Surgical outcomes of gastro-entero-pancreatic neuroendocrine tumors G3 versus neuroendocrine carcinoma.

BACKGROUND: To define surgical outcomes of patients with high-grade gastro-entero-pancreatic neuroendocrine neoplasm grade G3 (GEP-NEN G3). METHODS: Patients who underwent surgical resection between 2000 and 2016 were identified. The overall survival (OS) and recurrence-free survival (RFS) of patients with gastro-entero-pancreatic neuroendocrine tumors grade G3 (GEP-NET G3) versus neuroendocrine carcinoma (NEC) were evaluated. RESULTS: Fifty-one out of 2182 (2.3%) patients who underwent surgical resection were diagnosed as GEP-NEN G3. The pancreas was the most common primary site (n = 3772.5%). A majority of patients had lymph node metastasis (n = 3262.7%); one in three (n = 1631.4%) had distant metastasis. The median OS and RFS of the entire cohort were 56.4 and 34.5 months, respectively. Perineural invasion was a strong prognostic factor associate with OS after surgical resection. Patients with NEC had a worse survival outcome versus patients with NET G3 (median OS: 33.1 months vs. not attained, p = 0.088). In contrast, among patients who underwent curative-intent resection, patients with NEC had comparable RFS versus patients with NET G3 (median RFS: 35.6 vs. 33.9 months, p = 0.774). CONCLUSIONS: Surgical resection provided acceptable short- and long-outcomes for well-selected patients with resectable GEP-NEN G3. NEC was associated with a worse OS versus NET G3.

Individualized Whole Course Nutrition Management for Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs. METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group. RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05). CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.

Establishment and evaluation of a CT-based radiomic model for AIDS-associated pulmonary cryptococcosis.

BACKGROUND: Establish a CT-based diagnostic radiomic model for AIDS complicated with pulmonary cryptococcosis and evaluate the diagnostic efficacy of this model. METHODS: This retrospective study enrolled 98 AIDS patients with pulmonary cryptococcosis and 103 AIDS patients with other infections or neoplastic lesions, comprising a total of 699 lesions. Patients were randomly divided into a training group and test group at a ratio of 2.75:1. Features from all lesions, cavity lesions and solid nodule lesions were extracted, and two kinds of radiomic models (6 types) were established. ROC curves were drawn, and the sensitivity and specificity were calculated to compare the SVM model and LR model, radiologists' empirical diagnoses and the combination of these empirical diagnoses with the radiomic model. RESULTS: The AUCs of senior radiologist for all lesions and cavity lesions were lower than those of the SVM and LR models. The diagnostic efficacy of primary radiologist was lower than that of both of the other model types. The diagnostic efficacy of the LR model was relatively stable, with the highest diagnostic efficiency of the 3 model/radiologist groups. The AUCs of intermediate radiologist in combination with the LR radiomic model for all lesions, nodular lesions and cavity lesions were 0.88, 0.84, and 0.9, respectively, which were the highest among all models and radiologists. CONCLUSIONS: The CT-based radiomic LR model of AIDS-associated pulmonary cryptococcosis exhibits good diagnostic performance, which was similar to that of senior radiologists and higher than that of the primary radiologist. With the help of a radiomic model, radiologists can achieve improved diagnostic accuracy compared to that when only an empirical diagnosis is used.

Shark mouth pancreaticojejunostomy reduced the rate of clinically related pancreatic fistula: a historic cohort comparative analysis.

BACKGROUND: A novel procedure called shark mouth pancreaticojejunostomy (SMP) was developed, for the reconstruction of the pancreatic stump which has a theoretical advantage for anastomosis healing and wide applicability. METHODS: A comparative study of the patients who underwent SMP (SMP cohort) and those who underwent end-to-end dunking pancreaticojejunostomy (historic cohort) at Peking University Third Hospital was conducted. Each group was analyzed for the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) and morbidities. RESULTS: The clinicopathological data of 151 patients from the SMP cohort and 82 patients from the historic cohort were analyzed. In the SMP group, the rate of CR-POPF was 7.3% (11/151), which was significantly lower than the rate of CR-POPF in the historic group as 19.5% (16/82) (P = 0.005). The primary results were unaffected by sensitivity analyses based on several risk factors for CR-POPF. The rates of morbidities besides CR-POPF were 15.9% (24/151) in the SMP group and 17.1% (14/82) in the historic cohort (P = 0.194). The principal results were not changed by the propensity score matched (PSM) analysis. CONCLUSION: SMP is a safe and simple surgical procedure for the reconstruction of the pancreatic stump compared with end-to-end dunking pancreticojejunostomy.

[Effect of Social Support on Multimorbidity and Related Outcomes of Middle-Aged and Older Adults in China].

Objective: To analyze the current status of social support for middle-aged and older adults with multimorbidity and to explore the correlation between different dimensions of social support and multimorbidity and the related outcomes on the basis of China Health and Retirement Longitudinal Study (CHARLS) 2015 survey data so as to reveal the complex social background of multimorbidity and the impact of social support on multimorbidity. Methods: A total of 9168 valid samples, with an average age of 59.60 years, were included in the study. Using the social support-related variables of the respondents, we conducted factor analysis and constructed regression models of common factors of social support and multimorbidity-related outcomes, intending to analyze the impact of common factors of social support on multimorbidity in the middle-aged and older adults. Results: The multimorbidity of middle-aged and older adults in China was related to multiple factors of social support, and the differences were statistically significant. Logistic regression showed that social support in the form of activity/recreational facilities and medical resources was a protective factor of multimorbidity, that family emotional support and economic support had a positive effect on life satisfaction of comorbid patients, and that social support in the form of education, social life and housing conditions was negatively correlated with catastrophic medical expenditure of the comorbid population ( P<0.05). Conclusion: Social support for middle-aged and older adults in China is unevenly distributed. Social support in the form of activity/recreational facilities and medical resources may reduce the risks of multimorbidity among middle-aged and older adults. Good family economic and emotional support can improve the life satisfaction of middle-aged and older adults with multimorbidity. Social support in the form of education, social life and housing conditions may reduce the risk of catastrophic medical expenditure in middle-aged and older adults with multimorbidity.

KLHDC7B-DT aggravates pancreatic ductal adenocarcinoma development via inducing cross-talk between cancer cells and macrophages.

Tumor microenvironment (TME) exerts key roles in pancreatic ductal adenocarcinoma (PDAC) development. However, the factors regulating the cross-talk between PDAC cells and TME are largely unknown. In the present study, we identified a long noncoding RNA (lncRNA) KLHDC7B divergent transcript (KLHDC7B-DT), which was up-regulated in PDAC and correlated with poor survival of PDAC patients. Functional assays demonstrated that KLHDC7B-DT enhanced PDAC cell proliferation, migration, and invasion. Mechanistically, KLHDC7B-DT was found to directly bind IL-6 promoter, induce open chromatin structure at IL-6 promoter region, activate IL-6 transcription, and up-regulate IL-6 expression and secretion. The expression of KLHDC7B-DT was positively correlated with IL-6 in PDAC tissues. Via inducing IL-6 secretion, KLHDC7B-DT activated STAT3 signaling in PDAC cells in an autocrine manner. Furthermore, KLHDC7B-DT also activated STAT3 signaling in macrophages in a paracrine manner, which induced macrophage M2 polarization. KLHDC7B-DT overexpressed PDAC cells-primed macrophages promoted PDAC cell proliferation, migration, and invasion. Blocking IL-6/STAT3 signaling reversed the effects of KLHDC7B-DT on macrophage M2 polarization and PDAC cell proliferation, migration, and invasion. In conclusion, KLHDC7B-DT enhanced malignant behaviors of PDAC cells via IL-6-induced macrophage M2 polarization and IL-6-activated STAT3 signaling in PDAC cells. The cross-talk between PDAC cells and macrophages induced by KLHDC7B-DT represents potential therapeutic target for PDAC.

[Subacute Thyroiditis Following HPV Vaccination: A Case Report].

Subacute thyroiditis (SAT) is the most common self-limiting thyroid disease causing pain. The etiology of the disease remains unknown, but it is usually related to viral infection or allergic reaction after viral infection. SAT after vaccination is extremely rare. The patient had a fever of no clearly defined cause about 8 hours after receiving the first dose of a 0.5 mL 9-valent human papillomavirus vaccine (Gardasil 9). The highest temperature was 37.8 ℃, accompanied by a pain in the neck, fatigue and the increasing pain when swallowing. After the patient was admitted to the hospital, physical examination revealed Ⅱ° enlargement of the thyroid gland, which was hard and tender, and no vascular murmur was heard. There was no redness, swelling or ulceration at the vaccination site, and no obvious abnormalities were observed in other physical examinations. Laboratory findings were as follows: C-reactive protein, 25.20 mg/L; erythrocyte sedimentation rate, 55 mm/1 h; leukocyte, 4.94×10 9 L -1; thyrotropin, 0.137 mU/L; free thyroxine, 22.32 pmol/L; antithyroglobulin antibody, 69.18 IU/mL; anti-thyroid peroxidase antibody, 21.66 IU/mL. Thyroid ultrasonography showed diffuse enlargement of bilateral thyroid with uneven internal echo. The patient was diagnosed with SAT. After 5 days of treatment with ibuprofen, the patient no longer had low fever and the neck pain was relieved. The patient was followed up till now, and had completed the vaccination of the three-dose 9-valent human papillomavirus vaccine. The function of thyroid was found to be normal in follow-up visits, and SAT did not recur.

Structural and Functional Insights into PpgL, a Metal-Independent ß-Propeller Gluconolactonase That Contributes to Pseudomonas aeruginosa Virulence.

Biofilm formation is a critical determinant in the pathopoiesis of Pseudomonas aeruginosa It could significantly increase bacterial resistance to drugs and host defense. Thus, inhibition of biofilm matrix production could be regarded as a promising attempt to prevent colonization of P. aeruginosa and the subsequent infection. PpgL, a periplasmic gluconolactonase, has been reported to be involved in P. aeruginosa quorum-sensing (QS) system regulation. However, the detailed function and catalysis mechanism remain elusive. Here, the crystal structure of PpgL is described in the current study, along with biochemical analysis, revealing that PpgL is a typical ß-propeller enzyme with unique metal-independent lactone hydrolysis activity. Consequently, comparative analysis of seven-bladed propeller lactone-catalyzing enzymes and mutagenesis studies identify the critical sites which contribute to the diverse catalytic and substrate recognition functions. In addition, the reduced biofilm formation and attenuated invasion phenotype resulting from deletion of ppgL confirm the importance of PpgL in P. aeruginosa pathogenesis. These results suggest that PpgL is a potential target for developing new agents against the diseases caused by P. aeruginosa.

Absolute Configuration of Bioactive Azaphilones from the Marine-Derived Fungus Pleosporales sp. CF09-1.

Investigation of the marine-derived fungus Pleosporales sp. CF09-1 cultured in modified PDB medium led to the isolation of six new azaphilone derivatives, pleosporalones B and C (1 and 2) and pleosporalones E-H (4-7), and one known analogue (3). The absolute configurations of C-2' and C-3' in 3 were assigned by a vibrational circular dichroism method. The C-11 relative configurations for the pair of C-11 epimers (4 and 5) were established by comparing the magnitude of the computed 13C NMR chemical shifts (Δδcalcd) with the experimental 13C NMR values (Δδexp) for the epimers. Antiphytopathogenic and anti- Vibrio activities were evaluated for 1-7. Pleosporalone B (1) exhibited potent antifungal activities against the fungi Alternaria brassicicola and Fusarium oxysporum with the same MIC value of 1.6 µg/mL, which were stronger than the positive control ketoconazole among these compounds. Additionally, pleosporalone C (2) displayed significant activity against the fungus Botryosphaeria dothidea (MIC, 3.1 µg/mL). Compounds 6 and 7 displayed moderate anti- Vibrio activities against Vibrio anguillarum and Vibrio parahemolyticus, with MIC values of 13 and 6.3 µg/mL for 6 and 6.3 and 25 µg/mL for 7, respectively.

Cisplatin inhibits the progression of bladder cancer by selectively depleting G-MDSCs: A novel chemoimmunomodulating strategy.

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues. There was a robust negative correlation between the G-MDSCs and the CD8+ T cells in the BC tissues. In this study, we attempted to identify pharmacological approaches to eliminate MDSCs and restore T cell anti-tumor activities. It is necessary to explore a method to eliminate the detrimental effects of MDSCs. Cisplatin, a chemotherapy medication used to treat BC, not only rapidly kills proliferating cancer cells but also affects the tumor immune microenvironment. However, the mechanism underlying this phenomenon is largely unknown. In this study, we found that Cisplatin directly inhibited the proliferation and induced the apoptosis of T24 cells (a BC cell line), as well as decreased the percentage of the G-MDSCs in the population of peripheral blood mononuclear cells (PBMCs), which restored the expansion of the CD8+ T cells. In the C3H/He mouse BC model, Cisplatin treatment inhibited the progression of BC and effectively decreased the proportion of G-MDSCs. These results suggest that Cisplatin treatment enhances the anti-tumor function of CD8+ T cells by decreasing G-MDSCs. This finding provides a new perspective for Cisplatin treatment to prevent the progression of BC, particularly in patients with abnormally high levels of G-MDSCs.

Predictive Factors for Differentiating Pancreatic Cancer-Associated Diabetes Mellitus from Common Type 2 Diabetes Mellitus for the Early Detection of Pancreatic Cancer.

BACKGROUND: The purpose of this study was to find the factors that may be helpful for differentiating pancreatic cancer-associated diabetes mellitus (PC + DM) from common type 2 diabetes for the early diagnosis of pancreatic cancer. METHODS: From January 2008 to August 2013, 171 patients with pancreatic cancer and new-onset diabetes were recruited for the study; 242 age- and gender-matched patients with common type 2 diabetes were also identified as control during the same period. The patient's characteristics and laboratory parameters were compared between the 2 groups. RESULTS: By multivariate logistic regression analysis, we found that body mass index (BMI), the age of onset of diabetes, hepatitis B virus (HBV) infection, total bilirubin (TBIL), alanine aminotransferase (ALT), creatinine (Cr), apolipoprotein-A1 (APO-A1), and white blood cell (WBC) were independent predictive factors for differentiating PC + DM from common type 2 diabetes; the areas under receiver operating characteristic curves were up to 0.815 for the combination of these 8 markers. CONCLUSIONS: These results suggest that BMI, the age of onset of diabetes, HBV infection, TBIL, ALT, Cr, APO-A1, and WBC are factors that could differentiate PC + DM from common type 2 -diabetes and may be used for early diagnosis of pancreatic cancer.

Prognostic value of the albumin-bilirubin grade in patients with hepatocellular carcinoma: Validation in a Chinese cohort.

AIM: The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh (C-P) score in predicting prognosis in this study. METHODS: The clinical data of 491 C-P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C-P score in predicting the short- and long-term clinical outcomes were compared. RESULTS: The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months, the 1-year, 3-year, and 5-year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C-P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test. CONCLUSIONS: The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well-designed studies with larger sample sizes are warranted.

Total tumor volume predicts survival following liver resection in patients with hepatocellular carcinoma.

Assessing the prognosis of patients with hepatocellular carcinoma (HCC) by the number and size of tumors is sometimes difficult. The main purpose of the study was to evaluate the prognostic value of total tumor volume (TTV), which combines the two factors, in patients with HCC who underwent liver resection. We retrospectively reviewed 521 HCC patients from January 2001 to December 2008 in our center. Patients were categorized using the tertiles of TTV. The prognostic value of TTV was assessed. With a median follow-up of 116 months, the 1-, 3-, and 5-year overall survival (OS) rates of the patients were 93.1 , 69.9, and 46.3 %, respectively. OS was significantly differed by TTV tertile groups, and higher TTV was associated with shorter OS (P < 0.001). Multivariate analysis revealed that TTV was an independent prognostic factor for OS. Larger TTV was significantly associated with higher alpha-fetoprotein level, presence of macrovascular invasion, multiple tumor lesions, larger tumor size, and advanced tumor stages (all P < 0.05). Within the first and second tertiles of TTV (TTV ≤ 73.5 cm(3)), no significant differences in OS were detected in patients within and beyond Milan criteria (P = 0.183). TTV-based Cancer of the Liver Italian Program (CLIP) score gained the lowest Akaike information criterion value, the highest χ (2) value of likelihood ratio test, and the highest C-index among the tested staging systems. Our results suggested that TTV is a good indicator of tumor burden in patients with HCC. Further studies are warranted to validate the prognostic value of TTV.

Long-term Outcomes of Sphincter-Saving Procedures for Diffuse Crohn's Disease of the Large Bowel.

BACKGROUND: Total abdominal colectomy with ileorectal anastomosis for Crohn's colitis is acceptable in the presence of a suitable rectum. Intentional IPAA has been proposed for diffuse Crohn's proctocolitis without enteric or anoperineal disease. OBJECTIVE: The aim of this study was to evaluate the long-term outcomes of sphincter-saving procedures for large-bowel Crohn's disease. DESIGN: Patients with preoperative Crohn's disease diagnosis undergoing intentional IPAA and ileorectal anastomosis were included. SETTINGS: The study was conducted at a tertiary care research center. PATIENTS: Ileorectal anastomosis was performed in 75 patients with Crohn's disease, whereas 32 patients underwent intentional IPAA. MAIN OUTCOME MEASURES: Long-term functional results and permanent stoma requirement of sphincter-saving operations were assessed. Quality of life and postoperative medication use were also compared with a control group of patients undergoing total proctocolectomy and end ileostomy. RESULTS: Patients undergoing ileorectal anastomosis were older and had longer disease duration, higher prevalence of perianal and penetrating disease, and history of small-bowel resection than those receiving IPAA. Indications for surgery, preoperative use of immunomodulators, and postoperative use of biologics were also significantly different. Although functional defecatory outcomes were comparable, reported quality of life 3 years after surgery was significantly better in patients who underwent IPAA than in patients with ileorectal anastomosis. Patients with IPAA were associated with significantly lower cumulative rates of surgical recurrence (HR = 0.28 (95% CI, 0.09-0.84); p = 0.017), indefinite stoma diversion (HR = 0.35 (95% CI, 0.13-0.99); p = 0.039), and proctectomy with end ileostomy (HR = 0.27 (95% CI, 0.07-0.96); p = 0.030) than those with ileorectal anastomosis. LIMITATIONS: The study was limited by its retrospective nature and small sample size. CONCLUSIONS: Contemporary patients selected to have intentional IPAA for Crohn's colitis have disease characteristics very different from those selected to have ileorectal anastomosis. Long-term follow-up confirms intentional IPAA as an acceptable option in selected patients with Crohn's colitis.

Impaction of surgical margin status on the survival outcome after surgical resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Conflicting results about the prognostic value of surgical margin status in patients with intrahepatic cholangiocarcinoma (ICC) have been reported. We aimed to assess the association between surgical margin status and prognosis in ICC through a meta-analysis. MATERIALS AND METHODS: We conducted a literature search of the articles evaluating the prognostic value of surgical margin status in patients with ICC. The pooled estimation of the hazard ratio (HR) with the 95% confidence interval (CI) was performed to determine the influence of surgical margin status on the survival outcome. RESULTS: A total of 21 studies involving 3201 patients were finally included into the meta-analysis. The percentage of patients with positive surgical margin ranged from 7.2% to 75.9% in the enrolled studies. The pooled estimates showed that patients with positive surgical margin had inferior overall survival (HR: 1.864; 95% CI: 1.542-2.252; P < 0.001) and progression-free survival (HR: 2.033; 95% CI: 1.030-4.011; P = 0.041) than patients with negative ones. The subgroup analyses and sensitivity analyses were consistent with the overall results. CONCLUSIONS: Patients with negative surgical margin had significantly favorable overall survival and progression-free survival after surgical resection for ICC. The notion of achieving the R0 resection should be emphasized.

Comparative metabolism of four limonoids in human liver microsomes using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry.

RATIONALE: Limonoids, characterized by a triterpenoid skeleton with a furan ring, are unique secondary metabolites widely distributed in the families of Rutaceae, particularly in Citrus species and Meliaceae. Studies on health benefits have demonstrated that limonoids have a range of biological activities. Dietary intake of citrus limonoids may provide a protective effect against the onset of various cancers and other xenobiotic related diseases. However, few studies about the metabolic profiles of limonoids have been carried out. METHODS: The objectives of this study were to investigate the metabolic profiles of four limonoids (limonin, obacunone, nominin and gedunin) in human liver microsomes (HLMs) using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC/HRMS) and to identify the cytochrome P450 (CYP) enzymes involved in the formation of their metabolites by recombinant human CYP enzymes. RESULTS: Based on the accurate HR-MS/MS spectra and the proposed MS/MS fragmentation pathways, four metabolites of limonin (M1-1, M1-2, M1-3 and M1-4), eight metabolites ofobacunone (M2-1, M2-2, M2-3, M2-4, M2-5, M2-6, M2-7 and M2-8), six metabolites of nominin (M3-1, M3-2, M3-3, M3-4, M3-5 and M3-6) and three metabolites of gedunin (M4-1, M4-2 and M4-3) in HLMs were tentatively identified and the involved CYPs were investigated. CONCLUSIONS: The results demonstrated that reduction at C-7 and C-16, hydroxylation and reaction of glycine with reduction limonoids were the major metabolic pathways of limonoids in HLMs. Among them, glycination with reduction was the unique metabolic process of limonoids observed for the first time. CYP2D6 and CYP3A4 played an important role in the isomerization and glycination of limonoids in HLMs, whereas other CYP isoforms were considerably less active. The results might help to understand the metabolic process of limonoids in vitro such as the unidentified metabolites of limonin glucoside observed in the medium of microbes and the biotransformation of limonin in juices. Moreover, it would be beneficial for us to further study the pharmacokinetic behavior of limonoids in vivo systematically.

Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis.

The prognostic role of inflammation index like neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta-analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression-free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499-2.193) and PFS (HR: 2.102, 95% CI: 1.554-2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226-2.022) and higher carcino-embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308-1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.

Ischemic preconditioning versus intermittent clamping of portal triad in liver resection: A meta-analysis of randomized controlled trials.

AIM: To compare the clinical outcome of patients undergoing liver resection under ischemic preconditioning (IP) versus intermittent clamping (IC). METHODS: A systematic published work search was conducted to detect randomized controlled trials (RCT) comparing IP and intermittent clamping of the portal triad. A meta-analysis was conducted to estimate postoperative morbidity and mortality, blood loss, transfusion requirement, and liver injury based on the levels of bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Meta-analysis was performed using either the fixed-effects model or random-effects model. RESULTS: Five RCT published between 2006 and 2012 containing a total of 403 patients were eligible for final analysis. Meta-analysis of operative time showed it was lower in the IP group than the IC group with weighted mean difference (WMD) of -18.23 (95% confidence interval (CI), -28.58 to -7.87; P = 0.0006). Meta-analysis of ALT levels indicated lower levels in the IP group on postoperative days 3 and 7 (WMD on day 3: -45.27, 95% CI, -49.92 to -40.62; P < 0.00001; I(2) = 0%; WMD on day 7: -24.33, 95% CI, -28.04 to -20.62; P < 0.00001; I(2) = 0%). Meta-analyses revealed no significant difference in blood loss, transfusion requirement, mortality, morbidity, ischemic duration, hospital stay, AST and bilirubin levels on postoperative days 1, 3 and 7, and ALT levels on postoperative day 1 between IP and IC groups. CONCLUSION: On currently available evidence, IP does not offer a satisfying benefit to patients undergoing hepatic resection. However, they have lower operative time and less liver injury after liver resections.

Systemic immune-inflammation index and all-cause and cause-specific mortality in sarcopenia: a study from National Health and Nutrition Examination Survey 1999-2018.

Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort. Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness. Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models. Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.

Design and Synthesis of Novel Diphenyl Ether Carboxamide Derivatives To Control the Phytopathogenic Fungus Sclerotinia sclerotiorum.

Sclerotinia stem rot (SSR) caused by the phytopathogenic fungus Sclerotinia sclerotiorum has led to serious losses in the yields of oilseed rape and other crops every year. Here, we designed and synthesized a series of carboxamide derivatives containing a diphenyl ether skeleton by adopting the scaffold splicing strategy. From the results of the mycelium growth inhibition experiment, inhibition rates of compounds 4j and 4i showed more than 80% to control S. sclerotiorum at a dose of 50 µg/mL, which is close to that of the positive control (flubeneteram, 95%). Then, the results of a structure-activity relationship study showed that the benzyl scaffold was very important for antifungal activity and that introducing a halogen atom on the benzyl ring would improve antifungal activity. Furthermore, the results of an in vitro activity test suggested that these novel compounds can inhibit the activity of succinate dehydrogenase (SDH), and the binding mode of 4j with SDH was basically similar to that of the flutolanil derivative. Morphological observation of mycelium revealed that compound 4j could cause a damage on the mycelial morphology and cell structure of S. sclerotiorum, resulting in inhibition of the growth of mycelia. Furthermore, in vivo antifungal activity assessment of 4j displayed a good control of S. sclerotiorum (>97%) with a result similar to that of the positive control at a concentration of 200 mg/L. Thus, the diphenyl ether carboxamide skeleton is a new starting point for the discovery of new SDH inhibitors and is worthy of further development.