Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Exploring the Risk Factors for Deep Vein Thrombosis after Percutaneous Nephrolithotomy.

BACKGROUND: Deep vein thrombosis (DVT), a frequent complication following percutaneous nephrolithotomy (PCNL), may lead to severe conditions like pulmonary embolism. Current knowledge on postoperative DVT risk factors is, however, limited. The aim of our study was to investigate the risk of DVT after PCNL. METHODS: A retrospective study was conducted on patients who underwent PCNL from March 2020 to March 2023 at our institution. Patient demographics and clinical data, including, DVT-specific information, preoperative labs, and surgical details, was evaluated. RESULTS: One hundred patients were included. Thirty-two (20 males, 12 females, mean age 52.5 ± 7.4 years) developed lower limb DVT post-surgery, while the remaining 68 (48 males, 20 females, mean age 51.1 ± 5.5 years) had no DVT symptoms. Analysis revealed significant correlations between hyperlipidemia, operating time, postoperative bed rest duration, D-dimer level on the first day after surgery, Caprini risk assessment model (RAM) score, and DVT risk. D-dimer on the first day after percutaneous nephrolithotomy, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL. Sex, age, hypertension status, diabetes status and smoking and drinking habits were not significantly associated with DVT risk. CONCLUSIONS: D-dimer on the first day after PCNL, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL.

Total endoscopic sublay mesh repair for umbilical hernias.

ABSTRACT: Umbilical hernias constitute some of the most common surgical diseases addressed by surgeons. Endoscopic techniques have become standard of care together with the conventional open techniques for the treatment of umbilical hernias. Several different approaches were described to achieve laparoscopic sublay repair.We prospectively collected and reviewed the medical records of 10 patients with umbilical hernias underwent total endoscopic sublay repair (TES) at our institution from November 2017 to November 2019. All operations were performed by a same surgical team. The demographics, intraoperative details, and postoperative complications were evaluated.All TES procedures were successfully performed without conversion to an open operation. No intraoperative morbidity was encountered. The average operative time was 109.5 minutes (range, 80-140 minutes). All the patients resumed an oral diet within 6 hours after the intervention. The mean time to ambulation was 7.5 hours (range, 4-14 hours), and mean postoperative hospital stay was 2.2 day (range, 1-4 days). One patient developed postoperative seroma. No wound complications, chronic pain, or recurrence were registered during the follow-up.Initial experiences with this technique show that the TES is a safe, and effective procedure for the treatment of umbilical hernias.

Role of Lipids and Apolipoproteins in Predicting the Prognosis of Hepatocellular Carcinoma After Resection.

PURPOSE: To further clarify the association between abnormal levels of serum lipid components as the main features of dyslipidaemia and hepatocellular carcinoma, which remains unclear. PATIENTS AND METHODS: We examined the serum level of lipids and apolipoproteins pattern in 471 patients undergoing curative resection for HCC, 193 patients with chronic liver disease, and 104 patients with benign liver diseases. We performed uni- and multivariate analyses to evaluate the predictive roles of lipids and apolipoproteins for recurrence and survival of HCC in a training cohort of 242 patients and then validated in a cohort of 229 patients. RESULTS: The majority circulating lipid and apolipoprotein levels such as ApoA1, HDL, and LDL in chronic liver disease and HCC were slightly significantly decreased as compared to those in benign lesion. But no significant differential expression patterns of lipids and apolipoproteins were observed between chronic liver hepatitis and HCC. Multivariable analysis identified ApoA1 as a key parameter related to recurrence and survival in both training and validation cohorts. Moreover, we further demonstrated that low ApoA1 was an independent prognostic factor of poor early recurrence in two cohorts. CONCLUSION: Although the alterations of circulating lipids and apolipoproteins were observed in HCC, none of lipids or apolipoproteins could serve as a diagnostic marker. Serum ApoA1 merits consideration as a novel prognostic marker for patients with HCC undergoing surgery since it predicts early recurrence and survival, especially for early stage patients and may improve the prognostic stratification of patients for clinical management and promote HCC clinic outcomes.

Trans-umbilical single-incision laparoscopic trans-abdominal pre-peritoneal hernioplasty of inguinal hernia by self-made glove port.

Laparoscopic inguinal herniorrhaphy has been well established for the management of primary and recurrent inguinal hernias. Single-incision laparoscopic surgery (SILS) has now been accepted as a less invasive alternative to conventional laparoscopic surgery. However, commercially available access devices for SILS had disadvantages such as rigidness and crowding. This series aimed to analyze the feasibility and safety of single-incision laparoscopic trans-abdominal pre-peritoneal hernioplasty (SILS-TAPP) by applying our self-made device for managing inguinal hernia.We collected and reviewed the medical records of patients who received SILS-TAPP using a self-made glove-port device between January 2014 and January 2016. All operations were performed by the same surgical team. The demographics and intra- and perioperative outcomes were evaluated.SILS-TAPP was successfully performed in 105 patients (131 inguinal hernia repairs). No major intra- and postoperative morbidities were encountered, and no conversion to a conventional 3-port approach or open surgery was required. The mean operative time was 73.5 min and the mean postoperative hospital stay was 2.1 days. Three minor short-term complications were noted, which were resolved without surgical intervention. One recurrence was diagnosed during follow-up and treated using a second TAPP procedure.SILS-TAPP was shown to be a feasible, safe procedure in patients with an inguinal hernia. A simple self-made glove-port device was proven as a practical method of SILS-TAPP.

Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center propensity score matching study.

Laparoscopic distal pancreatectomy (LDP) for benign and low-grade malignant pancreatic diseases has been increasingly utilized. However, the use of LDP for pancreatic ductal adenocarcinoma (PDAC) remains controversial and has not been widely accepted. In this study, the outcomes of LDP versus conventional open distal pancreatectomy (ODP) for left-sided PDAC were examined. A retrospective review of patients who underwent LDP or ODP for left-sided PDAC between January 2010 and January 2019 was conducted. One-to-one propensity score matching (PSM) was used to minimize selection biases by balancing factors including age, sex, ASA grade, tumor size, and combined resection. Demographic data, their pathological and short-term clinical parameters, and long-term oncological outcomes were compared between the LDP and ODP groups. A total of 197 patients with PDAC were enrolled. There were 115 (58.4%) patients in the LDP group and 82 (41.6%) patients in the ODP group. After 1:1 PSM, 66 well-matched patients in each group were evaluated. The LDP group had lesser blood loss (195 vs. 210 mL, p < 0.01), shorter operative time (193.6 vs. 217.5 min; p = 0.02), and shorter hospital stay (12 vs. 15 days, p < 0.01), whereas the overall complication rates were comparable between groups (10.6% vs.16.7%, p = 0.31). There were no significant differences between the LDP and ODP groups regarding 3-year recurrence-free or overall survival rate (p = 0.89 and p = 0.33, respectively). LDP in the treatment of left-sided PDAC is a technically safe, feasible and favorable approach in short-term surgical outcomes. Moreover, patients undergoing LDP than ODP for PDAC had comparable oncological metrics and similar middle-term survival rate.

Recommendations for the Development and Validation of Immunogenicity Assays in Support of Biosimilar Programs.

For biosimilar drug development programs, it is essential to demonstrate that there are no clinically significant differences between the proposed biosimilar therapeutic (biosimilar) and its reference product (originator). Based on a stepwise comprehensive comparability exercise, the biosimilar must demonstrate similarity to the originator in physicochemical characteristics, biological activity, pharmacokinetics, efficacy, and safety, including immunogenicity. The goal of the immunogenicity assessment is to evaluate potential differences between the proposed biosimilar product and the originator product in the incidence and severity of human immune responses. Establishing that there are no clinically meaningful differences in the immune response between the products is a key element in the demonstration of biosimilarity. An issue of practical, regulatory, and financial importance is to establish whether a two-assay (based on the biosimilar and originator respectively) or a one-assay approach (based on the biosimilar) is optimal for the comparative immunogenicity assessment. This paper recommends the use of a single, biosimilar-based assay for assessing immunogenic similarity in support of biosimilar drug development. The development and validation of an ADA assay used for a biosimilar program should include all the assessments recommended for an innovator program (10-16, 29). In addition, specific parameters also need to be evaluated, to gain confidence that the assay can detect antibodies against both the biosimilar and the originator. Specifically, the biosimilar and the originator should be compared in antigenic equivalence, to assess the ability of the biosimilar and the originator to bind in a similar manner to the positive control(s), as well as in the confirmatory assay and drug tolerance experiments. Practical guidance for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity of a biosimilar in comparison to the originator, using the one-assay approach, are described herein.

Repeated lumps and infections: A case report on breast augmentation complications.

BACKGROUND: Polyacrylamide hydrogel (PAAG) injections were once common in breast augmentation and have been prohibited for augmentation mammaplasty in China since a large number of patients who underwent breast augmentation with PAAG injections have continued to seek medical advice as a result of related complications. Among all these complications, distant migration is relatively rare. CASE SUMMARY: A 49-year-old female presented at the hospital with a one-year history of a vulvar lump. The sonography of the lump showed several subcutaneous fluid-filled regions from the left vulva to the pubic symphysis, which suggested possible fat liquefaction. An enhanced magnetic resonance imaging (MRI) revealed a cystic area, which was considered a benign lesion. Intraoperative observations showed that the mass did not have an obvious capsule, the subcutaneous tissue presented as a cavity, and some yellow material came out of this cavity. A culture of the drainage did not show bacterial contamination. Histopathology revealed a foreign body granuloma. After resection and closed drainage, lumps were successively observed in the left lower abdomen and the bilateral hypochondriac region with infections. Sonography found that the hypoechoic areas in the bilateral hypochondriac region seemed continuous with deep in the breasts. The patient reported that she had undergone surgery with PAAG injections 20 years ago after she was repeatedly asked about her past history. Finally, a diagnosis of distant migration of PAAG was made. CONCLUSION: PAAG gel can migrate after long periods of time. A diagnosis should not be limited to the area where the symptom develops.

An imbalance between stellate cells and γδT cells contributes to hepatocellular carcinoma aggressiveness and recurrence.

PURPOSE: The diagnostic potential of hepatic stellate cells (HSCs) and γδT cells for patients with hepatocellular carcinoma (HCC) and their synergistic contributions to the prognosis of these patients have not yet been investigated. The aim of this study was to elucidate the prognostic value of these cells in HCC. METHODS: The prognostic significance of the ratio of HSCs to γδT cells (SGR) was assessed in a total of 339 HCC patients undergoing resection. The correlation between the circulating tumor cell (CTC) level and SGR in 71 HCC patients was determined using the CellSearch system. In vitro experiments were performed to validate the synergistic effects of HSCs and γδT cells on hepatoma cells. RESULTS: Peritumoral SGR was closely associated with overall survival (OS) and recurrence-free survival (RFS) of HCC patients after resection. In the testing cohort, two nomograms incorporating the SGR were constructed for the prediction of OS and RFS. The predictive accuracy of the two nomograms was verified by the validation cohort. CTC levels were positively correlated with SGR (r = 0.479, p < 0.001). Among the patients with CTCs > 2/7.5 ml, those with a high SGR exhibited higher early recurrence rates than those with a low SGR. In vitro experiments revealed that the secretion of INF-γ, IL-17, and TNF-α from γδT cells was increased after culture with HSC-conditioned medium. In addition, γδT cells cultured with HSC-conditioned medium decreased the proliferative and invasive abilities of hepatoma cells. CONCLUSIONS: The peritumoral SGR is related to aggressive tumor behavior and has a powerful predictive value in HCC. Early recurrence in patients with a high peritumoral SGR might be associated with high CTC levels.

Inflammation-nutrition score predicts prognosis of patients with resectable hepatocellular carcinoma.

BACKGROUND: Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC). METHODS: Data were collected retrospectively from 674 HCC patients who underwent curative resection. The correlation between INS (inflammation-nutrition score), BCLC (Barcelona Clinic Liver Cancer) stage and inflammatory indices and overall survival (OS) and disease free survival (DFS) was examined. RESULTS: An elevated INS was associated with both tumor and host clinical characteristics. The combination of INS and BCLC stage stratifies OS and DFS from 80% and 65% (INS = 0, stage A) to 0% (INS = 2, stage C). Univariate and multivariate analyses revealed that the INS was an independent predictor for OS and DFS, and was superior to inflammation-based scores. In addition, INS was demonstrated to be a prognostic factor for patients with early stage and had a higher AUC value in comparison with inflammation scores. CONCLUSION: This study demonstrates that the INS is an independent marker of poor prognosis in patients with resectable HCC, especially for those with early stage, and it provides complimentary prognostic information to BCLC stage, and may aid in treatment strategy.

Differences in treatment outcomes between ultrasound-guided percutaneous microwave ablation and endoscopic thyroidectomy for patients with papillary thyroid microcarcinoma: Protocol for a systematic review and meta-analysis.

BACKGROUND: The differences in treatment outcomes between ultrasound (US)-guided percutaneous microwave ablation (PMWA) and endoscopic thyroidectomy for patients with papillary thyroid microcarcinoma (PTMC) remains unknown. METHODS: An electronic search will be performed for randomized controlled trials or observational studies that reported recurrence and mortality rates in PTMC patients with US-guided PMWA or endoscopic thyroidectomy. Hazard ratios with their 95% confidence intervals will be calculated using fixed- or random-effects models according to heterogeneity. RESULTS: This study will present the differences in treatment outcomes between US-guided PMWA and endoscopic thyroidectomy for patients with PTMC by pooling the results of individual studies. CONCLUSION: The results of this study would provide vigorous evidence in this issue and offer the guidance to both clinical decision-making and future research. ETHICS AND DISSEMINATION: Ethical approval is not applicable for this study. PROSPERO REGISTRATION NUMBER: CRD42018112320.

Modified laparoscopic Sugarbaker repair of parastomal hernia with a three-point anchoring technique.

AIM: To retrospectively evaluate the safety and feasibility of a new modified laparoscopic Sugarbaker repair in patients with parastomal hernias. METHODS: A retrospective study was performed to analyze eight patients who underwent parastomal hernia repair between June 2016 and January 2018. All of these patients received modified laparoscopic Sugarbaker hernia repair treatment. This modified technique included an innovative three-point anchoring and complete suturing technique to fix the mesh. All procedures were performed by a skilled hernia surgeon. Demographic data and perioperative outcomes were collected to evaluate the safety and efficacy of this modified technique. RESULTS: Of these eight patients, two had concomitant incisional hernias. All the hernias were repaired by the modified laparoscopic Sugarbaker technique with no conversion to laparotomy. Three patients had in-situ reconstruction of intestinal stoma. The median mesh size was 300 cm2, and the mean operative time was 205.6 min. The mean postoperative hospitalization time was 10.4 d, with a median pain score of 1 (visual analog scale method) at postoperative day 1. Two patients developed postoperative complications. One patient had a pocket of effusion surrounding the biologic mesh, and one patient experienced an infection around the reconstructed stoma. Both patients recovered after conservative management. There was no recurrence during the follow-up period (6-22 mo, average 13 mo). CONCLUSION: The modified laparoscopic Sugarbaker repair could fix the mesh reliably with mild postoperative pain and a low recurrence rate. The technique is safe and feasible for parastomal hernias.

High expression of CD39 in gastric cancer reduces patient outcome following radical resection.

Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also known as cluster of differentiation (CD)39, is the rate-limiting enzyme in the generation of immunosuppressive adenosine and is important in tumor progression. The present study evaluated the expression of CD39+ and CD39+ forkhead box P3 (FoxP3)+ regulatory T (Treg) cells in gastric cancer (GC), and determined their prognostic roles in patients with GC following radical resection. It was observed that CD39 was expressed at significantly higher rates in tumor tissues as compared with paired peritumoral tissues. Overexpression of tumor CD39 was correlated with overall survival (OS). Furthermore, CD39 expression in GC tissues exhibited a prognostic role in OS. The CD39+ FoxP3+/FoxP3+ ratio in tumor tissues was higher than that in paired peritumoral tissues, and CD39+ FoxP3+ Treg cells were a better prognostic indicator than FoxP3+ Treg cells for OS. Collectively, our study indicates that overexpression of CD39 in GC is a predictor of poor outcome for GC patients following radical resection. CD39+ FoxP3+ Treg cells are a potential target for cancer immunotherapy.

Overexpression of CD39 in hepatocellular carcinoma is an independent indicator of poor outcome after radical resection.

Nucleoside triphosphate diphosphohydrolase-1 (ENTPD1/CD39) is the rate-limiting enzyme in a cascade leading to the generation of immunosuppressive adenosine and plays an important role in tumor progression. This study aimed to evaluate the expression of CD39 and CD39Foxp3 regulatory T cells (Tregs) and to determine their prognostic role in patients with hepatocellular carcinoma (HCC) after radical resection.Immunohistochemistry (IHC) and double IHC were used to analyze CD39 expression or the expression of CD39 and Foxp3 in a cohort of 324 HCC patients who underwent curative resection. The quantification of CD39 expression levels was determined using a computerized image analysis system and was evaluated by mean optical density (MOD), which corresponded to the positive staining intensity of CD39. The number of positive Foxp3 cells and both CD39 and Foxp3 positive cells in each 1-mm-diameter cylinder were counted under high-power magnification (×400). The "minimum P value" approach was used to obtain the optimal cutoff value for the best separation between groups of patients in relation to time to recurrence (TTR) or overall survival (OS). The expression of CD39 in HCC cell lines with stepwise metastatic potential and in human umbilical vein endothelial cells was determined by reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence. The SPSS 17.0 statistical package was used for statistics.CD39 was principally expressed on vascular endothelial cells, macrophagocytes, Tregs, and tumor cells in HCC. Compared with paired peritumoral tissues, tumoral tissues had a significantly higher expression level of CD39 (P < 0.0001). Overexpression of tumoral CD39 was related to increased tumor recurrence and shortened overall survival. Furthermore, the expression level of peritumoral CD39 showed a prognostic role in TTR and OS. Double IHC showed that tumoral tissues had significantly higher Foxp3Tregs and CD39Foxp3Tregs count per 1 mm core (14.1659 vs 4.9877, P = 0.001; 11.5254 vs 3.3930, P < 0.001) and a higher CD39Foxp3/Foxp3 ratio compared with paired peritumoral tissues. CD39Foxp3Tregs were a better prognosticator than CD39Tregs for TTR.Overexpression of CD39 protein in HCC was an independent predictor of poor outcome after radical resection. The CD39Foxp3Tregs count added prognostic power to Foxp3Tregs, providing a potential target for tumor immunotherapy.

PEG-based hydrogels prepared by catalyst-free thiol-yne addition and their post-antibacterial modification.

PEG-based hydrogels possess tissue-like mechanical elasticity, solute permeability, cytocompatibility and biocompatibility. In this work, PEG-based hydrogels were prepared via nucleophilic thiol-yne addition between a 4-arm PEG functionalized with thiols (PEG10k-4-SH) and an electron-deficient alkyne (PEG10k-4-PP). The as-fabricated hydrogels still possess residual functionalities, enabling a second nucleophilic thiol-yne addition on the gel matrix. A thiol-containing fluorescent dye was conjugated with the electron-deficient alkyne appended hydrogels. A thiol-containing antimicrobial peptide (AMP-SH) was also embedded into the gel matrix via nucleophilic thiol-yne addition. The inhibition of bacterial growth in suspensions and contaminated substrate surfaces by the AMP-embedded hydrogels was studied. The cytotoxicity of unmodified and AMP-embedded PEG-based hydrogels against 3T3 fibroblasts was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) viability assay.

Biomimetic anchors applied to the host-guest antifouling functionalization of titanium substrates.

A biomimetic strategy was developed for the construction of antifouling titanium oxide (Ti(oxide)) surfaces based on host-guest interactions. Two catecholic derivatives, dopamine 4-(phenylazo)benzamide (AZODopa) and dopamine 1-adamantanecarboxamide (AdaDopa) were synthesized and immobilized onto the Ti(oxide) surfaces. The guest molecules-anchored Ti(oxide) surfaces were further functionalized with zwitterionic heptakis[6-deoxy-6-(N-3-sulfopropyl-N,N-dimethylammonium ethyl sulfanyl)]-ß-cyclodextrin (SBCD) and hydrophilic ß-CD polymer (CDP). The surface elemental compositions and hydrophobic/hydrophilic properties of the Ti(oxide) surfaces before and after modification were characterized by X-ray photoelectron spectroscopy (XPS) and static water contact angle measurements, respectively. The antifouling properties of the modified Ti(oxide) surfaces were evaluated by the protein adsorption and bacterial adhesion assays. The zwitterionic SBCD- and hydrophilic CDP-functionalized Ti(oxide) surfaces can reduce the adsorption of bovine plasma fibrinogen and adhesion of Escherichia coli, as compared to the pristine and guest molecules-anchored Ti(oxide) surfaces.

Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.

BACKGROUND: Aberrant expression of interleukin-35 (IL-35) has been implicated in dampening antitumour immunity. The aim of this study was to explore the prognostic significance of IL-35 expression in patients with hepatocellular carcinoma (HCC) following curative resection. Furthermore, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy. METHODS: Immunohistochemistry was applied to explore IL-35 expression as well as CD39(+)Foxp3(+) and Foxp3(+) regulatory T cell (Treg) infiltration in tissue microarrays in primary cohort comprising 210 randomly selected HCC patients who underwent curative resection. The results were further verified in an independent validation cohort of 138 HCC patients. RESULTS: Patients with higher expression of IL-35 are more likely to suffer postoperative recurrence. Interleukin-35 was also identified as an independent prognostic factor for recurrence free survival in multivariate analysis. No correlation was detected between IL-35 expression and Foxp3(+) Treg infiltration, whereas significant positive correlation was found between IL-35 expression and CD39(+)Foxp3(+) Treg infiltration. In addition, CD39(+)Foxp3(+) Treg infiltration was also an independent predictor for postoperative recurrence. The nomogram comprising tumour size, tumour vascular invasion, IL-35 and CD39(+)Foxp3(+) Tregs had better predictive accuracy when compared with BCLC stage for RFS. These results were further validated in the validation cohort. CONCLUSIONS: Our data suggest for the first time that IL-35 expression correlates with HCC aggressiveness and emerged as a novel independent prognostic factor for recurrence, thus conferring the rationale to develop a novel therapy of targeting IL-35. Furthermore, IL-35 should be incorporated into nomogram to generate a more accurate predictive model.

A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection: A STROBE-Compliant Article.

As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature.In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone.IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy.

Conjugation of Lectin to Poly(ε-caprolactone)-block-glycopolymer Micelles for In Vitro Intravesical Drug Delivery.

Amphiphilic poly(ε-caprolactone)-block-poly[2-(α-d-mannopyranosyloxy) ethyl acrylamide] (PCL-b-PManEA) block copolymers were synthesized via a combination of ring-opening polymerization (ROP), reversible addition-fragmentation chain transfer (RAFT) polymerization and reactive ester-amine reaction. The PCL-b-PManEA block copolymers can self-assemble into micelles and encapsulate anticancer drug doxorubicin (DOX). To enhance mucoadhesive property of the resulting DOX-loaded PCL-b-PManEA micelles, Concanavalin A (ConA) lectin was further conjugated with the micelles. Turbidimetric assay using mucin shows that the DOX-loaded PCL-b-PManEA@ConA micelles are mucoadhesive. DOX release from the DOX-loaded PCL-b-PManEA@ConA micelles in artificial urine at 37 °C exhibits an initial burst release, followed by a sustained and slow release over three days. Confocal laser scanning microscope (CLSM) images indicate that the DOX-loaded PCL-b-PManEA@ConA micelles can be effectively internalized by UMUC3 human urothelial carcinoma cells. The DOX-loaded PCL-b-PManEA@ConA micelles exhibit significant cytotoxicity to these cells.