Oxidative Cross-Coupling of α-Amino Ketones with Alcohols Enabled by I2-Catalyzed C-H Hydroxylation.

An I2-catalyzed oxidative cross-coupling of α-amino ketones with a wide range of alcohols is described. Using a combination of air and dimethyl sulfoxide (DMSO) as oxidants, the protocol allows an efficient synthesis of α-carbonyl N,O-acetals with high functional group tolerance and enables the late-stage introduction of α-amino ketones into biorelevant alcohols. Moreover, the present method can be used in the coupling of α-amino ketones with other kinds of nucleophiles, which demonstrates great generality for the functionalization of α-amino ketones. A preliminary mechanistic investigation suggests that C-H hydroxylation of α-amino ketones has been recognized as the key step followed by subsequent dehydration coupling.

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives.

Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.

Prognostic value of perioperative serum low-density lipoprotein cholesterol level for postoperative prognosis of pancreatic cancer: a retrospective study.

BACKGROUND: As a common malignant tumour, pancreatic cancer (PC) has the worst clinical outcome. Early evaluation of the postoperative prognosis has certain clinical value. Low-density lipoprotein cholesterol (LDL-c), which is mainly composed of cholesteryl esters, phospholipids, and proteins, plays an important role in transporting cholesterol into peripheral tissues. LDL-c has also been reported to be correlated with the occurrence and progression of malignant tumours and can predict postoperative prognosis in various tumours. AIMS: To determine correlation between serum LDL-c level and clinical outcome in PC patients after surgery. METHODS: Data of PC patients that received surgery at our department from January 2015 to December 2021 were retrospectively analysed. Receiver operating characteristic (ROC) curves between perioperative serum LDL-c at different timepoints and survival rate at postoperative 1-year were drawn, and the optimal cut-off value was calculated. Patients were categorized into low and high LDL-c groups, and their clinical data and outcome were compared. Univariate and multivariate analyses were applied to screen out risk markers for poor prognosis of PC patients after surgery. RESULTS: The area under the ROC curve of serum LDL-c at 4 weeks after surgery and prognosis was 0.669 (95% CI: 0.581-0.757), and the optimal cut-off value was 1.515 mmol/L. The median disease-free survival (DFS) rates of low and high LDL-c groups were 9 months and 16 months, respectively, and the 1-, 2- and 3-year DFS rates were 42.6%, 21.1% and 11.7% in low LDL-c group, respectively, and, 60.2%, 35.3% and 26.2% in high LDL-c group, respectively (P = 0.005). The median overall survival (OS) rates of low and high LDL-c groups were 12 months and 22 months, respectively, and the 1-, 2- and 3-year OS rates were 46.8%, 22.6% and 15.8% in low LDL-c group, respectively, and 77.9%, 46.8% and 30.4% in high LDL-c group, respectively (P = 0.004). Multivariate analysis confirmed low postoperative 4-week serum LDL-c as independent risk marker for early tumour recrudesce and poor clinical outcome in PC patients. CONCLUSION: High postoperative 4-week serum LDL-c is a prognostic marker for prolonged DFS and OS time in PC patients.

Utilizing bifurcated allogeneic vein grafts: a novel approach for preventing sinistral portal hypertension following Pancreaticoduodenectomy. a 10-year before and after study.

BACKGROUND: Sinistral portal hypertension (SPH) may occurs in patients with pancreatic carcinoma after pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) cofluence resection. This study aimed to evaluate outcomes with the bifurcated allogeneic vein replacement in the prevention of SPH in pancreatic carcinoma patients. MATERIALS AND METHODS: A total of 81 patients were included. We retrospectively collected clinicopathological data from 66 patients underwent PD with S-M-P confluence resection in our hospital from Jan. 2011 to Dec. 2021, compared the correlation between different venous reconstruction methods using log-rank tests and clinical outcomes through univariate and multivariate analyses. Secondly, we prospectively collected clinical data and outcomes of 15 patients who underwent splenic vein reconstruction from Jan. 2021 to Jan. 2023. RESULTS: In the retrospective study, 43 cases received reconstruction by bifurcated allogeneic vein (Reconstruction group) and 23 cases received simply SV ligation (Ligation group). The preoperative platelet counts and spleen volume were similar between two groups (P>0.05). Nevertheless, at 1 month, 3 months and 6 months after operation, the related indexes of SPH such as platelet count, spleen volume, spleen volume ratio and esophagogastric varices (EGV) grade in Reconstruction group were better than those in Ligation group (P<0.05). 6 months after surgery, the incidence of SPH in Ligation group was significantly higher than in Reconstruction group (36.4% vs. 8.1%, respectively). In the prospective study, the incidence of SPH in patients undergoing SV reconstruction was 6.7% (1/15). CONCLUSION: Without compromising surgical outcomes, reconstruction of the S-M-P confluence by bifurcated allogeneic vein is a better method to avoid SPH in patients with advanced pancreatic carcinoma.

Anti-PD-1 therapy reverses TIGIT+CD226+NK depletion in immunotherapy resistance of hepatocellular carcinoma through PVR/TIGIT pathway.

Immunotherapy resistance conducts the main reason for failure of PD-1-based immune checkpoint inhibitors (ICIs) in patients with hepatocellular carcinoma (HCC). This study aims to clarify the mechanism of nature kill cells (NK) depletion in immunotherapy resistance of HCC. Cancerous /paracancerous tissues and peripheral blood (PB) of 55 HCC patients were collected and grouped according to differentiation degree, FCM, IHC and lymphocyte culture drug intervention experiments were used to determine NK cell depletion degree. Furthermore, a mouse model of HCC in situ was constructed and divided into different groups according to intervention measures of ICIs. Immunofluorescence thermography was used to observe changes in tumor burden. NK cells in cancerous tissues significantly up-regulated TIGIT expression (P < 0.001). Intervention experiments revealed that TIGIT and PD-1 expression decreased gradually with increased PD-1 inhibitor dose in moderately-highly differentiated patients (P < 0.05). Animal experiment showed that tumors proliferation in experimental group was inhibited after PD-1 blockage, WB indicated that ICIs decreased TIGIT and PVRL1 protein expression while increased CD226 and PVRL3 protein expression. We concluded that TIGIT+NK cells competitively bind to PVR with CD226 and promote NK cell depletion. Anti-PD-1 decreases PVRL1 expression through PD-1/PD-L1 pathway, reducing the PVR/TIGIT inhibitory signal pathway, and enhancing function of PVR/CD226 activation signal.

Covalent conjugation of proteins onto fluorescent single-walled carbon nanotubes for biological and medical applications.

Single-walled carbon nanotubes (SWCNTs) have optical properties that are conducive for biological applications such as sensing, delivery, and imaging. These applications necessitate the immobilization of macromolecules that can serve as therapeutic drugs, molecular templates, or modulators of surface interactions. Although previous studies have focused on non-covalent immobilization strategies, recent advances have introduced covalent functional handles that can preserve or even enhance the SWCNT optical properties. This review presents an overview of covalent sidewall modifications of SWCNTs, with a focus on the latest generation of "sp3 defect" modifications. We summarize and compare the reaction conditions and the reported products of these sp3 chemistries. We further review the underlying photophysics governing SWCNT fluorescence and apply these principles to the fluorescence emitted from these covalently modified SWCNTs. Finally, we provide an outlook on additional chemistries that could be applied to covalently conjugate proteins to these chemically modified, fluorescent SWCNTs. We review the advantages of these approaches, emerging opportunities for further improvement, as well as their implications for enabling new technologies.

Allogeneic Vessels in Pancreaticoduodenectomy with Portal Vein Resection: Risk of Portal Vein Thrombosis and Prognosis.

BACKGROUND: Allogeneic vessels (AV) are commonly used in pancreaticoduodenectomy (PD) with portal vein resection (PVR), but the epidemiological characteristics of portal vein thrombosis (PVT) are still unclear. METHODS: The clinicopathological data of patients who underwent PD combined with PVR in our hospital from January 2011 to October 2022 were retrospectively collected. All patients underwent regular contrast-enhanced CT of the abdomen after surgery to identify PVT or recurrence and metastasis of the tumor. RESULTS: A total of 878 patients received PD, of which 213 patients who also underwent PVR were included in the study. Among them are 16 (7.5%) tangential/patch reconstructions, 51 (23.9%) end-to-end anastomosis, and 146 (68.5%) AV reconstructions. The cumulative incidence of PVT in 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years after surgery was 0.9%, 7.3%, 7.3%, 15.9%, 23.4%, and 27.6%, respectively. The results of logistic regression analysis showed that diabetes, operation procedure, and AV reconstruction were independent risk factors for PVT (P < 0.05). In the Cox analysis, PVT was clearly correlated with tumor recurrence (P = 0.038, hazard ratio (HR) = 1.553) and overall survival (P = 0.044, HR = 1.592) of pancreatic cancer patients. CONCLUSION: The prevalence of PVT is high in PD with PVR, particularly in patients undergoing AV reconstructions. The occurrence of PVT has a clear correlation with the patient's long-term prognosis.

A nomogram model to predict the portal vein thrombosis risk after surgery in patients with pancreatic cancer.

Background: Portal vein thrombosis (PVT) is a common postoperative complication in patients with pancreatic cancer (PC), significantly affecting their quality of life and long-term prognosis. Our aim is to establish a new nomogram to predict the risk of PVT after PC surgery. Method: We collected data from 416 patients who underwent PC surgery at our hospital between January 2011 and June 2022. This includes 87 patients with PVT and 329 patients without PVT. The patients were randomly divided into a training group and a validation group at a ratio of 7:3. We constructed a nomogram model using the outcomes from both univariate and multivariate logistic regression analyses conducted on the training group. The nomogram's predictive capacity was assessed using calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: In the study, the prevalence of PVT was 20.9%. Age, albumin, vein reconstruction and preoperative D-dimer were independent related factors. The model achieved a C-index of 0.810 (95% confidence interval: 0.752-0.867), demonstrating excellent discrimination and calibration performance. The area under the ROC curve of the nomogram was 0.829 (95% CI: 0.750-0.909) in the validation group. DCA confirmed that the nomogram model was clinically useful when the incidence of PVT in patients was 5%-60%. Conclusion: We have established a high-performance nomogram for predicting the risk of PVT in patients undergoing PC surgery. This will assist clinical doctors in identifying individuals at high risk of PVT and taking appropriate preventive measures.

Venous thromboembolism in patients undergoing distal cholangiocarcinoma surgery: Prevalence, risk factors, and outcomes.

BACKGROUND: To investigate venous thromboembolism (VTE) in patients undergoing distal cholangiocarcinoma (dCCA) surgery, we performed a single-center study to assess its prevalence, risk factors, prognosis. METHOD: We studied a total of 177 patients undergoing dCCA surgery from January 2017 to April 2022. Demographic, clinical data, laboratory data (including lower extremity ultrasound findings), and outcome variables were obtained, and compared between VTE and non-VTE groups. RESULTS: Of the 177 patients undergoing dCCA surgery (aged 65.2 ± 9.6 years; 108 (61.0%) male), 64 patients developed VTE after surgery. Logistic multivariate analysis showed that, age, operation procedure, TNM stage, ventilator duration and preoperative D-dimer were independent risk factors. Based on these factors, we constructed the nomogram to predict VTE after dCCA for the first time. The areas under the receiver operating curve (ROC) of the nomogram were 0.80 (95% CI: 0.72-0.88) and 0.79 (95% CI: 0.73-0.89) in the training and validation groups, respectively. Patients developed VTE had a worse prognosis by Kaplan-Meier curve analysis (p = 0.001). CONCLUSION: The prevalence of VTE is high and is associated with adverse outcomes in patients undergoing dCCA surgery. We developed a nomogram assessing VTE risk, which may help clinicians to screen out people at high risk for VTE and to undertake rational preventive measures.

Prognostic Value for Perioperative Serum Total Cholesterol Level on Postoperative Long-Term Prognosis of Pancreatic Cancer: A Retrospective Clinical Study.

Cholesterol correlates with occurrence and progression of pancreatic cancer and has predictive value for postoperative prognosis in various cancers. Our study intended to reveal the relationship between perioperative serum total cholesterol (TC) level and postoperative prognosis of pancreatic cancer. We retrospectively analyzed the data of pancreatic cancer patients who underwent surgical treatment at our hospital from January 2015 to December 2021. ROC curves between serum TC level at each time point and 1-year survival rate were drawn, from which study object and optimal cutoff value was determined. Patients were divided into low and high-TC groups, and perioperative data and prognosis were compared. Risk factors for poor postoperative prognosis were identified by univariate and multivariate analysis. Overall survival rates at postoperative 1, 2 and 3 years in the low and high-TC groups were 52.9%, 29.4%, and 15.6% and 80.4%, 47.2%, and 33.8% (p = 0.005), respectively. Multivariate analysis confirmed tumor differentiation degree (RR = 2.054, 95% CI: 1.396-3.025), pTNM stage (RR = 1.595, 95% CI: 1.020-2.494), lymph node metastasis (RR = 1.693, 95% CI: 1.127-2.544), and postoperative 4-week serum TC level (RR = 0.663, 95% CI: 0.466-0.944) as independent risk factors for prognosis of pancreatic cancer. We conclude that postoperative 4-week serum TC level has certain predictive value for long-term postoperative prognosis of pancreatic cancer.

Protective Effects of Different Hypothermal Preservation Solutions on Structure and Function of Isolated Rat Arteries.

OBJECTIVE: With the increasing application of vascular reconstruction in surgical procedures, allogeneic vessels are becoming more popular in clinical practice due to their abundant sources, precise diameter matching, improved histocompatibility, and higher long-term patency rate. This study aimed to investigate the protective effect of various preservation solutions on the function and structure of the isolated rat abdominal aorta preserved under hypothermal conditions. METHODS: The study utilized a total of 150 Sprague-Dawley (SD) rats, with 144 rats allocated to the experimental groups and 6 rats allocated to the control groups. The abdominal aorta of the rats was chosen as the subject of our research. The aorta in the experimental groups were randomly assigned to 4 groups: University of Wisconsin (UW) solution group, histidine-tryptophan-ketoglutarate (HTK) solution group, normal saline (NS) group, and sodium lactate Ringer's solution (RS) group. Samples were subjected to examination after preservation periods of 1 day, 3 days, 5 days, 7 days, 14 days, 30 days, and 90 days. Evaluation of vascular physiological function involved detecting and assessing vasoconstriction ability and measuring cell viability through the MTT test. Evaluation of the vascular wall structure involved tension tolerance tests and pathological staining. RESULTS: The pathogen-positive rate in the HTK group and NS group at 1 month was 16.7%. Regarding the vascular skeleton structure, both the UW group and HTK group exhibited intact structures after 2 weeks of preservation, with slightly edematous collagen and elastic fibers, which was significantly better than that of the NS group and RS group. In terms of cell activity and contractile function, all preservation groups showed similar effects within 2 weeks. However, after 2 weeks, the UW group showed the most favorable preservation effect (P<0.05). In terms of vascular tension, different groups exhibited similar effects within 1 week. However, after 2 weeks, the UW group showed the best preservation effect (P<0.05). CONCLUSION: All 4 types of preservation solution had a preservation effect on the structure and function of isolated blood vessels during short-term hypothermal preservation. However, after 2-week preservation, the UW solution was found to be the most suitable solution for the preservation of blood vessels.

Application of cholecystic duct plasty in the prevention of biliary complications following orthotopic liver transplantation.

Background: The purpose was aimed to evaluate the safety and effectiveness of cholecystic duct plasty (CDP) and biliary reconstruction techniques preventing biliary complications following orthotopic liver transplantation (OLT) first proposed by our center. Methods: 127 enrolled patients who underwent LT in our center from January 2015 to December 2019 were analyzed retrospectively. According to the mode of biliary tract reconstruction, patients were divided into CDP group (Group 1, n = 53) and control group (Group 2, n = 74). The differences of perioperative general data, biliary complications and long-term prognosis between two groups were compared and analyzed. Results: All patients completed the operation successfully, the incidence of perioperative complications was 22.8%. There was no significant difference in perioperative general data and complications between the two groups. Follow-up ended in June 2020, with a median follow-up period of 31 months. During the follow-up period, biliary complications occurred in 26 patients, with an overall incidence of 20.5%. The overall incidence of biliary complications and anastomotic stenosis in Group 1 was lower than that in Group 2 (P < 0.05). There was no significant difference in overall prognosis between the two groups (P = 0.274), however, the cumulative incidence of biliary complications in Group 1 was lower than that in Group 2 (P = 0.035). Conclusion: Reconstruction of common bile duct by CDP represents considerable safety and practicability, particularly for patients with small diameter of common bile duct or wide discrepancy of bile duct size between donor and recipient.

Corrigendum: Application of cholecystic duct plasty in the prevention of biliary complications following orthotopic liver transplantation.

[This corrects the article DOI: 10.3389/fsurg.2023.1087327.].

Clinical Value of Mean Platelet Volume to Platelet Ratio (MPR) in Distinguishing Mass-Forming Chronic Pancreatitis and Pancreatic Cancer.

BACKGROUND: Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC. METHODS: We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC (n = 383) and MFCP groups (n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings. RESULTS: The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively (p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively (p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively. CONCLUSION: MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.

Bioengineering a glucose oxidase nanosensor for near-infrared continuous glucose monitoring.

Single-walled carbon nanotubes (SWCNTs) emit photostable near-infrared (NIR) fluorescence that is conducive for optical glucose monitoring. Such SWCNT-based optical sensors often require the immobilization of proteins that can confer glucose selectivity and reactivity. In this work, we immobilize a glucose-reactive enzyme, glucose oxidase (GOx), onto SWCNTs using a N-(1-pyrenyl)maleimide (PM) crosslinker via thiol bioconjugation of engineered cysteine residues. We compare the conjugation of several glucose oxidase variants containing rationally-engineered cysteines and identify a D70C variant that shows effective bioconjugation. The bioconjugation was characterized through both absorption and fluorescence spectroscopy. Furthermore, we demonstrate an application for continuous glucose monitoring in the NIR-II optical region using the bioconjugated reaction solution, which shows a reversible response to physiological concentrations of glucose. Finally, we develop a miniaturized NIR-II reader to be used for cell cultures that require continuous glucose monitoring.

Prognostic Value of Neoadjuvant Chemotherapy in Patients with Borderline Resectable Pancreatic Carcinoma Followed by Pancreatectomy with Portal Vein Resection and Reconstruction with Venous Allograft.

BACKGROUND: Neo-adjuvant chemotherapy (NAC) represents one of the current research hotspots in the field of pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate the prognostic value of NAC in patients with borderline resectable pancreatic cancer (BRPC) followed by pancreatectomy with portal vein (PV) resection and reconstruction with venous allograft (VAG). METHODS: Medical records of patients with BPRC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG between April 2013 and March 2021 were analyzed retrospectively. Outcomes of patients with and without NAC (NAC, Group 1 vs. non-NAC, Group 2) were compared with focus on R0 resection rates, morbidity, and survival. RESULTS: Of the 77 patients with pancreatectomy, PV resection and reconstruction with VAG were identified. Overall survival (OS) rates of 0.5-, 1-, and 2-year were 80.5%, 59.7%, and 31.2%, respectively (median survival time, MST, 14 months). Of these, 24 patients (Group 1) underwent operation following received NAC, and the remaining 53 patients did not (Group 2). The R0 resection rate of vascular margin was 100% vs. 84.9% (p = 0.04), respectively. Morbidity of post-operative pancreatic fistula (POPF) was 0% vs. 17.8% (p = 0.07), respectively. The OS of 0.5-, 1- and 2-year and MST of 2 groups were 83.3%, 66.7%, 41.7%, 16 months, and 79.2%, 55.6%, 26.4%, 13 months, respectively. Multivariate analysis revealed that carbohydrate antigen 19-9 (CA19-9) serum level and postoperative chemotherapy were independent prognostic factors in patients with BRPC after surgery. CONCLUSION: NAC might improve the R0 resection rate and POPF in patients with BRPC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG. Survival benefit exists in patients with BRPC who received NAC before pancreatectomy. Postoperative chemotherapy also had a favorable effect on OS of BRPC patients. Elevated CA 19-9 serum level is associated with poor prognosis, even after NAC-combining operation.

Clinical value of extended lymphadenectomy in radical surgery for pancreatic head carcinoma at different T stages.

BACKGROUND: As the lymph-node metastasis rate and sites vary among pancreatic head carcinomas (PHCs) of different T stages, selective extended lymphadenectomy (ELD) performance may improve the prognosis of patients with PHC. AIM: To investigate the effect of ELD on the long-term prognosis of patients with PHC of different T stages. METHODS: We analyzed data from 216 patients with PHC who underwent surgery at our hospital between January 2011 and December 2021. The patients were divided into extended and standard lymphadenectomy (SLD) groups according to extent of lymphadenectomy and into T1, T2, and T3 groups according to the 8th edition of the American Joint Committee on Cancer's staging system. Perioperative data and prognoses were compared among groups. Risk factors associated with prognoses were identified through univariate and multivariate analyses. RESULTS: The 1-, 2- and 3-year overall survival (OS) rates in the extended and SLD groups were 69.0%, 39.5%, and 26.8% and 55.1%, 32.6%, and 22.1%, respectively (P = 0.073). The 1-, 2- and 3-year disease-free survival rates in the extended and SLD groups of patients with stage-T3 PHC were 50.3%, 25.1%, and 15.1% and 22.1%, 1.7%, and 0%, respectively (P = 0.025); the corresponding OS rates were 65.3%, 38.1%, and 21.8% and 36.1%, 7.5%, and 0%, respectively (P = 0.073). Multivariate analysis indicated that portal vein invasion and lymphadenectomy extent were risk factors for prognosis in patients with stage-T3 PHC. CONCLUSION: ELD may improve the prognosis of patients with stage-T3 PHC and may be of benefit if performed selectively.

CA19-9 Level to Serum γ-Glutamyltransferase as a Potential Prognostic Biomarker in Patients with Pancreatic Head Carcinoma.

BACKGROUND: The aim of this study was to reduce the influence of biliary obstruction on carbohydrate antigen 19-9 level (CA19-9) by introducing the CA19-9 level to serum γ-glutamyltransferase (GGT) ratio as an indicator, and ultimately to reveal the correlation between CA19-9/GGT and the prognosis of patients with pancreatic head carcinoma (PHC). METHODS: A total of 339 enrolled patients who underwent pancreatoduodenectomy for PHC in Beijing ChaoYang Hospital from January 2010 to December 2019 were analyzed retrospectively. The optimal cut-off value, according to which patients were divided into a low-ratio group (Group 1, n=179) and a high-ratio group (Group 2, n=160), was determined by the ROC curve obtained from preoperative CA19-9/GGT and 1-year survival. Through univariate and multivariate analyses, risk factors for postoperative tumor recurrence and long-term survival were screened out among PHC patients. RESULTS: The best cut-off value of CA19-9/GGT was 2.07 (area under the curve=0.567, 95% CI 0.498-0.636). Compared with Group 2, Group 1 had lower CA19-9, and higher GGT, total bilirubin (TB) and lymph-node metastasis rate (P<0.05). The 1-, 2- and 3-year disease-free survival rates of patients in Groups 1 and 2 were 68.2%, 42.5% and 28.2%, and 42.2%, 19.3% and 18.3%, respectively (P=0.000), and the 1-, 2- and 3-year overall survival rates were 79.1%, 50.7% and 29.1%, and 56.7%, 22.2% and 17.2%, respectively (P=0.000). Multivariate analysis showed that CA19-9/GGT, portal system invasion and lymph-node metastasis were independent risk factors for postoperative tumor recurrence and long-term survival among patients with PHC. CONCLUSION: Compared with CA19-9 level alone, CA19-9/GGT plays a more precise role in the evaluation of postoperative tumor recurrence and the long-term prognosis of PHC patients. The lower the ratio, the better the long-term prognosis. The CA19-9/GGT ratio may prove to be a useful biomarker for identifying PHC patients at high risk of early recurrence and unfavorable prognosis.

Therapeutic Effect of Combining Anisodamine With Neostigmine on Local Scar Formation Following Roux-en-Y Choledochojejunostomy in a Novel Rat Model.

Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model. Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 µg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study. Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1ß) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-ß1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats' bile duct wall and less local scar formation at anastomotic stoma compared to the control group. Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure.

Self-Assembling Glycopeptide Conjugate as a Versatile Platform for Mimicking Complex Polysaccharides.

Polysaccharides are a class of carbohydrates that play pivotal roles in living systems such as being chemical messengers in many vital biological pathways. However, the complexity and heterogeneity of these natural structures have posed daunting challenges on their production, characterization, evaluation, and applications. While there have been various types of synthetic skeletons that could mimic some biological aspects of polysaccharides, a safer and more easily accessed system is still desired to avoid the unnatural components and difficulties in modifying the structures. In this work, conveniently accessible self-assembling glycopeptide conjugates are developed, where the natural O-glycosidic linkages and phosphoryl modifications assist the self-assembly and concurrently reduce the risk of toxicity. The generated nanoparticles in aqueous solution offer a multivalent display of structurally controllable carbohydrates as mimics of polysaccharides, among which a mannosylated version exhibits immunostimulatory effects in both cellular assays and vaccination of mice. The obtained results demonstrate the potential of this glycopeptide conjugate-derived platform in exploiting the intriguing properties of carbohydrates in a more structurally maneuverable fashion.