Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Objective:To explore the clinical application effects of tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs.Methods:The study was a retrospective observational study. From March 2019 to March 2024, 7 male patients with destructive wounds in the lower limbs who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University, aged 35 to 57 years. After clinical treatment, the damaged limbs were still difficult to preserve. Five patients with destructive wounds in the lower limbs were repaired with pedicled tissue flaps prepared from the discarded limbs after amputation, with wound areas of 15 cm×10 cm to 25 cm×15 cm and tissue flap incision areas of 15 cm×10 cm to 20 cm×15 cm. Two patients with destructive wounds in the lower limbs were repaired with free tissue flaps prepared from the discarded limbs after amputation, with wound areas of 22 cm×18 cm and 25 cm×15 cm and tissue flap incision areas of 23 cm×20 cm and 25 cm×18 cm. The survival of the tissue flap, the healing and appearance of wounds in the recipient site were followed up. At the last follow-up, the recovery status of the recipient site was evaluated according to the comprehensive flap evaluation scale, and the status of corrective prosthesis fitting was recorded.Results:During the follow-up of 6 to 24 months, all the tissue flaps successfully survived, with good healing and appearance of wounds in the recipient site. At the last follow-up, the scores of the recovery status of the recipient site ranged from 36 to 39 (with an average of 37.2). All amputated limbs were able to accommodate corrective prostheses with no distal ulceration.Conclusions:Utilizing tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs to repair wounds effectively uses the discarded tissue and avoid creating new donor sites, which is a method to be considered for repairing multiple destructive wounds.

Objective:To systematically evaluate the incidence and risk factors of acute kidney injury (AKI) induced by vancomycin in pediatric patients.Methods:Databases of PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, Chinese Biomedical Database (CBM) were searched and articles about the risk factors of AKI induced by vancomycin in pediatric patients from inception to June 2024 were collected. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS) for the included studies. Meta-analysis of the data for relevant exposure factors extracted from the included literature was conducted using Rev Man 5.4. The strength of association between the exposure factors and AKI was expressed using the odds ratio ( OR) and its 95% confidence interval ( CI). Results:A total of 13 studies were entered, involving 11 073 patients. Of them, 1 388 patients were in AKI group and 9 685 patients in non-AKI group. The incidence of AKI was 12.53%, ranging from 4.62% to 27.07%. The quality evaluation results showed that the 13 documents were all of high-quality (NOS score ≥7 points). Meta-analysis showed that admission to intensive care unit (ICU) ( OR=2.39, 95% CI: 1.59-3.59, P<0.001), vancomycin using time ≥7 d ( OR=2.19, 95% CI: 1.44-3.34 P=0.003), vancomycin steady-state trough concentration ≥15 mg/L ( OR=2.98, 95% CI: 2.22-4.01, P<0.001), combined with nephrotoxic drugs ≥2 kinds ( OR=2.92, 95% CI=1.84-4.64, P<0.001), combined with piperacillin sodium and tazobactam sodium ( OR=2.71, 95% CI: 1.72- 4.27, P<0.001), combined with carbapenem ( OR=2.36, 95% CI: 1.36-4.10, P=0.002), combined with aminoglycosides ( OR=1.78, 95% CI: 1.35-2.35, P<0.001), combined with loop diuretics ( OR=3.16, 95% CI: 2.36- 4.23, P<0.001), combined with amphotericin B ( OR=2.26, 95% CI: 1.35-3.79, P=0.002), combined with contrast medium ( OR=2.34, 95% CI: 1.04-5.25, P=0.040), and combined with aciclovir ( OR=1.74, 95% CI: 1.04-2.84, P=0.030) were all risk factors of AKI induced by vancomycin in pediatric patients. Conclusions:The incidence of vancomycin-related AKI in pediatric patients was 12.53%. Admission to ICU, vancomycin trough concentration ≥15 mg/L, medication time ≥7 d, and concomitant use of ≥2 nephrotoxic drugs and etc.were risk factors of vancomycin-related AKI.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Objective:To systematically evaluate the incidence and risk factors of acute kidney injury (AKI) induced by vancomycin in pediatric patients.Methods:Databases of PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, Chinese Biomedical Database (CBM) were searched and articles about the risk factors of AKI induced by vancomycin in pediatric patients from inception to June 2024 were collected. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS) for the included studies. Meta-analysis of the data for relevant exposure factors extracted from the included literature was conducted using Rev Man 5.4. The strength of association between the exposure factors and AKI was expressed using the odds ratio ( OR) and its 95% confidence interval ( CI). Results:A total of 13 studies were entered, involving 11 073 patients. Of them, 1 388 patients were in AKI group and 9 685 patients in non-AKI group. The incidence of AKI was 12.53%, ranging from 4.62% to 27.07%. The quality evaluation results showed that the 13 documents were all of high-quality (NOS score ≥7 points). Meta-analysis showed that admission to intensive care unit (ICU) ( OR=2.39, 95% CI: 1.59-3.59, P<0.001), vancomycin using time ≥7 d ( OR=2.19, 95% CI: 1.44-3.34 P=0.003), vancomycin steady-state trough concentration ≥15 mg/L ( OR=2.98, 95% CI: 2.22-4.01, P<0.001), combined with nephrotoxic drugs ≥2 kinds ( OR=2.92, 95% CI=1.84-4.64, P<0.001), combined with piperacillin sodium and tazobactam sodium ( OR=2.71, 95% CI: 1.72- 4.27, P<0.001), combined with carbapenem ( OR=2.36, 95% CI: 1.36-4.10, P=0.002), combined with aminoglycosides ( OR=1.78, 95% CI: 1.35-2.35, P<0.001), combined with loop diuretics ( OR=3.16, 95% CI: 2.36- 4.23, P<0.001), combined with amphotericin B ( OR=2.26, 95% CI: 1.35-3.79, P=0.002), combined with contrast medium ( OR=2.34, 95% CI: 1.04-5.25, P=0.040), and combined with aciclovir ( OR=1.74, 95% CI: 1.04-2.84, P=0.030) were all risk factors of AKI induced by vancomycin in pediatric patients. Conclusions:The incidence of vancomycin-related AKI in pediatric patients was 12.53%. Admission to ICU, vancomycin trough concentration ≥15 mg/L, medication time ≥7 d, and concomitant use of ≥2 nephrotoxic drugs and etc.were risk factors of vancomycin-related AKI.

Objective:To explore the clinical application effects of tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs.Methods:The study was a retrospective observational study. From March 2019 to March 2024, 7 male patients with destructive wounds in the lower limbs who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University, aged 35 to 57 years. After clinical treatment, the damaged limbs were still difficult to preserve. Five patients with destructive wounds in the lower limbs were repaired with pedicled tissue flaps prepared from the discarded limbs after amputation, with wound areas of 15 cm×10 cm to 25 cm×15 cm and tissue flap incision areas of 15 cm×10 cm to 20 cm×15 cm. Two patients with destructive wounds in the lower limbs were repaired with free tissue flaps prepared from the discarded limbs after amputation, with wound areas of 22 cm×18 cm and 25 cm×15 cm and tissue flap incision areas of 23 cm×20 cm and 25 cm×18 cm. The survival of the tissue flap, the healing and appearance of wounds in the recipient site were followed up. At the last follow-up, the recovery status of the recipient site was evaluated according to the comprehensive flap evaluation scale, and the status of corrective prosthesis fitting was recorded.Results:During the follow-up of 6 to 24 months, all the tissue flaps successfully survived, with good healing and appearance of wounds in the recipient site. At the last follow-up, the scores of the recovery status of the recipient site ranged from 36 to 39 (with an average of 37.2). All amputated limbs were able to accommodate corrective prostheses with no distal ulceration.Conclusions:Utilizing tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs to repair wounds effectively uses the discarded tissue and avoid creating new donor sites, which is a method to be considered for repairing multiple destructive wounds.

OBJECTIVE To create a highly effective algorithm for automatically generating easily confused drug catalogs （ECDC）， as well as to develop a management system for ECDC based on this algorithm， in order to improve the management efficiency of ECDC. METHODS This study， based on Levenshtein distance algorithm， delved deeply into the automatic identification mechanism of easily confused drugs and the screening method for determining similarity thresholds， ultimately leading to the development of an algorithm for automatically generating ECDC. Besides a management system was designed and developed， using SQL Server 2008 R2 Express as the data storage platform and Visual Basic.NET as the programming language. RESULTS The similarity threshold δ played a crucial role in the algorithm for automatically generating ECDC. As the value of δ gradually increased， the total count of easily confused drugs decreased gradually， while the count of drug groups exhibited a pattern of initially increasing and then decreasing. Practically， ECDC could be created using either the generic or varietal names of drugs， with corresponding similarity thresholds of 0.75 and 0.83. Furthermore， ECDC management system had significantly reduced the time required to establish a catalog from about one week to less than one hour， resulting in a substantial enhancement in work efficiency. CONCLUSIONS The algorithm used to automatically generate ECDC is highly efficient and rapid， offering robust technical assistance for the management of easily confused drugs. Implementing the ECDC system can greatly reduce the time cost related to building and maintaining the catalogs， thus significantly improving the efficiency of managing ECDC.

Objective To study the role and mechanisms of equilibrative nucleotide transporter 1(ENT1)on Alzheimer's disease(AD)by constructing ENT1 overexpression and knockdown plasmids.Methods Molecular cloning was used to construct the ENT1 overexpression(pAAV-ENT1-mCherry)and knockdown(pAAV-ENT1shRNA-ZsGreen)plasmids.The overexpression plasmids and the knockdown plasmids were transfected into N2A cells(mouse Neuro A2 cells)and N2A-APP cells(N2A cells stably expressing human APP695).The expression of ENT1 and inflammatory factors at mRNA and protein levels were detected by real-time qPCR and Western blotting,respectively,and the change in cell viability were measured with CCK-8 assay.Results Sequencing and real-time qPCR indicated that ENT1 overexpression and knockdown plasmids were successfully constructed.CCK-8 assay showed that ENT1 overexpression significantly reduced the cell survival rate within 24 h(P＜0.05),while its knockdown increased the cell survival rate(P＜0.01).Real-time qPCR displayed that overexpression of ENT1 enhanced the expression levels of inflammatory factors,such as IL-1β,TNF-α,C1q-a and C1q-b in N2A cells(P＜0.05),while ENT1 knockdown reversed the above changes in inflammatory factors in N2A-APP cells(P＜0.05).Conclusion Knockdown of ENT1 attenuates pathological changes in AD by reducing the inflammatory response.ENT1 may be a potential target in the pathological mechanism of AD.

Skin wounds are global public problems,especially in terms of the difficult healing of chronic wounds,which may seriously affect patients'lives.Most skin-wound animal models are currently established by physical method,and different animal models have different biological characteristics.This review therefore classifies mouse,rat,and other animal models of skin wounds according to the literature,summarizes and analyzes the construction of skin-wound animal models based on physical method and evaluation indicators,and considers the advantages and disadvantages of different animal models,to provide a basis for the rational construction of skin-wound animal models and drug research and development.