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.

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 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 investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer.Methods:This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded.Results:All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient.Conclusions:The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

Objective:To explore the methods and clinical effects of reconstructing facial and cervical scars with expanded flaps based on the "MLT" principle.Methods:The study was a retrospective observational study. From January 2019 to May 2022, 74 patients with facial and cervical scars after burn or trauma injuries who met the inclusion criteria were admitted to Xiangya Hospital of Central South University, including 38 males and 36 females, aged from 5 to 58 years, including 24 patients with simple facial involvement, 24 patients with simple cervical involvement, and 26 patients with both facial and cervical involvement, with scar area ranging from 12 to 145 cm2. By following the "MLT" principle (color and texture similar to the face; flap area large enough to reconstruct the entire defect; skin tissue thin enough to transmit the expression, so as to facilitate the shape of the face and five features); in the stage Ⅰ surgery, the skin and soft tissue expanders (hereinafter referred to as the expanders) were implanted, and in the stage Ⅱ surgery, the expander removal+scar resection+flap transplantation to repair the secondary wound was performed, and the wound in the donor area of flap was directly sutured. After operation, silicone gel preparation and laser therapy were used to prevent scar hyperplasia. The expansion ratio and time period of expanders, the occurrence of complications of skin and soft tissue expansion surgery, the type of flap used, and the survival of flap after the stage Ⅱ surgery were observed and recorded. The long-term effect of facial and cervical reconstruction and the recovery of donor area and recipient area of flap were evaluated during the postoperative follow-up after surgery.Results:The expansion ratio of 135 expanders ranged from 1.36 to 3.00 times, and the expansion time period ranged from 6 to 14 months. During skin and soft tissue expansion surgery, 8 patients had poor healing of incisions after expander placement, 7 patients had expander rupture, 5 patients had infection in incisions after expander placement, 3 patients had expander exposure, 2 patients had difficult filling the injection pot, and 1 patient had water leakage from the injection pot. Dorsal shoulder expanded flaps with double blood supply of transverse cervical artery and circumflex scapular artery were used in 8 patients, the expanded flaps of anterior transverse carotid artery perforator were used in 11 patients, the expanded flaps of internal thoracic artery perforator were used in 12 patients, tandem expanded flaps of upper chest and neck were used in 16 patients, dorsal thoracic artery perforator expanded flaps were used in 5 patients, and adjacent rotary propulsive expanded flaps were used in 22 patients. After the stage Ⅱ surgery, the flaps of 71 patients were completely survived. One patient had blood circulation disorder in the flap, and the flap survived after hyperbaric oxygen treatment. Necrosis occurred at the end of the flaps in 2 patients, which healed after dressing change. After the surgery, 42 patients were followed up for 3 to 24 months. The color, texture, and thickness of flaps were good and similar to the surrounding normal skin tissue in the recipient area, the appearance and function of the face and neck were significantly improved, and the wound location in the donor and recipient areas of flaps was concealed with slight scar formation.Conclusions:In the reconstruction of facial and neck scars, by following the "MLT" principle, the expanded flap was carefully designed before surgery, the local aesthetic features within the subunit are reconstructed during the stage Ⅱ surgery, and standard anti-scar treatment measures are actively adopted after surgery. After reconstruction, the color, texture, and thickness of flaps were close to the normal skin in face and neck, and the appearance and function of face and neck are significantly improved, with less linear scars left. It is beneficial to improve the therapeutic effect.

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.