Comparison of prognosis and postoperative morbidities between standard pancreaticoduodenectomy and the TRIANGLE technique for resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocarcinoma (PDAC), although tumor recurrence, especially locally, still inhibits the treatment efficacy. The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC. However, there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC. AIM: To compare the prognosis and postoperative morbidities between standard pancreaticoduodenectomy (PD) and the TRIANGLE technique for resectable PDAC. METHODS: Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study. All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure. Baseline characteristics, surgical data, and postoperative morbidities were recorded. All of the patients were followed up, and the date and location of tumor recurrence, and death were recorded. The Kaplan-Meier method and log-rank test were used for the survival analysis. RESULTS: There were 93 patients included in the study and 37 underwent the TRIANGLE technique. Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group [440 (410-480) min vs 320 (265-427) min] (P = 0.001). Intraoperative blood loss [700 (500-1200) mL vs 500 (300-800) mL] (P = 0.009) and blood transfusion [975 (0-1250) mL vs 400 (0-800) mL] (P = 0.009) were higher in the PDTRIANGLE group. There was a higher incidence of surgical site infection (43.2% vs 12.5%) (P = 0.001) and postoperative diarrhea (54.1% vs 12.5%) (P = 0.001) in the PDTRIANGLE group. The rates of R0 resection and local recurrence, overall survival, and disease-free survival did not differ significantly between the two groups. CONCLUSION: The TRIANGLE technique is safe, with acceptable postoperative morbidities compared with standardized PD, but it does not improve prognosis for patients with resectable PDAC.

Loss of Claudin-1 incurred by DNMT aberration promotes pancreatic cancer progression.

Pancreatic cancer (PC) is one of the most malignant and deadly tumors of digestive system with complex etiology and pathogenesis. Dysregulations of oncogenes and tumor suppressors due to epigenetic modifications causally affect tumorogenesis; however the key tumor suppressors and their regulations in PC are only partially defined. In this study, we found that Claudin-1 (encoded by CLDN1 gene) was significantly suppressed in PC that correlated with a poor clinical prognosis. Claudin-1 knockdown enhanced PC cell proliferation, migration, and stemness. Pancreatic specific Cldn1 knockout in KPC (LSLKrasG12D/Pdx1-Cre/Trp53R172H+) and KC (LSLKrasG12D/Pdx1-Cre) mice reduced mouse survival, promoted acinar-to-ductal metaplasia (ADM) process, and accelerated the development of pancreatic intraepithelial neoplasia (PanIN) and PC. Further investigation revealed that Claudin-1 suppression was mainly caused by aberrant DNA methylatransferase 1 (DNMT1) and DNMT3A elevations and the resultant CLDN1 promoter hypermethylation, as a DNMT specific inhibitor SGI-1027 effectively reversed the Claudin-1 suppression and inhibited PC progression both in vitro and in vivo in a Claudin-1 preservation-dependent manner. Together, our data suggest that Claudin-1 functions as a tumor suppressor in PC and its epigenetic suppression due to DNMT aberrations is a crucial event that promotes PC development and progression.

Antibiotic prophylaxis with piperacillin-tazobactam reduces organ/space surgical site infection after pancreaticoduodenectomy: a retrospective and propensity score-matched analysis.

BACKGROUND: The occurrence of surgical site infection (SSI) after pancreaticoduodenectomy (PD) is still relatively high. The aim of this retrospective study is to evaluate the efficacy of piperacillin-tazobactam as perioperative prophylactic antibiotic on organ/space SSI for patients underwent PD. METHODS: Four hundred seven consecutive patients who underwent PD between January 2018 and December 2022 were enrolled and analyzed retrospectively. The univariate and multivariate analysis were used to identify independent risk factors of organ/space SSI. Postoperative complications were compared between the two groups according to the use of prophylactic antibiotics by a ratio of 1:1 propensity score-matched (PSM) analysis. RESULTS: Based on perioperative prophylactic antibiotic use, all 407 patients were divided into the ceftriaxone group (n = 192, 47.2%) and piperacillin-tazobactam group (n = 215, 52.8%). The rate of organ/space SSI was 31.2% with the choice of perioperative antibiotics (OR = 2.837, 95%CI = 1.802-4.465, P < 0.01) as one of independent risk factors. After PSM, there were similar baseline characteristics among the groups. Meanwhile, the piperacillin-tazobactam group had a significant lower rate of organ/space SSI compared to the ceftriaxone group both before and after PSM(P < 0.05). CONCLUSIONS: The adoption of piperacillin-tazobactam as perioperative prophylaxis for patients underwent PD reduced organ/space SSI significantly.

The novel HLA-C*03:651 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*03:651 differs from HLA-C*03:03:01:01 by one nucleotide in exon 4.

The Effect of Perioperative Dexamethasone on Postoperative Complications after Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. BACKGROUND: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. METHODS: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2 mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. RESULTS: Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. 134 patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference, -3.8; 95% CI, -8.4 to 0.7; P=0.100). The incidence of major complications (Clavien-Dindo grade ≥III) (12.7% vs. 16.0%, risk ratio 0.79; 95% CI, 0.44 to 1.43; P=0.439) and postoperative pancreatic fistula (25.4% vs. 31.3%, risk ratio 0.81; 95% CI, 0.55 to 1.19; P=0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3 mm (n=202), the CCI score was significantly lower in the dexamethasone group (mean difference, -6.4; 95% CI, -11.2 to -1.6; P=0.009). CONCLUSION: Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

Case-controlled study of tuberculosis in in-vitro fertilisation-embryo transfer and natural pregnancy.

OBJECTIVE: To improve the understanding of the clinical features and imaging characteristics of pregnant women with and without in-vitro fertilisation-embryo transfer combined with pulmonary tuberculosis (TB). METHODS: A retrospective analysis was conducted involving 50 patients with pregnancy who had pulmonary TB and were admitted to the Third People's Hospital of Kunming (China) between 1 January 2017 and 31 December 2021. These patients were divided into an in-vitro fertilisation and embryo transfer (IVF-ET) conception group and a natural conception group according to the conception method. The clinical and imaging data were then collected and compared. RESULTS: The mean age of the IVF-ET group (n = 13, 31.85 ± 5.84 years) was higher than in the natural conception group (n = 37, 27.05 ± 5.5 years). The proportions of fever, haematogenous TB and extrapulmonary TB in the IVF-ET group (92.31%, 84.62% and 76.92%, respectively) were higher than those in the natural conception group (40.54%,16.22%,27.03%,respectively). The percentage of patients with pregnancy who had intracranial TB (76.9%) in the IVF-ET group was higher than in the natural conception group (10.8%). The percentage of pregnancy terminations in the IVF-ET conception group (84.62%) was higher than in the natural conception group (48.65%). All the above results had statistically significant differences (p < 0.05). CONCLUSION: Overall, IVF-ET conception combined with extensive pulmonary TB lesions lead to heavy systemic toxic symptoms, severe disease and poor pregnancy outcomes. Therefore, screening for TB prior to performing IVF-ET is recommended.

Simultaneous deep transcriptome and proteome profiling in a single mouse oocyte.

Although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing, and mass spectrometry technology to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level, providing an important resource for understanding the relationship between transcription and translation in cells. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19,948 genes and 2,663 protein groups in single mouse oocytes. In particular, we analyzed the correlation of individual RNA and protein pairs, as well as the meiosis regulatory network with unprecedented depth, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, which could be productive for exploring transcriptional and translational regulatory features during oocyte meiosis.

Long non-coding RNA PRR7-AS1 promotes osteosarcoma progression via binding RNF2 to transcriptionally suppress MTUS1.

Introduction: Osteosarcoma is a common bone malignant tumor in adolescents with high mortality and poor prognosis. At present, the progress of osteosarcoma and effective treatment strategies are not clear. This study provides a new potential target for the progression and treatment of osteosarcoma. Methods: The relationship between lncRNA PRR7-AS1 and osteosarcoma was analyzed using the osteosarcoma databases and clinical sample testing. Cell function assays and tumor lung metastasis were employed to study the effects of PRR7-AS1 on tumorigenesis in vivo and in vitro. Potential downstream RNF2 of PRR7-AS1 was identified and explored using RNA pulldown and RIP. The GTRD and KnockTF database were used to predict the downstream target gene, MTUS1, and ChIP-qPCR experiments were used to verify the working mechanismy. Rescue experiments were utilized to confirm the role of MTUS1 in the pathway. Results: Deep mining of osteosarcoma databases combined with clinical sample testing revealed a positive correlation between lncRNA PRR7-AS1 and osteosarcoma progression. Knockdown of PRR7-AS1 inhibited osteosarcoma cell proliferation and metastasis in vitro and in vivo. Mechanistically, RNA pulldown and RIP revealed that PRR7-AS1 may bind RNF2 to play a cancer-promoting role. ChIP-qPCR experiments were utilized to validate the working mechanism of the downstream target gene MTUS1. RNF2 inhibited the transcription of MTUS1 through histone H2A lysine 119 monoubiquitin. Rescue experiments confirmed MTUS1 as a downstream direct target of PRR7-AS1 and RNF2. Discussion: We identified lncRNA PRR7-AS1 as an important oncogene in osteosarcoma progression, indicating that it may be a potential target for diagnosis and prognosis of osteosarcoma.

Caspase-3/GSDME mediated pyroptosis: A potential pathway for sepsis.

The inflammatory response is one of the host's mechanisms to combat pathogens. Normal and controlled inflammation can accelerate the clearance of pathogens. However, in sepsis, the host often exhibits an excessive inflammatory response to infection, leading to tissue and organ damage. Therefore, studying the mechanisms underlying the occurrence and development of sepsis is of significant importance. Pyroptosis is a form of programmed cell death (PCD) executed by the gasdermins (GSDMs) family, and its pro-inflammatory characteristics are considered a crucial component of the sepsis mechanism. Previous research on pyroptosis in sepsis has mainly focused on the caspase-1/4/5/11-GSDMD pathway, which has made significant progress. However, there is a lack of research on the roles of other GSDMs family members in sepsis. New research has revealed that the caspase-3/GSDME pathway can also mediate pyroptosis, playing important roles in cancer, other inflammatory diseases, and even some sepsis-related conditions. This discovery suggests the potential value of investigating caspase-3/GSDME in sepsis research. This review provides an overview of the role of the GSDMs family in infectious diseases, summarizes current research on the caspase-1/4/5/11-GSDMD pathway, describes the role of caspase-3 in sepsis, and discusses the research findings related to pyroptosis mediated by the caspase-3/GSDME pathway in cancer, inflammatory diseases, and sepsis-related conditions. The aim of this article is to propose the concept of caspase-3/GSDME as a potential target in sepsis research. Considering the role of this pathway in other diseases, including inflammatory conditions, and given the unique nature of sepsis as an inflammatory disease, the article suggests that this pathway may also play a role in sepsis. This hypothesis provides new insights and options for future sepsis research, although direct experiments are needed to validate this hypothesis.

Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria.

OBJECTIVES: This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microbiota by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. METHODS: In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B14, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine - exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. RESULTS: Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 µM nicotine and 10 µM cotinine concentrations reduced total protein cargo of Gram (-) - 25285 and B14 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 µM nicotine, and 5 or 10 µΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. CONCLUSIONS: Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.

E3 ubiquitin ligase RNF187 promotes growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84.

Ubiquitination is the most common post-translational modification and is essential for various cellular regulatory processes. RNF187, which is known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 can promote the proliferation and migration of various tumor cells. However, whether it has a similar role in regulating spermatogonia is not clear. This study explored the role and molecular mechanism of RNF187 in a mouse spermatogonia cell line (GC-1). We found that RNF187 knockdown reduced the proliferation and migration of GC-1 cells and promoted their apoptosis. RNF187 overexpression significantly increased the proliferation and migration of GC-1 cells. In addition, we identified Keratin36/Keratin84 (KRT36/KRT84) as interactors with RNF187 by co-immunoprecipitation and mass spectrometry analyses. RNF187 promoted GC-1 cell growth by degrading KRT36/KRT84 via lysine 48-linked polyubiquitination. Subsequently, we found that KRT36 or KRT84 overexpression significantly attenuated proliferation and migration of RNF187-overexpressing GC-1 cells. In summary, our study explored the involvement of RNF187 in regulating the growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84. This may provide a promising new strategy for treating infertility caused by abnormal spermatogonia development.

Laparoscopic versus Open Inguinal Hernia Repair in Aging Patients: A Propensity Score Matching-Based Retrospective Study.

Objective: Although laparoscopic repair has been widely carried out and promoted due to its minimally invasive advantages, open surgery is still popular compared to elderly patients. This study aims to compare the outcomes of laparoscopic (LIHR) vs open repair of inguinal hernias (OIHR) in elderly patients. Methods: A retrospective analysis of the database was performed to identify elderly patients, from January 2021 through December 2022, who underwent surgery for an inguinal hernia. After a 1:1 propensity score matching (PSM) with a caliper of 0.1 was conducted to balance potential bias, binary logistic regressions were used for categorical and continuous outcomes. Results: After PSM, 78 pairs of elderly patients were enrolled in this study, and there were no significant differences in baseline between LIHR and OIHR groups. Compared to OIHR, univariable and multivariable logistic regression analysis showed that LIHR was independently affected for reducing intraoperative hemorrhage (OR = 0.06, 95% CI: 0.02-0.18, P < 0.001) and shortening postoperative hospitalization time (OR = 0.29, 95% CI: 0.15-0.57, P < 0.001) in elderly patients. Furthermore, LIHR (OR = 0.28, 95% CI: 0.14-0.57, P < 0.001) and age (OR = 0.89, 95% CI: 0.82-0.96, P = 0.002) were independent affecting factors for relieving postoperative pain. Meanwhile, no obvious differences were detected in postoperative complications [LIHR 7.7% (6/78) vs OIHR 14.1% (11/78), P = 0.199]. Conclusion: LIHR was closely associated with reducing intraoperative hemorrhage and shortening postoperative hospitalization time. Whilst LIHR and age were independently affecting factors for relieving postoperative pain.

A promising tool for clinical diagnostics: Dual-emissive carbonized polymer dots based cross-linking enhanced emission for sensitive detection of alkaline phosphatase and butyrylcholinesterase.

Compared with single signal readout, dual-signal readout commendably corrects the impact of systematic or background error, achieving more accurate results for the diagnosis of many diseases. This work aimed to design and prepare dual-emissive fluorescent probes for the construction of ratiometric fluorescence biosensors to detect liver disease biomarkers. Sodium alginate (SA) with numerous potential sub-fluorophores and active sites and 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP) with macrocyclic conjugated structures were introduced to prepare the carbonized polymer dots (CPDs) with red/blue dual emission based on the cross-linking enhanced emission (CEE) effect and the luminescence of macrocyclic conjugated structures. The ratiometric fluorescence sensing systems were constructed by integrating the specific response of CPDs to Cu2+ and the affinity difference of Cu2+ to substrates or products of enzymes. The sensing systems, CPDs/Cu2+/PPi and CPDs/Cu2+/BTCh, were designed to detect liver disease biomarkers, alkaline phosphatase (ALP) and butyrylcholinesterase (BChE), respectively. The limit of detection for ALP and BChE was 0.35 U/L and 0.19 U/L, respectively. The proposed sensors were successfully applied to human serum samples from different health stages with satisfactory recoveries. These results demonstrate the successful design of a novel dual-emissive fluorescent probe and provide a feasible strategy for clinical detection.

Hydrothermal Growth of an Al-Doped α-Ga2O3 Nanorod Array and Its Application in Self-Powered Solar-Blind UV Photodetection Based on a Photoelectrochemical Cell.

Herein, we successfully fabricated an Al-doped α-Ga2O3 nanorod array on FTO using the hydrothermal and post-annealing processes. To the best of our knowledge, it is the first time that an Al-doped α-Ga2O3 nanorod array on FTO has been realized via a much simpler and cheaper way than that based on metal-organic chemical vapor deposition, magnetron sputtering, molecular beam epitaxy, and pulsed laser deposition. And, a self-powered Al-doped α-Ga2O3 nanorod array/FTO photodetector was also realized as a photoanode at 0 V (vs. Ag/AgCl) in a photoelectrochemical (PEC) cell, showing a peak responsivity of 1.46 mA/W at 260 nm. The response speed of the Al-doped device was 0.421 s for rise time, and 0.139 s for decay time under solar-blind UV (260 nm) illumination. Compared with the undoped device, the responsivity of the Al-doped device was ~5.84 times larger, and the response speed was relatively faster. When increasing the biases from 0 V to 1 V, the responsivity, quantum efficiency, and detectivity of the Al-doped device were enhanced from 1.46 mA/W to 2.02 mA/W, from ~0.7% to ~0.96%, and from ~6 × 109 Jones to ~1 × 1010 Jones, respectively, due to the enlarged depletion region. Therefore, Al doping may provide a route to enhance the self-powered photodetection performance of α-Ga2O3 nanorod arrays.

HGECDA: A Heterogeneous Graph Embedding Model for CircRNA-Disease Association Prediction.

Circular RNAs (circRNAs) are specifically and abnormally expressed in disease tissues, and thus can be used as biomarkers to diagnose relevant diseases. Predicting circRNA-disease associations will provide essential clues to reveal molecular mechanisms of disease development and discover novel therapeutic targets. Existing algorithms ignore the heterogeneous biological association information related to microRNAs (miRNAs). Based on a heterogeneous graph embedding model, a novel circRNA-disease association prediction method called HGECDA is developed in this paper. The heterogeneous graph network containing circRNA-miRNA-disease association information is first constructed. To sample the heterogeneous information, the meta-path-based random walk that can capture the relevance between various types of nodes is employed. Then, the path embedding model based on skip-gram and random negative sampling is built to acquire the initial feature vectors of circRNAs and diseases. Finally, the CosMulformer model with linearized self-attention and Hadamard product is designed to obtain the circRNA-disease interaction vectors and conduct the prediction task. Experimental results demonstrate the critical role of miRNA in enriching the information of the feature space, the effectiveness of the CosMulformer model in picking out deep local interaction features, and the feasibility of the Hadamard product chosen as the integration pattern in the CosMulformer model. Compared with existing state-of-the-art methods on the same dataset, HGECDA performs better than the other seven algorithms. Moreover, the case studies about breast cancer and colorectal cancer demonstrate the practical value of HGECDA in predicting potential circRNA-disease associations.

Interferon-γ regulates immunosuppression in septic mice by promoting the Warburg effect through the PI3K/AKT/mTOR pathway.

BACKGROUND: The main cause of high mortality from sepsis is that immunosuppression leads to life-threatening organ dysfunction, and reversing immunosuppression is key to sepsis treatment. Interferon γ (IFNγ) is a potential therapy for immunosuppression of sepsis, promoting glycolysis to restore metabolic defects in monocytes, but the mechanism of treatment is unclear. METHODS: To explore the immunotherapeutic mechanism of IFNγ, this study linked the Warburg effect (aerobic glycolysis) to immunotherapy for sepsis and used cecal ligation perforation (CLP) and lipopolysaccharide (LPS) to stimulate dendritic cells (DC) to establish in vivo and in vitro sepsis models, Warburg effect inhibitors (2-DG) and PI3K pathway inhibitors (LY294002) were used to explore the mechanism by which IFNγ regulates immunosuppression in mice with sepsis through the Warburg effect. RESULTS: IFNγ markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNγ-treated mice had significantly increased the percentages of positive costimulatory receptor CD86 on Dendritic cells expressing and expression of splenic HLA-DR. IFNγ markedly reduced DC-cell apoptosis by upregulating the expression of Bcl-2 and downregulating the expression of Bax. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNγ -treated mice. IFNγ treatment reduced the expression of autophagosomes in DC cells. IFNγ significant reduce the expression of Warburg effector-related proteins PDH, LDH, Glut1, and Glut4, and promote glucose consumption, lactic acid, and intracellular ATP production. After the use of 2-DG to suppress the Warburg effect, the therapeutic effect of IFNγ was suppressed, demonstrating that IFNγ reverses immunosuppression by promoting the Warburg effect. Moreover, IFNγ increased the expression of phosphoinositide 3-kinases (PI3K), protein kinase B (Akt), rapamycin target protein (mTOR), hypoxia-inducible factor-1 (HIF-1α), pyruvate dehydrogenase kinase (PDK1) protein, the use of 2-DG and LY294002 can inhibit the expression of the above proteins, LY294002 also inhibits the therapeutic effect of IFNγ. CONCLUSIONS: It was finally proved that IFNγ promoted the Warburg effect through the PI3K/Akt/mTOR pathway to reverse the immunosuppression caused by sepsis. This study elucidates the potential mechanism of the immunotherapeutic effect of IFNγ in sepsis, providing a new target for the treatment of sepsis.

The role of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy in patients with obstructive jaundice.

Background: The role of preoperative biliary drainage (PBD) on obstructive jaundice patients is still controversial. The aim of this retrospective study is to clarify the effect of PBD on postoperative outcomes of pancreaticoduodenectomy (PD) and explore a reasonable PBD strategy for periampullary carcinomas (PAC) patients with obstructive jaundice before surgery. Methods: A total of 148 patients with obstructive jaundice who underwent PD were enrolled in this research and divided into drainage group and no-drainage group according to whether they received PBD. Patients who received PBD were classified into long-term group (>2 weeks) and short-term group (≤2 weeks) according to PBD duration. The clinical data of patients were statistically compared between groups to explore the influence of PBD and its duration. Analysis of pathogens in bile and peritoneal fluid was performed to probe the role of bile pathogens in opportunistic pathogenic bacterial infection after PD. Results: Of all, 98 patients underwent PBD. The mean duration between drainage and surgery was 13 days. Regarding postoperative outcomes, the incidence of postoperative intra-abdominal infection was significantly higher in the drainage group than the no-drainage group (P=0.026). In patients with total bilirubin (TB) less than 250 µmol/L, postoperative intra-abdominal infection was more frequently observed in the drainage group compared to the no-drainage group (P=0.022). Compared to the short-term drainage group, the proportion of positive ascites culture was significantly higher in the long-term drainage group (P=0.022). There were no statistically significant differences in postoperative complications between short-term group and no-drainage group. The most frequent pathogens detected in bile were Klebsiella pneumoniae, hemolytic Streptococcus and Enterococcus faecalis. The most commonly detected pathogens in peritoneal fluid were Klebsiella pneumoniae, Enterococcus faecalis and Staphylococcus epidermidis which appeared to have a high agreement with pathogens in preoperative bile cultures. Conclusions: Routine PBD should not be performed in obstructive jaundice PAC patients with TB less than 250 µmol/L. For patients with indications for PBD, the drainage duration should be controlled within 2 weeks. Bile bacteria may represent a major source of opportunistic pathogenic bacteria infection after PD.

The role of GLUT2 in glucose metabolism in multiple organs and tissues.

The glucose transporter family has an important role in the initial stage of glucose metabolism; Glucose transporters 2 (GLUTs, encoded by the solute carrier family 2, SLC2A genes) is the major glucose transporter in ß-cells of pancreatic islets and hepatocytes but is also expressed in the small intestine, kidneys, and central nervous system; GLUT2 has a relatively low affinity to glucose. Under physiological conditions, GLUT2 transports glucose into cells and allows the glucose concentration to reach balance on the bilateral sides of the cellular membrane; Variation of GLUT2 is associated with various endocrine and metabolic disorders; In this study, we discussed the role of GLUT2 in participating in glucose metabolism and regulation in multiple organs and tissues and its effects on maintaining glucose homeostasis.

DNA-AgNC Loaded Liposomes for Measuring Cerebral Blood Flow Using Two-Photon Fluorescence Correlation Spectroscopy.

Unraveling the transport of drugs and nanocarriers in cerebrovascular networks is important for pharmacokinetic and hemodynamic studies but is challenging due to the complexity of sensing individual particles within the circulatory system of a live animal. Here, we demonstrate that a DNA-stabilized silver nanocluster (DNA-Ag16NC) that emits in the first near-infrared window upon two-photon excitation in the second NIR window can be used for multiphoton in vivo fluorescence correlation spectroscopy for the measurement of cerebral blood flow rates in live mice with high spatial and temporal resolution. To ensure bright and stable emission during in vivo experiments, we loaded DNA-Ag16NCs into liposomes, which served the dual purposes of concentrating the fluorescent label and protecting it from degradation. DNA-Ag16NC-loaded liposomes enabled the quantification of cerebral blood flow velocities within individual vessels of a living mouse.