Objective To explore the technical process and clinical application of laparoscopic combined upper midline incision minimally invasive liver transplantation. Methods A retrospective analysis was conducted on 30 cases of laparoscopic combined upper midline incision minimally invasive liver transplantation. The cases were divided into cirrhosis group (15 cases) and liver failure group (15 cases) based on the primary disease. The surgical and postoperative conditions of the two groups were compared. Results All patients successfully underwent laparoscopic "clockwise" liver resection, with no cases of passive conversion to open surgery or intolerance to pneumoperitoneum. In 6 cases, the right lobe was relatively large, and the right hepatic ligaments could not be completely mobilized. One case required an additional reverse "L" incision during open surgery. All patients successfully completed the liver transplantation, with no major intraoperative bleeding, cardiovascular events, or other occurrences in the 30 patients. The model for end-stage liver disease (MELD) score in the cirrhosis group was lower than that in the liver failure group (P<0.001). There were no statistically significant differences between the two groups in terms of age, surgical time, blood loss, anhepatic phase, or cold ischemia time (all P>0.05). During the perioperative period, there was 1 case of hepatic artery embolism, 1 case of portal vein anastomotic stenosis, no complications of hepatic vein and inferior vena cava, and 3 cases of biliary anastomotic stenosis, all of which occurred in the liver failure group. Conclusions In strictly selected cases, the minimally invasive liver transplantation technique combining laparoscopic hepatectomy with upper midline incision for graft implantation has the advantages of smaller incisions, less bleeding, relatively easier operation, and faster postoperative recovery, which is worthy of clinical promotion and application.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Radical gastrectomy is the core of comprehensive treatment for patients with locally advanced gastric cancer,while reasonable and standardized lymphadenectomy is the key to radical gastrectomy.With the continuous development of treatment methods and therapeutic drugs for advanced gastric cancer, it is worth exploring whether the scope of lymphadenectomy needs to be changed. Neoadjuvant immunotherapy has brought a new breakthrough for locally advanced gastric cancer, increased pathological complete response rate, reduced clinical stage of tumors, and increased radical surgical resection rate, but it has not brought long-term benefits to patients. Lymph nodes play an important role in human anti-tumor immune response, and some basic studies suggest that preserving some normal lymph nodes may be more helpful to enhance the efficacy of immunotherapy. Thus, in the era of immunotherapy, the extent of lymph node dissection for locally advanced gastric cancer needs to balance continuous drug benefits, patient quality of life, and survival benefits, awaiting further high-quality clinical research for determination. Questions such as how to differentiate between normal and metastatic lymph nodes, how to rationally preserve normal lymph nodes, and whether preserving partial lymph node function can lead to greater benefits for patients from immunotherapy warrant further exploration.

Radical gastrectomy is the core of comprehensive treatment for patients with locally advanced gastric cancer,while reasonable and standardized lymphadenectomy is the key to radical gastrectomy.With the continuous development of treatment methods and therapeutic drugs for advanced gastric cancer, it is worth exploring whether the scope of lymphadenectomy needs to be changed. Neoadjuvant immunotherapy has brought a new breakthrough for locally advanced gastric cancer, increased pathological complete response rate, reduced clinical stage of tumors, and increased radical surgical resection rate, but it has not brought long-term benefits to patients. Lymph nodes play an important role in human anti-tumor immune response, and some basic studies suggest that preserving some normal lymph nodes may be more helpful to enhance the efficacy of immunotherapy. Thus, in the era of immunotherapy, the extent of lymph node dissection for locally advanced gastric cancer needs to balance continuous drug benefits, patient quality of life, and survival benefits, awaiting further high-quality clinical research for determination. Questions such as how to differentiate between normal and metastatic lymph nodes, how to rationally preserve normal lymph nodes, and whether preserving partial lymph node function can lead to greater benefits for patients from immunotherapy warrant further exploration.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood in vitro. Methods GO nanoparticles prepared using a probe sonicator were supended in deionized H2O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG). Results GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H2O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4+T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO. Conclusion GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.

Objective To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood in vitro. Methods GO nanoparticles prepared using a probe sonicator were supended in deionized H2O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG). Results GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H2O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4+T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO. Conclusion GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.

β2-adrenergic receptor （β2-AR） agonists are widely used as first-line drugs in the treatment of bronchial asthma （hereinafter referred to as “asthma”）， but long-term use can lead to β2-AR desensitization and reduce its clinical efficacy， resulting in poor symptom control of some asthma patients. The mechanism of β2-AR desensitization induced by β2-AR agonists mainly includes slow hyposensitization （related to the decrease of β2-AR density in airway mucosa） and rapid hyposensitization （related to the mechanism of stimulatory G protein decoupling）. Cyclic adenosine monophosphate（cAMP）-protein kinase A and cAMP- exchange protein activated by cAMP signaling pathways are closely related to β2-AR desensitization. Glucocorticoids， peroxisome proliferator-activated receptor-gamma agonists， ASM-024， Chinese medicine monotherapies and formulations， when combined with β2-AR agonists， can improve the sensitivity of β2-AR， so as to better control asthma symptoms.

Objective:To predict the molecular mechanism of Biminkang Granules in the treatment of allergic rhinitis using network pharmacological methods combined with animal experiments.Methods:Active component targets and allergic rhinitis targets were screened from TCMSP, OMIM, GeneCards, TTD, DrugBank and PharmGKB databases; R language software was used to map the intersection of drug and disease targets; Cytoscape software and String platform were used to construct intersection target PPI network and conduct network topology analysis; DAVID platform was used to perform GO enrichment and KEGG pathway analysis, and perform molecular docking verification on the main active components and key targets. 32 rats were divided into a blank group of 8 and a model group of 24 using a random number table method. Model rats were induced by ovalbumin to establish an allergic rhinitis model. 24 SD rats that were successfully modeled and were randomly divided into model group, Western medicine group, and Biminkang Granules group using a random number table method, with 8 rats in each group. The Western medicine group was gavaged with 1 mg/kg of loratadine solution, the Biminkang Granules group was gavaged with 4.1 g/kg of Biminkang Granules solution, and the blank group and model group rats were gavaged with the same volume of physiological saline once a day for 2 consecutive weeks. The symptoms of rhinitis in each group of rats for 30 minutes were observed and recorded, and the pathological changes of the rat nasal mucosa were observed using HE staining. ELISA method was used to detect the levels of IL-17 and IL-6 in rat serum, and Western blot method was used to determine the expressions of TNF and STAT3 proteins in rat tissues.Results:A total of 41 target proteins of BiMinKang Dranule in the treatment of allergic rhinitis were predicted, and TNF, STAT3 and other core target proteins were obtained by PPI network topology analysis. The biological process of GO involved drug response, inflammatory response, cytokine response, etc.KEGG enrichment is involved in Th17 cell differentiation, lipid and atherosclerosis, IL-17, toll-like receptor and other pathways. Molecular docking results indicated that the main active components had good binding activity to key target proteins.Animal experiments showed that BiMinKang Dranule could improve the inflammatory symptoms of allergic rhinitis rats, down-regulate the expression of IL-17 and IL-6 in blood, and inhibit the expression of TNF and STAT3 proteins.Conclusion:Biminkang Granules can treat allergic rhinitis through multiple active components, multiple target proteins and multiple pathways, and the mechanism may be related to the regulation of Th17 cell differentiation pathway related proteins.