible mechanism.Methods Primary cultured,isolated and purified rat mesangial cells.The cells were randomly divided into blank group,control group[10 μg·L-1 epidermal growth factor(EGF)],low dose experimental group(10μg·L-1 EGF+0.5 mmol·L-1 sodium butyrate),medium dose experimental group(10 μg·L-1 EGF+1.0 mmol·L-1 sodium butyrate)and high dose experimental group 10 μg·L-1 EGF+2.0 mmol·L-1sodium butyrate).Cell survival rate was detected by cell counting kit-8(CCK-8)method,cell cycle was detected by propyl iodide(PI)staining,cell apoptosis rate was detected by flow cytometry,and the expression of PI3K/AKT/mTOR channel-related proteins was detected by Western blot.Results After 24 h of treatment,the optical density of blank group,control group and low,medium,high dose experimental group were 0.36±0.03,0.66 ±0.03,0.57±0.05,0.47±0.02,0.41±0.01;which at 48 h of treatment were 0.55±0.03,0.83±0.04,0.68 ±0.03,0.65±0.02,0.60±0.02,respectively.The results showed that 10 μg·L-1 EGF significantly stimulated the proliferation and activation of mesangial cells(P＜0.05),and the proliferation of mesangial cells was significantly inhibited after treatment with different concentrations of sodium butyrate for 24 and 48 h(P＜0.05).PI staining showed that the G1 phase blocking rates of blank group,control group and low,medium,high dose experimental groups were(53.37±0.43)％,(46.84±0.67)％,(57.81±0.48)％,(62.77±0.77)％,(67.57±0.71)％,respectively.The results showed that sodium butyrate could induce cell cycle arrest in G1 phase in a concentration-dependent manner(P＜0.01).The apoptosis rates of blank group,control group and low,medium,high dose experimental groups were(4.43±0.48)％,(2.45±0.31)％,(6.16±0.33)％,(8.25±0.40)％and(12.12±0.41)％,the differences were statistically significant between control group and low,medium,high dose experimental groups(all P＜0.01).Conclusion Sodium butyrate can effectively inhibit the proliferation and induce apoptosis of rat mesangial cells,and its mechanism may be related to the inhibition of PI3K/AKT/mTOR signaling pathway.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Purpose::Terminal performance of a bullet in human body is critical for the treatment of gunshot injury and optimization of bullet design. The effects of the impact velocity ( v0) and the impact attack angle ( δ0) of the bullet on its terminal performance was investigated, using a new evaluation method (called expansion method) based on the expansion of cracks and the permanent cavity wall in ballistic gelatin. Methods::Ballistic gelatin was used to simulate human body. The 7.62 mm × 39 mm rifle bullets with different v0 (600-760 m/s) and δ0 (0°-6°) were fired into the gelatin blocks. The gelatin block was cut into slices of about 20 mm thickness. The cracks and the permanent cavity on each slice were obtained manually. The damaged gelatin was determined using two methods: expanding the permanent cavity but ignoring the cracks, and expanding both the permanent cavity and the cracks. The relations between the damaged gelatin and v0 and δ0 were obtained using linear fitting method. Results::According to the distribution of the damaged gelatin along the penetration depth, the damaged gelatin block could be divided into two parts: the less damaged part and the severely damaged part. The length of the less damaged part depends mostly on δ0; while the average damaged area of this part depends on both δ0 as well as v0. The cracks contributed significantly to the total volume of damaged gelatin, particularly when the expansion was larger than 1.9 mm. The total damaged gelatin increases with v0, δ0 and the expansion extent. The average length of equivalent cracks grew with v0 and δ0 when considering the cracks, and decreased with v0 when ignoring the cracks. Conclusion::The expansion method is suitable to investigate the influence of different factors of bullets on their terminal performance. The characteristics of the damaged gelatin have a linear relationship with the initial attack angle ( δ0) and the initial velocity ( v0) of the bullet.

2019 novel coronavirus(2019-nCoV) outbreak is one of the public health emergency of international concern.Since the 2019-nCoV outbreak, China has been adopting strict prevention and control measures, and has achieved remarkable results in the initial stage of prevention and control.However, some imported cases and sporadic regional cases have been found, and even short-term regional epidemics have occurred, indicating that the preventing and control against the epidemic remains grim.With the change of the incidence proportion and the number of cases in children under 18 years old, some new special symptoms and complications have appeared in children patients.In addition, with the occurrence of virus mutation, it has not only attracted attention from all parties, but also proposed a new topic for the prevention and treatment of 2019-nCoV infection in children of China.Based on the second edition, the present consensus further summarizes the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of treatment of 2019-nCoV infection in children.