Delayed gastric emptying after laparoscopic pancreaticoduodenectomy: a single-center experience of 827 cases.

BACKGROUND: Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. METHODS: This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. RESULTS: A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p < 0.001) were independent significant risk factors for DGE. Seventy-six (53.5%) patients were diagnosed with primary DGE, whereas 66 (46.5%) patients had DGE secondary to concomitant complications. Higher body mass index, soft pancreatic texture, and perioperative transfusion were independent risk factors for secondary DGE. Hospital stay and drainage tube removal time were significantly longer in the DGE and secondary DGE groups. CONCLUSION: Identifying patients at an increased risk of DGE and secondary DGE can be used to intervene earlier, avoid potential risk factors, and make more informed clinical decisions to shorten the duration of perioperative management.

A CARM1 Inhibitor Potently Suppresses Breast Cancer Both In Vitro and In Vivo.

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

Protective effects of COVID-19 vaccination in splenectomized patients with immune thrombocytopenia.

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.

CDK4/6 inhibition sensitizes MEK inhibition by inhibiting cell cycle and proliferation in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.

Enhanced acrylic gauge with five eccentric circles for optimizing CT angiography spatial resolution via Taguchi's methodology.

BACKGROUND: Cerebral examination via CTA is always the first choice for patients with unexpected brain injury or different types of brain lesions to detect ruptured hemangiomas, vascular infarcts, or other brain tissue lesions. OBJECTIVE: This study innovated the acrylic gauge with five eccentric circles for computed tomography angiography (CTA) analysis to optimize the spatial resolution via Taguchi's methodology. METHODS: The customized gauge was revised from the V-shaped slit gauge and transferred into five eccentric circles' slit gauge. The gauge was assembled with another six acrylic layers to simulate the human head. Taguchi's L18 orthogonal array was adopted to optimize the spatial resolution of CTA imaging quality. In doing so, six essential factors of CTA are kVp, mAs, spiral rotation pitch, FOV, rotation time of the CT and reconstruction filter, and each factor has either two or three levels to organize into eighteen combinations to simulate the full factor combination of 486 (21 × 35 = 486) times according to Taguchi's recommendation. Three well-trained radiologists ranked the gauge's 18 CTA scanned imaging qualities according to contrast, sharpness, and spatial resolution and derived the unique fish-bone-plot of six factors for further analysis. The optimal factor combination of CTA was proven by follow-up verification and ANOVA to obtain this study's dominant or minor factor. RESULTS: The optimal factor combination of CTA was A2 (120 kVp), B3 (200 mAs), C1 (Pitch 0.6), D2 (FOV 220 mm2), E1 (rotation time 0.33 s), and F3 (Brain sharp, UC). Furthermore, deriving a quantified MDD (minimum detectable difference) to imply the spatial resolution of CTA, a semiauto profile analysis program run in MATLAB and OriginPro was recommended to evaluate the MDD and to suppress the manual error in calculation. Eventually, the derived MDDs of the conventional and optimal factor combinations of CTA were 2.35 and 2.26 mm, respectively, in this study. CONCLUSION: Taguchi's methodology was found applicable for quantifying the CTA imaging quality in practical applications.

Independent external validation and comparison of existing pancreatic fistula risk scores after laparoscopic pancreaticoduodenectomy with Bing's pancreaticojejunostomy.

BACKGROUND: The fistula risk score (FRS) is the widely acknowledged prediction model for clinically relevant postoperative pancreatic fistula (CR-POPF). In addition, the alternative FRS (a-FRS) and updated alternative FRS (ua-FRS) have been developed. This study performed external validation and comparison of these 3 models in patients who underwent laparoscopic pancreaticoduodenectomy (LPD) with Bing's pancreaticojejunostomy. METHODS: The FRS total points and predictive probabilities of a-FRS and ua-FRS were retrospectively calculated using patient data from a completed randomized controlled trial. Postoperative pancreatic fistula (POPF) and CR-POPF were defined according to the 2016 International Study Group of Pancreatic Surgery criteria. The correlations of the 4 risk items of the FRS model with CR-POPF and POPF were analyzed and represented using the Cramer V coefficient. The performance of the 3 models was measured using the area under the curve (AUC) and calibration plot and compared using the DeLong test. RESULTS: This study enrolled 200 patients. Pancreatic texture and pathology had discrimination for CR-POPF (Cramer V coefficient: 0.180 vs 0.167, respectively). Pancreatic duct diameter, pancreatic texture, and pathology had discrimination for POPF (Cramer V coefficient: 0.357 vs 0.322 vs 0.257, respectively). Only the calibration of a-FRS predicting CR-POPF was good. The differences among the AUC values of the FRS, a-FRS, and ua-FRS were not statistically significant (CR-POPF: 0.687 vs 0.701 vs 0.710, respectively; POPF: 0.733 vs 0.741 vs 0.750, respectively). After recalibrating, the ua-FRS got sufficient calibration, and the AUC was 0.713 for predicting CR-POPF. CONCLUSION: For LPD cases with Bing's pancreaticojejunostomy, the 3 models predicted POPF with better discrimination than predicting CR-POPF. The recalibrated ua-FRS had sufficient discrimination and calibration for predicting CR-POPF.

CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development.

Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.

Research on the role and mechanism of IL-17 in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is one of the primary causes of low back pain (LBP), which seriously affects patients' quality of life. In recent years, interleukin (IL)-17 has been shown to be highly expressed in the intervertebral disc (IVD) tissues and serum of patients with IDD, and IL-17A has been shown to promote IDD through multiple pathways. We first searched databases such as PubMed, Cochrane, Embase, and Web of Science using the search terms "IL-17 or interleukin 17″ and "intervertebral discs". The search period ranged from the inception of the databases to December 2023. A total of 24 articles were selected after full-text screening. The main conclusion of the clinical studies was that IL-17A levels are significantly increased in the IVD tissues and serum of IDD patients. The results from the in vitro studies indicated that IL-17A can activate signaling pathways such as the NF-κB and MAPK pathways; promote inflammatory responses, extracellular matrix degradation, and angiogenesis; and inhibit autophagy in nucleus pulposus cells. The main finding of the in vivo experiments was that puncture of animal IVDs resulted in elevated levels of IL-17A within the IVD, thereby inducing IDD. Clinical studies, in vitro experiments, and in vivo experiments confirmed that IL-17A is closely related to IDD. Therefore, drugs that target IL-17A may be novel treatments for IDD, providing a new theoretical basis for IDD therapy.

Pestalotiopsis jiangsuensis sp. nov. Causing Needle Blight on Pinus massoniana in China.

Pinus massoniana Lamb. is an important, common afforestation and timber tree species in China. Species of Pestalotiopsis are well-known pathogens of needle blight. In this study, the five representative strains were isolated from needle blight from needles of Pi. massoniana in Nanjing, Jiangsu, China. Based on multi-locus phylogenetic analyses of the three genomic loci (ITS, TEF1, and TUB2), in conjunction with morphological characteristics, a new species, namely Pestalotiopsis jiangsuensis sp. nov., was described and reported. Pathogenicity tests revealed that the five representative strains of the species described above were pathogenic to Pi. massoniana. The study revealed the diversity of pathogenic species of needle blight on Pi. massoniana. This is the first report of needle blight caused by P. jiangsuensis on Pi. massoniana in China and worldwide. This provides useful information for future research on management strategies of this disease.

Textbook oncologic outcomes are associated with increased overall survival in patients with pancreatic head cancer after undergoing laparoscopic pancreaticoduodenectomy.

BACKGROUND: Textbook oncologic outcomes (TOO) have been used to evaluate long-term oncologic outcomes for patients after pancreaticoduodenectomy (PD) but not laparoscopic pancreaticoduodenectomy (LPD). The aim of the study was to assess the prognostic value of TOO for patients with pancreatic head cancer undergoing LPD and discuss the risk factors associated with achieving TOO. METHODS: Patients with pancreatic head cancer who underwent LPD in West China Hospital from January 2015 to May 2022 were consecutively enrolled. TOO was defined as achieving R0 resection, examination of ≥ 12 lymph nodes, no prolonged length of stay, no 30-day readmission/death, and receiving adjuvant chemotherapy. Survival analysis was used to determine the prognostic value of a TOO on overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify the risk factors of a TOO. The rates of a TOO and of each indicator were compared in patients who suffered or not from delayed gastric emptying (DGE). RESULTS: A total of 44 (25.73%) patients achieved TOO which was associated with improved median OS (TOO 32 months vs. non-TOO 20 months, P = 0.034) and a better RFS (TOO 19 months vs. non-TOO 13 months, P = 0.053). Patients suffering from DGE [odds ratio (OR) 4.045, 95% CI 1.151-14.214, P = 0.029] were independent risk factors for TOO. In addition, patients with DGE after surgery had a significantly lower rate of TOO (P = 0.015) than patients without DGE. CONCLUSIONS: As there were significant differences between patients who achieved TOO or not, TOO is a good indicator for long-term oncologic outcomes in patients with pancreatic head cancer after undergoing LPD. DGE is the risk factor for achieving TOO, so it is important to prevent the DGE after LPD to improve the rate of TOO.

Real-time fluorescence-guided adhesiolysis with indocyanine green in intra-abdominal surgery (with video).

Intra-abdominal adhesions have consistently posed a challenge for surgeons during procedures. This study aims to investigate the feasibility of utilizing indocyanine green (ICG) in conjunction with near-infrared imaging for the detection of intra-abdominal adhesions. In vitro, we analyzed factors affecting ICG fluorescence. We divided SD rats into groups to study ICG excretion in different digestive tract regions. Additionally, we reviewed surgical videos from previous cholecystectomy cases, categorizing them by ICG injection timing and assessing fluorescence imaging in various digestive tract regions. Finally, we preoperatively injected ICG into two cholecystectomized patients with abdominal adhesions, guiding intraoperative adhesiolysis with near-infrared fluorescence imaging. In vitro, we observed a significant influence of protein and ICG concentrations on ICG fluorescence intensity. Our rat experiments unveiled a strong and highly significant correlation (Kendall's tau-b = 1, P < 0.001) between the timing of ICG injection and the farthest point of intestinal fluorescence. A retrospective case analysis further validated this finding (Kendall's tau-b = 0.967, P < 0.001). Under the guidance of fluorescence navigation, two cholecystectomized patients with intra-abdominal adhesions successfully underwent adhesiolysis, and no postoperative complications occurred. The intraoperative combination of ICG with near-infrared fluorescence imaging effectively enhances the visibility of the liver, bile ducts, and various segments of the gastrointestinal tract while providing real-time navigation. This real-time fluorescence guidance has the potential to aid surgeons in the dissection of intra-abdominal adhesions.

Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy (LPDEXCEPT): protocol for a multicentre superiority randomised controlled trial.

INTRODUCTION: Postoperative pancreatic fistula (POPF) remains one of the most severe complications of laparoscopic pancreaticoduodenectomy (LPD). Theoretically, transecting the pancreatic neck more distally has both advantages (more blood supply, and more central pancreatic duct) and disadvantages (maybe smaller the pancreatic duct) in preventing POPF. This theoretical contradiction pushed us to organise this trial to explore the impact of the level of pancreatic transection in clinical practice. We conduct this randomised trial with the hypothesis that extended pancreatic neck transection has superiority to conventional pancreatic neck transection. METHODS AND ANALYSIS: The LPDEXCEPT (Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy) trial is a multicentre, randomised-controlled, open-label, superiority trial in 4 centres whose annual surgical volume for LPD is more than 25 cases with pancreatic surgeons who had completed their learning curve. A total of 154 patients who meet the inclusive and exclusive criteria are randomly allocated to the extended pancreatic neck transection group or conventional pancreatic neck transection group in a 1:1 ratio. The stratified randomised block design will be applied, with stratified factors are surgical centre and the diameter of the main pancreatic duct measured by preoperative CT scan (preMPD). The primary outcome is the incidence of the clinically relevant pancreatic fistula. ETHICS AND DISSEMINATION: Ethics Committee on Biomedical Research of West China Hospital of Sichuan University has approved this trial in March 2023 (approval no. 2023-167). Results of this trial will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: NCT05808894.

Decoding surgical skill: an objective and efficient algorithm for surgical skill classification based on surgical gesture features -experimental studies.

BACKGROUND: Various surgical skills lead to differences in patient outcomes and identifying poorly skilled surgeons with constructive feedback contributes to surgical quality improvement. The aim of the study was to develop an algorithm for evaluating surgical skills in laparoscopic cholecystectomy based on the features of elementary functional surgical gestures (Surgestures). MATERIALS AND METHODS: Seventy-five laparoscopic cholecystectomy videos were collected from 33 surgeons in five hospitals. The phase of mobilization hepatocystic triangle and gallbladder dissection from the liver bed of each video were annotated with 14 Surgestures. The videos were grouped into competent and incompetent based on the quantiles of modified global operative assessment of laparoscopic skills (mGOALS). Surgeon-related information, clinical data, and intraoperative events were analyzed. Sixty-three Surgesture features were extracted to develop the surgical skill classification algorithm. The area under the receiver operating characteristic curve of the classification and the top features were evaluated. RESULTS: Correlation analysis revealed that most perioperative factors had no significant correlation with mGOALS scores. The incompetent group has a higher probability of cholecystic vascular injury compared to the competent group (30.8 vs 6.1%, P =0.004). The competent group demonstrated fewer inefficient Surgestures, lower shift frequency, and a larger dissection-exposure ratio of Surgestures during the procedure. The area under the receiver operating characteristic curve of the classification algorithm achieved 0.866. Different Surgesture features contributed variably to overall performance and specific skill items. CONCLUSION: The computer algorithm accurately classified surgeons with different skill levels using objective Surgesture features, adding insight into designing automatic laparoscopic surgical skill assessment tools with technical feedback.

Effect of low-molecular-weight heparin on placenta-mediated fetal growth restriction in a tertiary referral hospital: A 7-year retrospective cohort study.

OBJECTIVE: To investigate the effect of low-molecular-weight heparin (LMWH) on placenta-mediated fetal growth restriction (FGR). METHODS: A cohort of 570 pregnant women diagnosed with placenta-mediated FGR were enrolled from January 1, 2015 through to December 31, 2021. A birth database, including demographic data, antenatal complications, and detailed delivery and newborn data, was created to collect variables from the Hospital Information System (HIS) Database. The unique personal registration number, assigned to each patient on first registration with HIS in the West China Second University Hospital, was used to link these patients. LMWH use was defined as at least 1-week prescription from diagnosis of placenta-mediated FGR. Pregnant women received LMWH (Enoxaparin 4000 IU/day) by self-administered subcutaneous injection only when they agreed and signed informed consent. Primary outcome was intrauterine fetal death after 20 weeks of pregnancy. Secondary outcomes included preterm birth (PB), Apgar score less than 7 at 1 min, admission to neonatal intensive care unit (NICU), and birth weight. Logistic regression analysis was conducted to compute adjusted odds ratio (aOR) with 95% confidence intervals (CI) for outcomes. RESULTS: After controlling for confounders, LMWH use was associated with a decreased risk of intrauterine fetal death (aOR 2.49, 95% CI 1.35-4.57, P = 0.003), PB before 37 weeks of pregnancy (aOR 3.35, 95% CI 2.14-5.23, P < 0.001), PB before 34 weeks of pregnancy (aOR 2.25, 95% CI 1.36-3.74, P = 0.002), Apgar score less than 7 at 1 min (aOR 2.25, 95% CI 1.36-3.74, P = 0.002), NICU admission (aOR 2.29, 95% CI 1.48-3.55, P < 0.001). Using LMWH increased the mean birth weight in PB before 32 weeks of pregnancy (mean ± standard deviation [SD] 1126.4 ± 520.0 g, P = 0.020), PB before 37 weeks of pregnancy (mean ± SD 1563.9 ± 502.7 g, P = 0.019), early-onset FGR (mean ± SD 2125.2 ± 665.7 g, P < 0.001), late-onset FGR (mean ± SD 2343.4 ± 507.9, P < 0.001), and non-severe FGR (mean ± SD 2231.1 ± 607.2 g, P < 0.001). CONCLUSION: Use of LMWH can significantly improve the fetal and neonatal outcomes among pregnant women with placenta-mediated FGR, particularly reducing the risk of intrauterine fetal death.

Mercury-containing preparations attenuate neutrophil extracellular trap formation in mice and humans through inhibiting the ERK1/2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Neutrophil extracellular trap (NET) formation plays a crucial role in wound healing disorders, including chronic skin ulcers and diabetic foot ulcers (DFUs). Over the years, traditional Chinese topical medications, such as Cinnabar (composed of HgS and soluble mercury salt) and hydrargyria oxydum rubrum (containing HgO and soluble mercury salt), have been utilized for treating these ailments. Nevertheless, the fundamental processes remain mostly ambiguous. AIM OF THE STUDY: This study sought to investigate the potential effects of topical mercury-containing preparations on the process of NET formation. MATERIALS AND METHODS: Neutrophils isolated from healthy individuals and mouse models of type 1 and type 2 diabetes were cultured with phorbol 12-myristate 13-acetate (PMA), both with and without the mercury-containing preparations (MCP). The formation of NETs was monitored using confocal and scanning electron microscopes. Immunofluorescence and fluorescent probes were employed to assess the levels of citrulline histone H3 (Cit-H3) and intracellular reactive oxygen species (ROS), respectively. The impact of MCP extracts on cytokine expression, peptidylarginine deiminase 4 (PAD4), and myeloperoxidase (MPO) was measured through Luminex and ELISA assays. Phagocytosis of human neutrophils was analyzed using Flow Cytometry. Finally, the phosphorylation levels of ERK were detected by western blotting. RESULTS: Treatment with MCP led to a reduction in PAD4, Cit-H3, and MPO expressions in neutrophils, consequently inhibiting PMA-induced NET formation. MCP treatment also dampened ERK1/2 activation in neutrophils. Furthermore, MCP exhibited inhibitory effects on the secretion of the cytokine IL-8 and ROS production while enhancing neutrophil phagocytosis. CONCLUSION: Our findings suggest that MCP can mitigate the release of NETs, likely by suppressing the ERK1/2 signaling pathway.

The safety and anti-tumor effect of multiple peptides-pulsed dendritic cells combined with induced specific cytotoxic T lymphocytes for patients with solid tumors.

Objective: The aim of this study was to explore the safety and efficacy of multiple peptide-pulsed autologous dendritic cells (DCs) combined with cytotoxic T lymphocytes (CTLs) in patients with cancer. Methods: Five patients diagnosed with cancer between November 2020 and June 2021 were enrolled and received DC-CTLs therapy. Peripheral blood was collected and antigenic peptides were analyzed. The phenotype and function of DC-CTLs and the immune status of patients were detected using flow cytometry or IFN-γ ELISPOT analysis. Results: DCs acquired a mature phenotype and expressed high levels of CD80, CD86, CD83, and HLA-DR after co-culture with peptides, and the DC-CTLs also exhibited high levels of IFN-γ. Peripheral blood mononuclear cells from post-treatment patients showed a stronger immune response to peptides than those prior to treatment. Importantly, four of five patients maintained a favorable immune status, of which one patient's disease-free survival lasted up to 28.2 months. No severe treatment-related adverse events were observed. Conclusion: Our results show that multiple peptide-pulsed DCs combined with CTLs therapy has manageable safety and promising efficacy for cancer patients, which might provide a precise immunotherapeutic strategy for cancer.

Inverse Problem Algorithm-Based Time-Resolved Imaging of Head and Neck Computed Tomography Angiography Contrast Kinetics with Clinical Testification.

This study mitigated the challenge of head and neck CT angiography by IPA-based time-resolved imaging of contrast kinetics. To this end, 627 cerebral hemorrhage patients with dizziness, brain aneurysm, stroke, or hemorrhagic stroke diagnosis were randomly categorized into three groups, namely, the original dataset (450), verification group (112), and in vivo testified group (65), in the Affiliated BenQ Hospital of Nanjing Medical University. In the first stage, seven risk factors were assigned: age, CTA tube voltage, body surface area, heart rate per minute, cardiac output blood per minute, the actual injected amount of contrast media, and CTA delayed trigger timing. The expectation value of the semi-empirical formula was the CTA number of the patient's left artery (LA). Accordingly, 29 items of the first-order nonlinear equation were calculated via the inverse problem analysis (IPA) technique run in the STATISTICA 7.0 program, yielding a loss function and variance of 3.1837 and 0.8892, respectively. A dimensionless AT was proposed to imply the coincidence, with a lower AT indicating a smaller deviation between theoretical and practical values. The derived formula was confirmed for the verification group of 112 patients, reaching high coincidence, with average ATavg and standard deviation values of 3.57% and 3.06%, respectively. In the second stage, the formula was refined to find the optimal amount of contrast media for the CTA number of LA approaching 400. Finally, the above procedure was applied to head and neck CTA images of the third group of 65 patients, reaching an average CTA number of LA of 407.8 ± 16.2 and finding no significant fluctuations.

Gas-Pressurized Torrefaction of Lignocellulosic Solid Wastes: Deoxygenation and Aromatization Mechanisms of Cellulose.

A novel gas-pressurized (GP) torrefaction method at 250 °C has recently been developed that realizes the deep decomposition of cellulose in lignocellulosic solid wastes (LSW) to as high as 90% through deoxygenation and aromatization reactions. However, the deoxygenation and aromatization mechanisms are currently unclear. In this work, these mechanisms were studied through a developed molecular structure calculation method and the GP torrefaction of pure cellulose. The results demonstrate that GP torrefaction at 250 °C causes 47 wt.% of mass loss and 72 wt.% of O removal for cellulose, while traditional torrefaction at atmospheric pressure has almost no impact on cellulose decomposition. The GP-torrefied cellulose is determined to be composed of an aromatic furans nucleus with branch aliphatic C through conventional characterization. A molecular structure calculation method and its principles were developed for further investigation of molecular-level mechanisms. It was found 2-ring furans aromatic compound intermediate is formed by intra- and inter-molecular dehydroxylation reactions of amorphous cellulose, and the removal of O-containing function groups is mainly through the production of H2O. The three-ring furans aromatic compound intermediate and GP-torrefied cellulose are further formed through the polymerization reaction, which enhances the removal of ketones and aldehydes function groups in intermediate torrefied cellulose and form gaseous CO and O-containing organic molecules. A deoxygenation and aromatization mechanism model was developed based on the above investigation. This work provides theoretical guidance for the optimization of the gas-pressurized torrefaction method and a study method for the determination of molecular-level structure and the mechanism investigation of the thermal conversion processes of LSW.

Unleashing Breast Cancer Progression: miR-455-5p's Targeting of SOCS3 Drives Proliferation, Migration, and Invasion.

OBJECTIVES: We aim to investigate the regulatory mechanisms of miR-455-5p/SOCS3 pathway that underlie the proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-455-5p expression in breast cancer tissues and cell lines. CCK8 and Transwell assays were conducted to assess the effects of miR-455-5p on breast cancer line proliferation, migration, and invasion. SOCS3 expression level in breast cancer tissues and cell lines was determined by qPCR and western blotting. The targeting relationship between miR-455-5p and SOCS3 was determined by dual luciferase reporter gene assay in different breast cancer cell lines. Finally, the upstream and downstream regulatory association between miR-455-5p and SOCS3 was confirmed in breast cancer cells by CCK8, western blot, and Transwell assays. RESULTS: MiR-455-5p expression was up-regulated in breast cancer tissues; miR-455-5p regulates TNBC proliferation, migration, and invasion of TNBC. SOCS3 was the direct target of miR-455-5p and was down-regulated in breast cancer. Interference with SOCS3 reversed the inhibitory effect of the miR-455-5p inhibitor on breast cancer cells' malignant potential. CONCLUSION: MiR-455-5p promotes breast cancer progression by targeting the SOCS3 pathway and may be a potential therapeutic target for breast cancer.

Improving insulin self-injection accuracy in patients with diabetes mellitus through a nursing project.

BACKGROUND: Non-standardized insulin injection has an impact on the efficacy of glucose control. OBJECTIVES: The aim of the study was to explore the effectiveness of a nursing project in improving the insulin self-injection accuracy of diabetes mellitus patients. MATERIAL AND METHODS: A total of 200 type 2 diabetes patients who received insulin therapy with an insulin pen were recruited at the First Affiliated Hospital of Army Medical University (Chongqing, China). Patients were randomly assigned to a control (n = 100) or intervention (n = 100) group. Conventional health education was conducted in the control group, while a nursing project and conventional health education were undertaken in the intervention group. The following parameters were analyzed between the 2 groups: standardized insulin pen use at admission and discharge, glycosylated hemoglobin (HbA1c), time in range (TIR), and adipose hyperplasia incidence rate 6 months after discharge. RESULTS: Concerning standardized insulin self-injection, the intervention group was superior to the control group, and the difference between the 2 groups was statistically significant (p < 0.05). The HbA1c levels (p = 0.000), TIR (p = 0.005) and adipose hyperplasia incidence rate 6 months after discharge (p = 0.000) all improved in the intervention group compared to the control group. CONCLUSIONS: The application of the nursing project effectively improved the efficacy of glucose control in diabetes mellitus patients.