Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Acute skin failure (ASF) is an inevitable damage to the skin and subcutaneous tissue caused by hemodynamic instability and/or low perfusion. At present, there are some understandings and reports about adult ASF at home and abroad, but there are few reports about children's ASF. This article reviewed the definition, pathophysiological changes, risk factors, clinical manifestations, and management of children's ASF, and put forward suggestions in order to provide ideas for clinical diagnosis and treatment of children's ASF, and promote the further study of children's ASF.

During the process of dairy farming,various factors such as physical injury and bacterial infection act upon body tissues or organs,leading to the disruption of skin or mucous tissue integ-rity and subsequent tissue injury and trauma.The healing of these injuries is a complex process that necessitates the coordinated efforts of different cells and involvement of diverse cytokines.A-mong them,the interaction between macrophages and myofibroblasts is indispensable for efficient tissue repair.Nod-like receptor protein 3(NLRP3),a pattern recognition receptor in the innate im-mune system,may play a regulatory role in modulating this intricate process.In this study,cow myofibroblasts and M1 type bone marrow-derived macrophages were cultured in vitro,followed by collection of cell culture supernatant for co-culture analysis.Both cytokine secretion levels in M1 type bone marrow-derived macrophages as well as expression patterns levels of myofibroblast growth factor protein and mRNA were detected.The regulatory mechanism underlying NLRP3 in-volvement in mediating interactions between these two cell types was investigated using NLRP3 inhibitor MCC950.The results showed that an effective method for culturing cow muscle fibroblasts in vitro was successfully established and myofibroblast conditioned medium(MFbCM)could regulate M1 macrophage secretion profiles.Moreover,M1 macrophage conditioned medium(M1?CM)was found to influence myofibroblast growth factor expression levels.Our findings sug-gest that NLRP3 plays a significant regulatory role during crosstalk between myofibroblasts and M1-type pro-inflammatory macrophages.

Objective:To compare laparoscopic versus laparotomy in the treatment of colorectal cancer liver metastases (CRLM).Methods:The clinical data of 78 consecutive patients with CRLM operated at Department of Hepatic Surgery, Fudan University Shanghai Cancer Center from April 2015 to August 2016 were analyzed retrospectively. There were 52 males and 26 females. The average was (56.8±9.9) years. The patients were divided into the laparoscopic group ( n=26) and laparotomy groups ( n=52). The operation time, intraoperative blood loss, extent of hepatectomy, postoperative liver function and complications were compared between the two groups. The follow-up data was used to compare the long-term survival outcomes. Results:There were no significant differences between the two groups in operation time, intraoperative bleeding volume and extent of hepatectomy ( P>0.05). The percentage of patients who underwent preoperative neoadjuvant chemotherapy in the laparotomy group was significant higher, and the diameter of liver metastasis was significantly larger than that in the laparoscopic group ( P<0.05). On day 1 after operation, the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the laparoscopic group were (502.2±115.3) U/L and (570.4±132.4) U/L, respectively, which were significantly better than those in the laparotomy group (683.9±150.1) U/L and (739.5±230.2) U/L, respectively ( P<0.05). On day 3 after operation, the ALT and AST levels in the laparoscopic group were (263.3±83.3) U/L, (271.4±87.3) U/L, which were still significantly superior than those in the laparotomy group (410.8±128.4) U/L and (489.1±125.6) U/L ( P<0.05). Complications occurred in 4 patients (15.4%) in the laparoscopic group and 19 patients (36.5%) in the laparotomy group, the difference was significant ( P<0.05). The recurrence and extrahepatic metastasis rates of the laparoscopic group were better than those of the laparotomy group, and the survival outcomes were better than the laparotomy group. Conclusion:Laparoscopic surgery was better than laparotomy surgery in the treatment of CRLM. Laparoscopic surgery should be further promoted.

Objective:To investigate the value of total laparoscopic simultaneous resection for left-sided colorectal cancer (CRC) and synchronous liver metastases (SLM).Methods:A retrospective analysis of the clinical data of patients with left-sided CRC and SLM who underwent simultaneous resection in the Shanghai Cancer Center, Fudan University from March 2014 to December 2017. The patients were divided into laparoscopy group, open surgery group and hybrid surgery group. The intraoperative information, postoperative short-term outcome and long-term survival were analyzed among the three groups.Results:A total of 96 patients were enrolled. The total laparoscopic group enrolled 29 patients, including 21 males and 8 females, aged (57.8±1.6) years old; the open surgery group enrolled 28 patients, including 18 males and 10 females, aged (57.3±2.0) years old; 39 cases were included in the hybrid surgery group, including 27 males and 12 females, aged (55.3±1.8) years old. The distribution ratio of the two lobes of liver metastases in the open surgery group was higher than that in the total laparoscopic group and hybrid surgery group (all P<0.05), and there was no significant difference in the other clinical baseline characteristics between the three groups (all P>0.05). In laparoscopy group, open surgery group and hybrid surgery group, the mean operative time was (241.5±12.9) min, (209.3±10.7) min and (234.9±12.4) min, respectively. The median intraoperative blood loss was 200.0 ml, 300.0 ml and 200.0 ml, respectively. The median postoperative hospital stay was 8.0 days, 9.0 days and 9.0 days, respectively. There were no statistical differences in these indicators (all P>0.05). The patients in the open surgery group had a longer initial defecation time than those in the other two groups ( P<0.05). The incidence of postoperative complications was 31.0% (9/29), 39.3% (11/28) and 35.9% (14/39), respectively, with no difference among the three groups ( P>0.05). In laparoscopy group, open surgery group and hybrid surgery group, 1-year overall survival were 93.0%, 85.0% and 94.0%; 3-year overall survival were 72.0%, 81.0% and 74.0%, respectively ( P>0.05). One-year disease free survival were 70.0%, 52.0% and 55.0%; 3-year disease free survival were 36.0%, 30.0% and 39.0%, respectively ( P>0.05). Conclusion:Laparoscopic simultaneous resection for left-sided CRC and SLM shows slight advantages in the safety and short-term outcome, and does not affect the long-term survival.

Pancreatic duct stone is a sequel of chronic pancreatitis and may be found in the main ducts,side branches or parenchyma.These stones obstruct the pancreatic ducts and produce ductal hypertension,which leads to pain,the cardinal feature of CP.Surgical operation has been the preferred treatment of pancreatic duct stones in many domestic and external pancreatic medical centers.Lithotomy by longitudinal pancreatic duct incision and Roux-en-Y anastomosis of pancreatic duct to jejunum is the main and effective surgical procedure,while micro-surgery was also rational for the treatment of pancreatic duct stones.However,further studies with a larger sample size and longer follow-up duration are needed to improve the surgical technique and verify our initial results.

Background and purpose: With the application of laparoscopy in the liver surgery increasingly widely used, the safety and feasibility of laparoscopic liver resection is gaining recognition gradually. This study aimed to explore the laparoscopic liver resection for the tumor and the feasibility of open liver tumor resection and clinical curative effect. Methods: We retrospectively analysed the clinical data from 37 cases of laparoscopic hepatectomy and 74 patients with open liver resection from Mar. 2015 to Mar. 2016. Measurement data by covariance analysis were obtained, and comparison between groups were made using independent sample with Wilcoxon rank test and statistical value of Z. We collected data including operation time, intra-operative blood loss, post-operative recovery time of gastrointestinal tract, surgical drainage tube after extubation time, length of hospital stay, postoperative complications, hospitalization expenses and other clinical data. Laparoscopic group had 20 males and 17 female aged 18 to 76 (median age 55). Open group had 42 males and 32 females aged 26 to 74 (median age 54). The hepatectomy included ultrasonic knife + unipolar electric coagulation, combined with laparoscopic incision suture. Surgery procedures included 13 cases of local excision in laparoscopic group and 24 cases of liver segment or lobe anatomical resection. Open group had 33 cases of local excision and 41 cases of liver segment or lobe anatomical resection. Results: The average duration of laparoscopic hepatectomy was 149 min (40-204 min). The average duration of open hepatectomy was 142 min (45-190 min). The average intra-operative blood loss was 220 mL (30-570 mL) in laparoscopic group and 360 mL (90-970 mL) in open group. The average length of hospital stay was 4.9 d (3-6 d) in laparoscopic group and 6.8 d (5-9 d) in open group. Gastrointestinal average recovery time was 1.1 days in laparoscopic group and 2.3 days in open group. The average hospitalization expenses were 38760 yuan in laparoscopic group and 39145 yuan in open group. Conclusion:Laparoscopic hepatectomy is a safe, effective and minimally invasive surgery, can be safely used in local, liver segment and half liver resection, worthy of promotion.

Background and purpose:It was reported that many microRNAs (miRNAs) have close relation with carcinomas. miR-31 (microRNA-31) shows abnormal change in numerous cancers. China is one of the most high-risk areas of esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the expression of miR-31 in ESCC, and analyze the relationship of its expression with clinicopathological features and prognosis. Methods:The expression of miR-31 in KYSE410, EC1 and EC9706 cell lines, as well as 81 cases of ESCC tissues and adjacent normal esophageal tissues were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). The result was combined with clinical and follow-up data and statistical analysis was conducted. Results: MiR-31 was up-expression in 3 cell lines and 75.31% of the ESCC tissues. miR-31 up-expression was positively related to severer lymph node metastasis (P=0.043), deeper invasion of tumors (P=0.002) and advanced pathological stage (P=0.027). There was no relationship of miR-31 with other clinicopathological features (P>0.05). Furthermore, high expression of miR-31 was associated with poor progression-free survival (PFS) in 81 ESCC patients by Kaplan-Meier analysis (P=0.014) and by multivariate Cox analysis (P=0.021). Conclusion:Our results identiifed miR-31 may be a new diagnostic criteria and prognostic biomarker for ESCC.