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The aim of this study is to delineate the expression patterns of prolyl cis-trans isomerase NIMA-interacting protein 1 (Pin1), Glial cell-derived neurotrophic factor (GDNF), and Angiotensin II (ANG II) during the process of wound repair, and to ascertain the effects of Pin1, GDNF, and ANG II on the healing of wounds in a rat model. A total of 18 rats were allocated into three groups—sham (control), DMSO (vehicle control), and Pin1 inhibitor (treatment with juglone)—with six animals in each group. An animal model of wound healing was established, followed by the intraperitoneal administration of juglone. Tissue samples from the wounds were subsequently collected for histopathological evaluation. Expression levels of Pin1, GDNF, and Ang II were quantified. In addition, an in vitro model of wound healing was created using human umbilical vein endothelial cells (HUVEC), to assess cell proliferation, migration, and tube formation under conditions of juglone pre-treatment. The expression levels of Pin1, GDNF, and ANG II were notably elevated on 7-, and 10- days post-wound compared to those measured on 3-day. Contrastingly, pre-treatment with juglone significantly inhibited the expression of these molecules. Histological analyses, including HE (Hematoxylin and Eosin), Masson’s trichrome, and EVG (Elastic van Gieson) staining, demonstrated that vascular angiogenesis, as well as collagen and elastin deposition, were substantially reduced in the juglone pre-treated group when compared to the normal group. Further, immunohistochemical analysis revealed a considerable decrease in CD31 expression in the juglone pre-treatment group relative to the normal control group. Pin1 serves as a pivotal facilitator of wound repair. The findings indicate that the modulation of Pin1, GDNF, and ANG II expression impacts the wound healing process in rats, suggesting potential targets for therapeutic intervention in human wound repair. [ABSTRACT FROM AUTHOR]

Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy. [ABSTRACT FROM AUTHOR]

• EAF2 plays a key role in human malignancies. • EAF2 expression was closely associated with the immune-infiltrating levels of immune cells. • EAF2 has a strong positive correlation with CD19, implying they may be functional partners in the immune response of SKCM. • EAF2 could be a promising and potential biomarkers for the diagnosis and immunotherapy in patients with melanoma. Skin cutaneous melanoma (SKCM) accounts for over 75% of skin cancer-related deaths each year. EAF2, as a member of EAF family, has been found in several cancers, however, the role of EAF2 in SKCM is rarely studied. In this study, we utilized multiple bioinformatics tools to systematically analyze the expression of EAF family and investigate the prognostic value of EAF2 in melanoma. We found both transcriptional and proteomics expression expressions of EAF2 were elevated in SKCM. Survival analysis and ROC curves showed significant diagnostic and prognostic ability of EAF2. Importantly, EAF2 expression was closely associated with the immune-infiltrating levels of B cells, CD4+ T, CD8+ T, neutrophils, macrophages and dendritic cells. Co-expression analysis showed EAF2 has a strong positive correlation with CD19, implying they may be functional partners in the immune response of SKCM. In summary, our study is the first to reveal that increased expression of EAF2 is significantly correlated with tumor progression and better prognosis in SKCM patients. The role of EAF2 in SKCM demonstrated that it might be a potential and promising biomarker for the diagnosis and prediction of prognosis in patients with SKCM. [ABSTRACT FROM AUTHOR]

Background: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. Methods: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. Results: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators. Conclusion: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment. [ABSTRACT FROM AUTHOR]

The triethylamine promoted three-component reaction of N-(4-nitrobenzyl), N-ethoxycarbonylmethylisoquinolinium bromide, isatins and malononitrile in ethanol afforded spiro[indoline-3,2′-pyrrolo[2,1-a]isoquinolines] in good yields and with high diastereoselectivity. The similar reaction of N-cyanomethylisoquinolinium chloride mainly gave complex indolo[2″,3″:2′,3′]pyrrolo[3′,4′:4,5]pyrrolo[2,1-a]isoquinoline derivatives. However, the three-component reaction of N-cyanomethylisoquinolinium chloride, isatins and ethyl cyanoacetate mainly resulted in functionalized spiro[indoline-3,8′-pyrido[2′,3′:4,5]pyrrolo[2,1-a]isoquinolines]. [ABSTRACT FROM AUTHOR]

A graphical abstract of the study "Synthesis of Densely Substituted Dispirocyclopentanebisoxindoles by Base Promoted Sequential Reaction of Two Different 3-Methyleneoxindoles With Thiol" by Guo-Liang Shen and colleagues is presented.

An efficient protocol for the diastereoselective synthesis of the title compounds by 1,3-dipolar cycloaddition of N-phenacylbenzothiazolium and N-phenacylthiazolium bromides with several oxindoles is reported. [ABSTRACT FROM AUTHOR]

Purpose: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. Methods: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). Result: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80–1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88–1.70, P = 0.238). Conclusion: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection. [ABSTRACT FROM AUTHOR]

Abstract: Triethylamine promoted cycloaddition reaction of N‐alkoxycarbonylmethylquinolinium bromide with isatylidene malononitriles afforded diastereoisomeric spiro[indoline‐3, 2′‐pyrrolo[1, 2‐a]quinolines] in satisfactory yields. The similar 1,3‐dipolar cycloaddition with N‐(p‐nitrobenzyl)quinolinlium bromide gave spiro[indoline‐3, 2′‐pyrrolo[1, 2‐a]quinolines] in good yields and with high diastereoselectivity. More importantly, the sequential cycloaddition reaction and oxidation reaction with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) resulted in novel 2‐(2‐oxoindolin‐3‐ylidene)‐2‐(2‐(dicyanomethylene)quinolin‐1‐yl)acetates. [ABSTRACT FROM AUTHOR]

An abstract on the domino cycloaddition reactions of N-benzylbenzimidazolium salts with oxoindolin and ylidene acetates is presented.

Necrotizing fasciitis (NF) has emerged as rare but rapidly progressive, life-threatening severe skin and soft tissue infection. We conducted a study to investigate whether Th1/Th2 cytokines could serve as biomarkers to distinguish NF from class III skin and soft tissue infections (SSTIs). A retrospective review was performed for 155 patients suffering from serious skin and soft tissue infections from October 2020 to February 2022. Th1/Th2 cytokines were obtained from peripheral blood and wound drainage fluid samples. Data on demographic characteristics, causative microbiological organisms, Th1/Th2 cytokines, c-reactive protein, procalcitonin and white blood cell (WBC) were extracted for analysis. Factors with statistical difference(p < 0.1) were included in the multivariate logistic regression model. The clinical differential diagnostic values of interleukin-2(IL-2), IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-r (IFN-r) were analyzed by receiver operating characteristic (ROC) curve. Among the 155 patients, 66(43%) patients were diagnosed as NF. We found no significant difference for sex, age, location of infection, coexisting condition, predisposition, duration of symptoms before admission and micro-organisms, WBC, procalcitonin and c-reactive protein in NF and class III SSTIs group. NF had higher levels of IL-6 in serum (50.46 [24.89, 108.89] vs. 11.87 [5.20, 25.32] pg/ml; p＜0.01), IL-10 in serum (3.45 [2.03, 5.12] vs. 2.51 [1.79, 3.29] pg/ml; p＜0.01), IL-2 in wound drainage fluid (0.89 [0.49, 1.33] vs. 0.63 [0.14, 1.14] pg/ml; p = 0.02), IL-6 in wound drainage fluid (5000.84 [1392.30, 13287.19] vs. 1927.82 (336.65, 6759.27) pg/ml; p＜0.01), TNF-a in wound drainage fluid (5.20 [1.49, 22.97] vs. 0.96 [0.12, 3.21] pg/ml; p＜0.01) and IFN-r in wound drainage fluid (1.32 [0.47, 4.62] vs. 0.68 [0.10, 1.88] pg/ml; p = 0.02) as compared to the class III SSTIs. Multivariate logistic regression analyses showed that IL-6 in serum, IL-10 in serum and TNF-a in wound drainage fluid exhibited independently significant associations with diagnosis of NF(p＜0.05). In ROC curve analysis of IL-2, IL-6, IL-10, TNF-a and IFN-r for diagnosis of NF, the area under the curve (AUC) of IL-6 in serum could reach to 0.80 (p＜0.001). Using 27.62 pg/ml as the cut off value, the sensitivity was 74% and the specificity was 79% in IL-6 in serum. Th1/Th2 cytokines, IL-6 in serum in particular, are potential biomarkers for the diagnosis of NF in the early stage. However, larger patient populations with multiple centers and prospective studies are necessary to ensure the prognostic role of Th1/Th2 cytokines. • Th1/Th2 cytokines could be a potential diagnostic tool for NF in the early stage. • IL-6 in serum had the best diagnostic value for NF. • Larger patient populations and prospective studies are necessary to ensure the prognostic role of Th1/Th2 cytokines. [ABSTRACT FROM AUTHOR]

Background: Inadequate preoperative management of chronic medications can place perioperative patients at risk and cause unnecessary delays in surgical procedures. This study aims to investigate the prevalence of chronic medication therapy problems (CMTPs) in hospitalized perioperative patients and assess the relevance of pharmacists' interventions. Methods: We conducted a retrospective study of pharmacist-led preoperative management of chronic medications in hospitalized adult patients from November 2018 to April 2019. The recorded drug-related problems (DRPs) were retrospectively reviewed and categorized according to the Pharmaceutical Care Network Europe classification V9.1 and were analyzed with a multinomial regression model to identify risk factors. Results: A total of 254 DRPs were recorded, with an average of 0.52 DRPs per patient. Treatment safety (66.9%) was the most common DRP. The most frequent causes of perioperative DRPs and nonperioperative DRPs were drug selection (72.9%) and patient related (50.8%), respectively. Of the 292 documented interventions, 71.6% were fully accepted by the clinicians and patients. The majority (68.9%) of the recorded problems were completely resolved. The number of comorbidities (OR = 3.815) and the number of chronic medications taken (OR = 1.539) were risk factors for the occurrence of DRPs. Conclusion: The findings of this study suggest that pharmacist-led chronic medication therapy management in surgical wards may be an effective method to help reduce medication-related surgical risks and optimize the medication therapies used for the long-term treatment of chronic diseases. [ABSTRACT FROM AUTHOR]

Keratins (KRTs), the intermediate filament-forming proteins of epithelial cells, are extensively used as diagnostic biomarkers in cancers and associated with tumorigenesis and metastasis in multiple cancers. However, the diverse expression patterns and prognostic values of KRTs in melanoma have yet to be elucidated. In the current study, we examined the transcriptional and clinical data of KRTs in patients with melanoma from GEO, TCGA, ONCOMINE, GEPIA, cBioPortal, TIMER and TISIDB databases. We found that the mRNA levels of KRT1/2/5/6/8/10/14/15/16/17 were significantly differential expressed between primary melanoma and metastatic melanoma. The expression levels of KRT1/2/5/6/10/14/15/16/17 were correlated with advanced tumor stage. Survival analysis revealed that the high transcription levels of KRT1/5/6/14/15/16/17 were associated with low overall survival in melanoma patients. GSEA analysis indicated that the most involved hallmarks pathways were P53 pathway, KRAS signaling, estrogen response early and estrogen response late. Furthermore, we found some correlations among the expression of KRTs and the infiltration of immune cells. Our study may provide novel insights for the selection of prognostic biomarkers for melanoma. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing attention from the last decades. This study focused on comprehensive identification, validation, and functional annotations of prognostic differentially expressed genes (DEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. DEGs were obtained using three chip datasets from GEO database to identify after standardization annotation. A total of 73 DEGs were identified as possible candidate prognostic biomarkers between melanocytic nevus and malignant melanoma. In addition, survival curves indicated that six hub genes, including FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2, were significant prognostic signatures for CM and of significant value to predict transformation from nevi to melanoma. Furthermore, immunohistochemistry staining was performed to validate differential expression levels and prognostic implications of six hub genes between CM tissue and nevus tissues from the First Affiliated Hospital of Soochow University cohort. It suggested that significantly elevated FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 proteins expressed in the CM than in the nevus tissues. Functional enrichment and significant pathways of the six significant hub genes indicated that the mostly involved hallmarks include the P53 pathway, K-ras signaling, estrogen response late, and estrogen response early. In summary, this study identified significant DEGs participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 provided clues of prognostic implications, which might help us evaluate malignant potential of nevus and underlying carcinogenesis progress from melanocytic nevus to melanoma. [ABSTRACT FROM AUTHOR]

Background: Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers, causing about 72% of deaths in skin carcinoma. Although extensive study has explored the mechanism of recurrence and metastasis, the tumorigenesis of cutaneous melanoma remains unclear. Exploring the tumorigenesis mechanism may help identify prognostic biomarkers that could serve to guide cancer therapy. Method: Integrative bioinformatics analyses, including GEO database, TCGA database, DAVID, STRING, Metascape, GEPIA, cBioPortal, TRRUST, TIMER, TISIDB and DGIdb, were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of SKCM. Furthermore, immunohistochemistry (IHC) staining was performed to validate differential expression levels of hub genes between SKCM tissue and normal tissues from the First Affiliated Hospital of Soochow University cohort. Results: A total of 308 differentially expressed genes (DEGs) and 12 hub genes were found significantly differentially expressed between SKCM and normal skin tissues. Functional annotation indicated that inflammatory response, immune response was closely associated with SKCM tumorigenesis. KEGG pathways in hub genes include IL-10 signaling and chemokine receptors bind chemokine signaling. Five chemokines members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) were associated with better overall survival and pathological stages. IHC results suggested that significantly elevated CXCL9, CXCL10, CXCL13, CCL4 and CCL5 proteins expressed in the SKCM than in the normal tissues. Moreover, our findings suggested that IRF7, RELA, NFKB1, IRF3 and IRF1 are key transcription factors for CCL4, CCL5, CXCL10. In addition, the expressions of CXCL9, CXCL10, CXCL13, CCL4 and CCL5 were positively correlated with infiltration of six immune cells (B cell, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells) and 28 types of TILs. Among them, high levels of B cells, CD8+T cells, neutrophils and dendritic cells were significantly related to longer SKCM survival time. Conclusion: In summary, this study mainly identified five chemokine members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) associated with SKCM tumorigenesis, progression, prognosis and immune infiltrations, which might help us evaluate several immune-related targets for cutaneous melanoma therapy. [ABSTRACT FROM AUTHOR]