Plant-derived exosome-like nanovesicles refer to spherical lipid bilayer vesicles isolated from plants that contain lipids,proteins,RNAs,and various small molecules.These nanovesicles exhibit di-verse biological activities,including anti-inflammatory,anti-tumor,antioxidant,and drug delivery prop-erties.However,the functional characteristics of nanovesicles derived from rhizoma polygonati remain un-explored.In this study,exosome-like nanovesicles derived from rhizoma polygonati(referred to as RP-EVs)were successfully isolated using ultracentrifugation and density gradient centrifugation.Their physi-cochemical properties and anti-inflammatory functions were systematically characterized.Our results show that RP-EVs are predominantly negatively charged,with an average particle size of 166.5±3.3 nm,and are spherical lipid vesicles.Cellular uptake assays demonstrated that RP-EVs can be phagocytized by macrophages.qPCR and ELISA experiments revealed that RP-EVs can inhibit the elevation of interleukin 6(IL-6),interleukin 1 β(IL-1 β),and tumor necrosis factor-alpha(TNF-α)induced by lipopolysac-charide(LPS)stimulation(****P＜0.0001).Additionally,reactive oxygen species(ROS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assays confirmed that RP-EVs exhibit antioxidant proper-ties(*P＜0.05).Further investigation of the underlying mechanisms through immunofluorescence and Western blotting revealed that RP-EVs inhibit the nuclear translocation(**P＜0.01)and phosphoryla-tion(***P＜0.001)of nuclear factor kappa-B p65(NF-κB p65)via the IκBα/NF-κB signaling path-way,thereby regulating the expression of inflammatory mediators.In animal experiments,intraperitoneal injection of RP-EVs into mice for 48 hours showed predominant localization in the liver and spleen.Fi-nally,an acute inflammatory mouse model was established via intraperitoneal injection of LPS.qPCR and ELISA analyses demonstrated that RP-EVs alleviated the expression of inflammatory factors in both the serum and spleen of LPS-treated mice(*P＜0.05).In conclusion,this study isolated RP-EVs and elu-cidated their anti-inflammatory properties and potential mechanisms.These findings provide valuable in-sights into the functional exploration of nanoparticle vesicles derived from traditional Chinese medicine and suggest a novel therapeutic strategy for the treatment of inflammation-related diseases.

OBJECTIVE: To explore clinical efficacy of vancomycin-loaded antibiotic bone cement combined with induced membrane grafting for the treatment of diabetic foot ulcers(DFU). METHODS: Totally 68 DFU patients treated with bone cement combined with induced membrane grafting from November 2019 to November 2021 were retrospectively analyzed, including 37 males and 31 females, aged from 51 to 79 years old with an average of (63.63±7.85) years old;47 patients on the right side and 21 patients on the left side;28 patients with grade 2, 31 patients with were grade 3, and 9 patients with grade 4 according to Wagner's grades;the diameter of the wound ranged from 20.40 to 96.99 mm with an average of (59.67±23.26) mm. The time of wound healing, the number of operations, the survival of postoperative skin grafting, the number of postoperative recurrence and the rate of amputation were observed. RESULTS: All 68 patients were followed up for 12 to 18 months with an average of (15.06±2.12) months. The wound healing time ranged from 42 to 65 d with an average of (51.50±7.24) d, the numbers of operation ranged from 2 to 3 with an average of (2.25±0.44) times. All skin grafts were survived well after operation, without recurrence and amputation cases. CONCLUSION Vancomycin-containing antibiotic bone cement combined with induced membrane grafting is effective in treating DFU, and the operation is simple and reliable.
Humans ; Male ; Female ; Middle Aged ; Vancomycin/therapeutic use* ; Bone Cements/therapeutic use* ; Aged ; Diabetic Foot/therapy* ; Skin Transplantation ; Anti-Bacterial Agents/therapeutic use* ; Retrospective Studies ; Wound Healing/drug effects*

In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

Objective To addresses the challenges arising from the rapid expansion of pharmaceutical clinical trials and the growing demands for quality management,this paper investigates the application of low-code technology in project management.Its goals are to enhance the operational efficiency and execution capabilities of clinical trial institutions,ensure trial quality and safety,and accelerate the translation of pharmaceutical scientific achievements.Methods A brainstorming session was conducted to analyze the technical and functional requirements for managing pharmaceutical clinical trial projects.Utilizing the ＂template design＂ and ＂decision analysis＂ functionalities of low-code technology,the study adopted a modular and visually driven data management approach to develop a system compliant with Good Clinical Practice(GCP)standards.This system integrates key functionalities,including project progress management,funding management,drug inventory management,and quality control.Its effectiveness was evaluated through real-world operation and performance validation.Results The system had demonstrated stable operation with substantial improvements in practical application.Compared with conventional management approaches,it significantly enhanced project management efficiency:the time required for project schedule management was reduced by 80%,the efficiency of financial processing increased by 95%,drug inventory management efficiency improved by 75%,and the time spent on quality control was shortened by 60%.Conclusion The pharmaceutical clinical trial project management system developed using low-code technology offers substantial advantages and promising application potential.It represents a critical practice in applying digital and intelligent tools to advance pharmaceutical productivity in the medical and healthcare sectors.

Objective To addresses the challenges arising from the rapid expansion of pharmaceutical clinical trials and the growing demands for quality management,this paper investigates the application of low-code technology in project management.Its goals are to enhance the operational efficiency and execution capabilities of clinical trial institutions,ensure trial quality and safety,and accelerate the translation of pharmaceutical scientific achievements.Methods A brainstorming session was conducted to analyze the technical and functional requirements for managing pharmaceutical clinical trial projects.Utilizing the ＂template design＂ and ＂decision analysis＂ functionalities of low-code technology,the study adopted a modular and visually driven data management approach to develop a system compliant with Good Clinical Practice(GCP)standards.This system integrates key functionalities,including project progress management,funding management,drug inventory management,and quality control.Its effectiveness was evaluated through real-world operation and performance validation.Results The system had demonstrated stable operation with substantial improvements in practical application.Compared with conventional management approaches,it significantly enhanced project management efficiency:the time required for project schedule management was reduced by 80%,the efficiency of financial processing increased by 95%,drug inventory management efficiency improved by 75%,and the time spent on quality control was shortened by 60%.Conclusion The pharmaceutical clinical trial project management system developed using low-code technology offers substantial advantages and promising application potential.It represents a critical practice in applying digital and intelligent tools to advance pharmaceutical productivity in the medical and healthcare sectors.

Objective This study aimed to investigate natural infection of rodents with Ehrlichia and Neoehrlichia at major Chinese land-border ports along the"Belt and Road".Methods In 2022,rodents were monitored in 10 ports in northern and southern China and identified based on diagnostic morphological characteristics.The 16S rRNA genes of Ehrlichia and Neoehrlichia were detected by PCR using universal primers from rodent samples and phylogenetic analysis was performed based on the sequences of the detected positive pathogens.Results A total of 356 rodents were sampled,including 2 orders,5 families,15 genera,and 20 species.Predominantly,73,61,56,and 58 were Meriones unguiculatus(20.51%),Rattus norvegicus(17.13%),Apodemus agrarius(15.73%),and Microtus gregalis(16.29%).Only one Microtus fortis from Suifenghe Port was infected with Ehrlichia sp.Moreover,12 rodents were infected with Neoehrlichia spp.(overall positivity rate:3.37%).Conclusions Natural infections with Ehrlichia spp.and Neoehrlichia spp.were demonstrated in rodents at important Chinese land-border ports.The positivity rate of Neoehrlichia spp.was high in some ports,indicating that surveillance for ticks and their prevention and control measures should be intensified in these regions.

Plant-derived exosome-like nanovesicles refer to spherical lipid bilayer vesicles isolated from plants that contain lipids,proteins,RNAs,and various small molecules.These nanovesicles exhibit di-verse biological activities,including anti-inflammatory,anti-tumor,antioxidant,and drug delivery prop-erties.However,the functional characteristics of nanovesicles derived from rhizoma polygonati remain un-explored.In this study,exosome-like nanovesicles derived from rhizoma polygonati(referred to as RP-EVs)were successfully isolated using ultracentrifugation and density gradient centrifugation.Their physi-cochemical properties and anti-inflammatory functions were systematically characterized.Our results show that RP-EVs are predominantly negatively charged,with an average particle size of 166.5±3.3 nm,and are spherical lipid vesicles.Cellular uptake assays demonstrated that RP-EVs can be phagocytized by macrophages.qPCR and ELISA experiments revealed that RP-EVs can inhibit the elevation of interleukin 6(IL-6),interleukin 1 β(IL-1 β),and tumor necrosis factor-alpha(TNF-α)induced by lipopolysac-charide(LPS)stimulation(****P＜0.0001).Additionally,reactive oxygen species(ROS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assays confirmed that RP-EVs exhibit antioxidant proper-ties(*P＜0.05).Further investigation of the underlying mechanisms through immunofluorescence and Western blotting revealed that RP-EVs inhibit the nuclear translocation(**P＜0.01)and phosphoryla-tion(***P＜0.001)of nuclear factor kappa-B p65(NF-κB p65)via the IκBα/NF-κB signaling path-way,thereby regulating the expression of inflammatory mediators.In animal experiments,intraperitoneal injection of RP-EVs into mice for 48 hours showed predominant localization in the liver and spleen.Fi-nally,an acute inflammatory mouse model was established via intraperitoneal injection of LPS.qPCR and ELISA analyses demonstrated that RP-EVs alleviated the expression of inflammatory factors in both the serum and spleen of LPS-treated mice(*P＜0.05).In conclusion,this study isolated RP-EVs and elu-cidated their anti-inflammatory properties and potential mechanisms.These findings provide valuable in-sights into the functional exploration of nanoparticle vesicles derived from traditional Chinese medicine and suggest a novel therapeutic strategy for the treatment of inflammation-related diseases.

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 observe the therapeutic effect and mechanism of Leonurine on hepatitis B rats.Methods Sixty rats were randomly divided into six groups,i.e.,the normal group,the model group,the Leonurine low-,medium-and high-dose groups,and the Leonurine high-dose+lysophosphatidic acid(LPA)group.Hepatitis B model was constructed for rats in all groups except for the normal group.After successful modeling,each group was given corresponding invention.At the end of administration,the levels of serum hepatitis B e antigen(HBeAg),hepatitis B surface antigen(HBsAg),and inflammatory factors such as interleukin(IL)-10,IL-6 and tumor necrosis factor α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA),and levels of serum alanine aminotransferase(ALT)and aspartate transaminase(AST)were detected by automatic analyzer.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect HBV DNA level in liver tissues,hematoxylin-eosin(HE)staining was used to observe the pathological changes in liver tissues,immunohistochemistry was used to detect the expression of hepatitis B core antigen(HBcAg)in liver tissues,and Western Blot was used to detect the expression of Ras homolog gene family member A(RhoA),Rho-associated coiled-coil containing kinases(ROCK)1 and ROCK2.Results Compared with the normal group,necrosis in the center of hepatic lobules,edema and degeneration of hepatocytes in rats was showed in the model group,and the levels of HBsAg,HBeAg and HBV DNA,HBcAg-positive cell counts,the levels of ALT and AST,the contents of IL-6,TNF-α and IL-10,and the expression levels of RhoA,ROCK1,ROCK2 were significantly increased(all P＜0.05).Compared with the model group,liver damage degree was decreased and cellular degeneration was reduced in rats in the Leonurine low-,medium-and high-dose groups,the levels of HBsAg,HBeAg and HBV DNA,HBcAg-positive cell counts,the levels of ALT and AST,the contents of IL-6 and TNF-α,and the expression levels of RhoA,ROCK1 and ROCK2 were significantly decreased,and the IL-10 level were significantly increased,the differences being statistically significant(P＜0.05).Compared with the Leonurine high-dose group,the degree of liver damage was increased in the Leonurine high-dose+LPA group,the levels of HBsAg,HBeAg and HBV DNA,HBcAg-positive cell counts,the levels ALT and AST,contents of IL-6 and TNF-α,and the expression levels of RhoA,ROCK1 and ROCK2 were significantly increased,and IL-10 level was significantly decreased,the differences being statistically significant(P＜0.05).Conclusion Leonurine can relieve liver injury,improve liver function and reduce inflammatory reaction in hepatitis B rats,and its mechanism is related to the inhibition of RhoA/ROCK pathway.

Objective: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA). Materials and Methods: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates.In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates. Results: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0–40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%–86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%–19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%–11.4%), 26.8% (95% CI: 2.7%– 44.9%), and 51.2% (95% CI: 0%–79.1%), respectively. No significant differences were observed in the disease progression (P = 0.829) or complete tumor disappearance (P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355). Conclusion Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences.