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.

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.

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.

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.

Objective:To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis.Methods:A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ2 test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results:There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP ( OR=1.32, 95% CI: 1.12-1.56, P=0.001). Patients combined with EGV ( OR=3.09, 95% CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism ( P<0.001). Patients with PBC ( OR=0.64, 95% CI: 0.50-0.82, P<0.001) and PSC ( OR=0.23, 95% CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients ( P<0.001), and the lower proportion of hypersplenism in combined PSC patients ( P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures ( P<0.05), but a lower rate of liver biopsy ( P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without ( P=0.004). Conclusion:TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.

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.

BACKGROUND: Insufficient angiogenesis and the lack of skin appendages are critical challenges in cutaneous wound healing. Stem cell-fabricated cell sheets have become a promising strategy, but cell sheets constructed by a single cell type are inadequate to provide a comprehensive proregenerative microenvironment for wound tissue. METHODS: Based on the communication between cells, in this study, bone marrow mesenchymal stem cells (BMSCs) and hair follicle stem cells (HFSCs) were cocultured to fabricate a composite cell sheet (H/M–CS) for the treatment of fullthickness skin wounds in mice. RESULTS: Experiments confirmed that there is cell–cell communication between BMSCs and HFSCs, which enhances the cell proliferation and migration abilities of both cell types. Cell–cell talk also upregulates the gene expression of proangiogenic-related cytokines in BMSCs and pro-hair follicle-related cytokines in HFSCs, as well as causing changes in the properties of secreted extracellular matrix components. CONCLUSIONS Therefore, the composite cell sheet is more conducive for cutaneous wound healing and promoting the regeneration of blood vessels and hair follicles.

Objective:To explore the repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness.Methods:A retrospective observational study was conducted. From January 2020 to May 2022, 5 patients admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University and 4 patients admitted to the Department of Burns and Plastic Surgery of Chenzhou First People's Hospital with complex facial defect wounds involving paranasal sinuses met the inclusion criteria, including 6 males and 3 females, aged 35-69 years, including 4 patients with titanium mesh exposure combined with paranasal sinuses injury and 5 patients with tumor involving paranasal sinuses. After an adequate assessment of the damage by a multiple discipline team, titanium mesh removal, paranasal sinus debridement, and paranasal sinus mucosa removal were performed in patients with exposed titanium mesh, and radical tumor resection was performed in patients with tumors, with postoperative skin and soft tissue defects areas of 5.0 cm×2.5 cm to 18.0 cm×7.0 cm, anterior paranasal sinus wall defects/absence areas of 3 cm×2 cm to 6 cm×4 cm, and sinus cavity depths of 1 to 4 cm. Depending on the perforator course of the descending branch of the lateral circumflex femoral artery, the anterolateral femoral chimeric flap or anterolateral femoral myocutaneous flap (with flap area of 9 cm×4 cm to 19 cm×8 cm, muscle size of 5 cm×3 cm×3 cm to 11 cm×6 cm×3 cm) was transplanted to repair the defect, and the donor site wound was sutured directly. The type of tissue flap transplanted, the blood vessel of the recipient area, and the vascular anastomosis way during the operation, the recovery of the donor and recipient areas and the occurrence of complications after operation were observed. The appearance and blood supply of the recipient area and the recurrence of ulcers and tumors were followed up.Results:The anterolateral femoral myocutaneous flap transplantation was performed in 6 patients, and the anterolateral femoral chimeric flap transplantation was performed in 3 patients. The blood vessels in recipient areas were facial arteries and veins in 3 cases and superficial temporal arteries and veins in 6 cases. The superficial temporal arteries and veins were bridged with blood vessels in tissue flaps by flow-through way in 2 patients, and end-to-end anastomosis of blood vessels in donor and recipient areas was performed in 7 patients. After operation, all the tissue flaps survived, and the facial defect wounds were well repaired without cerebrospinal fluid leakage or paranasal sinus secretion leakage, no intracranial infection occurred, and the wounds in donor areas were healed well. Follow-up of 6-35 months after operation showed that all the patients had good blood supply in the recipient area, and the shape was acceptable; 4 patients with exposed titanium mesh had no recurrence of ulceration, and 5 patients with tumor had no local tumor recurrence or metastasis.Conclusions:Based on an adequate assessment of the extent of paranasal sinuses involved in the facial wound and the nature of the defect, good clinical effects can be achieved by using the anterolateral femoral muscle flap or the anterolateral femoral chimeric flap transplantation to repair complex facial defect wounds with open paranasal sinuses.

Imipenem-cilastatin is a broad-spectrum carbapenem antibiotic drug that has been widely used in clinical practice ， but there is a lack of guidelines and expert consensus on the development of individualized regimens for special status populations [e.g. continuous renal replacement therapy （CRRT）patients，extracorporeal membrane oxygenation （ECMO）patients， critically ill burn patients ，neonates and children]. In this paper ，by searching population pharmacokinetics research of imipenem- cilastatin in special status populations ，it is recommended that imipenem-cilastatin is given 1 to 3 g/d for CRRT patients ；500 mg to 1 g，q6 h for burn patients ；750 mg to 1 g，q6 h for ECMO patients ；20 mg/kg or 25 mg/kg，q8 h for neonates ；and 25 mg/kg，q6 h for children.