Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.

Objective To establish a method for the simultaneous determination of aconitine,neoaconitine,hypaconitine,benzoyl aconitine,benzoyl mesaconine and benzoylhypacoitine in Xiaozhong ointment by UPLC-TQD-MS.Methods ACQUITY UPLC BEH C18 column(50 mm ×2.1 mm,1.7 μm),mobile phase 0.1％formic acid water(A)-acetonitrile(B),gradient elution,column temperature 40 ℃,flow rate 0.3 mL·min-1,injection volume 5 μL;electrospray ionization source(ESI+)and multiple reaction monitoring(MRM)were used for mass spectrometry analysis.Results The concentration of aconitine,new aconitine,hypaconitine,benzoyl aconitine,benzoyl new aconitine and benzoyl hypaconitine were 1.0-100.0 ng·mL-1,respectively,the average recovery were 98.62％-101.24％.The mass fractions of the six components were 0.18,0.33,0.38,0.43,0.28,0.06μg·g-1.Conclusion The method can be used to determine the content of 6 aconitine-type alkaloids in Xiaozhong ointment,and provide reference for the quality evaluation and clinical safe use of Xiaozhong ointment.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

Conjugated oligomers,as analogues of conjugated polymers,allow for constructing ultrafine fluorescent nanoparticles with improved sensing sensitivity due to their more precisely defined molecular structure and smaller size.Herein,a new porphyrin-pyridyl conjugated oligomer,i.e.,Zn-TPP-OMe,was designed and synthesized via Sonogashira coupling strategy and a super-small(～2.0 nm)water-soluble fluorescent nanoprobe(Zn-TPP-OMe nanoparticles(NPs))was subsequent obtained by nanoprecipitation method.Due to the addition reaction of chlorine atom to porphyrin ring,the fluorescence intensity of Zn-TPP-OMe NPs at 619-660 nm significantly decreased with increasing HCLO concentration.Meanwhile,Zn-TPP-OMe NPs aggregated obviously after adding HClO,achieving enhanced fluorescence quenching.The fluorescence detection mechanism was verified by transmission electron microscopy(TEM),proton nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS)analyses.The experimental results indicated that the porphyrin-pyridyl conjugated oligomer nanosystem had high sensitivity(LOD=0.005 μmol/L)and excellent selectivity in detection of HClO,and was successfully applied to the sensing of HClO in actual water samples.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To analyze the influencing factors for the knowledge level,cognition willingness and atti-tude of health care workers(HCWs)towards monkeypox.Methods A cross-sectional survey was conducted,from January to April 2023,700 HCWs were randomly selected from a tertiary hospital in Shanghai.Based on a self-de-signed questionnaire,the survey was conducted anonymously through the online platform"Wenjuanxing".Results A total of 612 questionnaires were collected,581 were valid,with a response rate of 87.43％and an effective rate of 94.93％.The mean score of the questionnaire was(128.80±27.70)points,with a score rate of 58.54％.Multiple linear regression analysis showed that there were statistically significant differences in the knowledge level of mon-keypox among HCWs of different ages,occupations,departments,educational levels,years of working experience,professional titles,initiative cognition on monkeypox,and participation in monkeypox-related lectures organized by the units(all P＜0.05).Conclusion HCWs'cognition on monkeypox is at a moderate level.The training of HC-Ws on monkeypox knowledge should be strengthened to improve the emergency response capabilities during mon-keypox outbreaks.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective:To explore the effect of shikonin on autophagy and apoptosis of human promyelocytic leukemia cells and its possible mechanism.Methods:Human promyelocytic leukemia cells NB4 in the logarithmic growth phase were divided into control group(untreated NB4 cells),shikonin group(0.3 μmol/L shikonin treatment),740Y-P group(15 μmol/L PI3K/Akt/mTOR pathway activator 740Y-P treatment),shikonin+740Y-P group(0.3 μmol/L shikonin and 15 μmol/L 740Y-P co-treatment),after 24 hours of treatment,the cells were used for subsequent experiments.CCK-8 method was used to detect cell viability,monodansylcadaverine(MDC)staining to detect the aggregation of autophagic vesicles,flow cytometry to detect cell apoptosis,and Western blot to detect the expression of Beclinl,LC3,p62,Bax,cleaved caspase-3,Bcl-2 and PI3K/Akt/mTOR pathway related proteins.Results:Compared with the control group,the purple punctate fluorescence intensity,apoptosis rate,Beclinl,LC3-Ⅱ/LC3-Ⅰ,cleaved caspase-3,and Bax protein expression in NB4 cells were increased in the shikonin group,while OD450 value(24,48 h)and the expressions of Bcl-2 and p62 proteins were decreased(all P＜0.05).Compared with the control group,the purple punctate fluorescence intensity,apoptosis rate,Beclin1,LC3-Ⅱ/LC3-1,cleaved caspase-3,and Bax protein expression in NB4 cells were decreased,while OD450 value(24,48 h)and the expressions of Bcl-2 and p62 proteins were increased in the 740Y-P group(all P＜0.05).Compared with the shikonin group,the purple punctate fluorescence intensity,apoptosis rate,Beclinl,LC3-Ⅱ/LC3-1,cleaved caspase-3,and Bax protein expression in NB4 cells were decreased,while OD450 value(24,48 h)and the expressions of Bcl-2 and p62 proteins were increased in the shikonin+740Y-P group(all P＜0.05).Compared with the control group,the expression of PI3K/Akt/mTOR pathway related proteins p-PI3K,p-Akt,and p-mTOR in NB4 cells were significantly decreased in the shikonin group,while those in the 740Y-P group were increased(all P＜0.05).Compared with the shikonin group,the expressions of p-PI3K,p-Akt,and p-mTOR proteins in NB4 cells were significantly increased in the shikonin+740Y-P group(all P＜0.05).Conclusion:Shikonin may promote autophagy and apoptosis of NB4 cells by inhibiting PI3K/Akt/mTOR pathway.

Cancer stem cell(CSC)are the"seed"cells in the occurrence,development,metastasis and recurrence of colorectal cancer.Targeted killing of CSC provides a new target for anti-colorectal cancer therapy.Ferroptosis is an iron-dependent cell death mode due to the abnormal accumulation of intracellular i-ron ions,which results in the massive reactive oxygen species(ROS)and lipid peroxides,leading to cell death.Studies have shown that cancer stem cells are more enriched in iron ions than non-CSC,which provides a new perspective for targeting ferropto-sis in cancer stem cells against colorectal cancer.This article re-views the research progress of inducing CSC ferroptosis in the treatment of colorectal cancer,such as targeted regulation of SLC7A11 expression in CSC,chelating iron in CSC lysosomes,targeting CSC phenotypic plasticity,reversing CSC iron homeo-stasis,and targeting CSC lipid droplet metabolism induce CSC ferroptosis,which provides new ideas for anti-tumor therapy.