A novel nomogram for identifying candidates for adjuvant chemotherapy in patients with stage IB gastric adenocarcinoma.

BACKGROUND: The purpose of this research was to construct a novel predictive nomogram to identify specific stage IB gastric adenocarcinoma (GAC) populations who could benefit from postoperative adjuvant chemotherapy (ACT). METHOD: Between 2004 and 2015, 1889 stage IB GAC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) program database. Then Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were implemented. Finally, the predictive nomograms were constructed. The methods of area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to validate the clinical effectiveness of the models. RESULTS: Of these patients, 708 cases underwent ACT, while the other 1181 patients didn't receive ACT. After PSM, the patients in the ACT group presented a longer median overall survival (133 vs. 85 months, p = 0.0087). Among the ACT group, 194 (36.0%) patients achieving more prolonged overall survival than 85 months were regarded as the beneficiary population. Then the logistic regression analyses were performed, and age, gender, marital status, primary site, tumor size, and regional nodes examined were included as predicting factors to construct the nomogram. The AUC value was 0.725 in the training cohort and 0.739 in the validation cohort, which demonstrated good discrimination. And calibration curves indicated ideal consistency between the predicted and observed probabilities. Decision curve analysis presented a clinically useful model. Furthermore, the prognostic nomogram predicting 1-, 3-, and 5-year cancer-specific survival presented good predictive ability. CONCLUSION: The benefit nomogram could guide clinicians in decision-making and selecting optimal candidates for ACT among stage IB GAC patients. And the prognostic nomogram presented great prediction ability for these patients.

Associations between apolipoprotein B and bone mineral density: a population-based study.

BACKGROUND: Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers. METHODS: The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship. RESULTS: A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [ß = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [ß = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD. CONCLUSIONS: Our findings suggest that apo B is associated with BMD in a site-specific manner.

Precision Liver Resection: Three-Dimensional Reconstruction Combined with Fluorescence Laparoscopic Imaging.

Liver surgery has entered the era of precision surgery. Therefore, how to optimize the resection of lesions and reduce the unnecessary time of liver ischemia and hypoxia have become the focus. A total of 11 patients who underwent fluorescence laparoscopic liver mass resection and preoperative three-dimensional (3D) reconstruction between August 2018 and July 2020 were evaluated. Liver cirrhosis occurred in 3 patients. The mean intraoperative blood loss was 166.8 ± 105.7 mL. The average length of the operation time was 152.0 ± 45.3 minutes. The average intraoperative hilar occlusion time was 9.3 minutes (except for hilar cholangiocarcinoma). The liver function of all patients, except patients with hilar bile duct carcinoma, returned to the preoperative level at 72 hours, and no serious complications occurred. 3D reconstruction combined with fluorescence laparoscopic imaging is safe and effective for precision liver resection.

Effect of Early and Intensive Rehabilitation after Ischemic Stroke on Functional Recovery of the Lower Limbs: A Pilot, Randomized Trial.

OBJECTIVE: We aimed to develop an early and intense lower extremity training technique using a recumbent cycle ergometer system in patients with acute ischemic stroke. METHODS: This was a pilot, prospective, randomized, controlled study with 2 parallel groups followed for 3 months with blinded assessment of outcomes. Thirty-one eligible patients were randomized to experimental and control groups. To strengthen the motion of the lower extremities within 48 hours after stroke, the control and experimental groups received conventional treatment and additional interventions under a therapist's guidance combined with conventional treatment, respectively. The primary outcome measure was the change in lower extremity motor control from admission to 4 weeks, assessed by the Fugl-Meyer Assessment. Secondary outcomes were the number of days to walking 50 m and the change in the Berg Balance Scale score and Barthel index. The modified Rankin Score was used to assess the overall function and prognosis at 3 months. RESULTS: Fugl-Meyer Assessment and Berg Balance Scale scores and Barthel index increased over time in the experimental group, as did the Berg Balance Scale score and Barthel index in the control group (P < .001). However, Fugl-Meyer Assessment scores in the control group were similar over time (F = 2.303, P = 1.119). Fugl-Meyer Assessment scores in the experimental group were higher than those in the control group after 2 and 4 weeks (P = .084 and .037, respectively). Compared with the control group at 2 weeks or at discharge, the percentage of patients who returned to unassisted walking in the experimental group showed an increasing trend (56.3% versus 26.67%, P = .095), but there was no significant difference between the 2 groups after 3 months (P = .598). The modified Rankin Score at 3 months showed no significant difference between the 2 groups (P > .05). CONCLUSIONS: Our early and intense lower extremity training technique involving a leg cycle ergometer system contributes to the recovery of lower extremity function in patients with acute ischemic stroke. This finding will provide a basis for future investigations on the applicability of the intervention in early lower extremity and walking rehabilitation among individuals with neurological disorder.

Comparative analysis of machine learning-based ultrasound radiomics in predicting malignancy of partially cystic thyroid nodules.

OBJECTIVE: To investigate the application of machine learning (ML) model-based thyroid ultrasound radiomics in the evaluation of malignancy in partially cystic thyroid nodules (PCTNs). METHODS: One hundred and ninety-two patients with 197 nodules PCTNs from January 2020 to December 2020 were retrospectively analyzed. Radiomics features were extracted based on hand-crafted features from the ultrasound images, and machine learning methods were used to build a classification model by radiomics features. The least absolute shrinkage and selection operator regression was applied to select the features of nonzero coefficients from radiomics features. The prediction performance of the established model was mainly evaluated by the area under the curve (AUC) and accuracy, sensitivity, and specificity. RESULTS: Nineteen radiomics features were extracted from the original images for each nodule. Eight ML classifiers were able to differentiate malignancy in PCTNs. The AUC, accuracy, sensitivity, and specificity of k-Nearest Neighbor (KNN) model were 0.909, 82.95%, 83.33%, and 89.90%, respectively, on the test cohort. The comparative result showed statistically equivalent performance for thyroid nodule diagnosis based on image fusion and single image. In addition, the ML-Based ultrasound radiomics system showed a better AUC as compared with ACR TI-RADS model and the ultrasound features model. CONCLUSION: The novel ultrasonic-based ML model has an important clinical value for predicting malignancy in PCTNs. It can provide clinicians with a preoperative non-invasive primary screening method for PCTN diagnosis to avoid unnecessary medical investment and improve treatment outcomes.

A practical approach for finding anti-debugging routines in the Arm-Linux using hardware tracing.

As IoT devices are being widely used, malicious code is increasingly appearing in Linux environments. Sophisticated Linux malware employs various evasive techniques to deter analysis. The embedded trace microcell (ETM) supported by modern Arm CPUs is a suitable hardware tracer for analyzing evasive malware because it is almost artifact-free and has negligible overhead. In this paper, we present an efficient method to automatically find debugger-detection routines using the ETM hardware tracer. The proposed scheme reconstructs the execution flow of the compiled binary code from ETM trace data. In addition, it automatically identifies and patches the debugger-detection routine by comparing two traces (with and without the debugger). The proposed method was implemented using the Ghidra plug-in program, which is one of the most widely used disassemblers. To verify its effectiveness, 15 debugger-detection techniques were investigated in the Arm-Linux environment to determine whether they could be detected. We also confirmed that our implementation works successfully for the popular malicious Mirai malware in Linux. Experiments were further conducted on 423 malware samples collected from the Internet, demonstrating that our implementation works well for real malware samples.

Application of Intraoperative Fluorescence Imaging with Indocyanine Green in the Difficult Gallbladder: A Comparative Study between Indocyanine Green-Guided Fluorescence Cholangiography and Conventional Surgery.

Background: In the difficult gallbladder, the rate of bile duct injury (BDI) remains high. To lessen iatrogenic biliary injury, we attempted to utilize indocyanine green (ICG)-guided fluorescence cholangiography during surgery to illuminate the extrahepatic biliary tract. Materials and Methods: According to admission criteria, 38 patients were diagnosed with difficult gallbladder and underwent percutaneous transhepatic gallbladder drainage (PTGBD). Consecutive patients who underwent ICG-assisted laparoscopic biliary surgery (n = 18, ICG group) or conventional laparoscopic biliary surgery (n = 20, white light [WL group) were enrolled in this study. ICG group received ICG fluorescent cholangiography via PTGBD tube during operation; 16 cases of laparoscopic cholecystectomy (LC) and 2 cases of LC plus laparoscopic common bile duct exploration (LC+LCBDE) were performed by fluorescent laparoscopy. In the WL group, 16 cases of LC, 1 case of laparoscopic subtotal cholecystectomy (LSC), and 3 cases of LC+LCBDE were performed under white light without ICG. Result: The biliary system was successfully established in the ICG group. Compared with the WL group, the anatomy of the Calot's triangle with severe abdominal adhesion or local inflammatory edema was more clearly displayed by fluorescence. Laparoscopic surgery was completed in both groups without conversion to laparotomy. There were no significant differences in surgery-related complications (P = .232) and postoperative hospital stay (P = .074) between the two groups. However, compared with the WL group, the ICG group had less intraoperative blood loss (P = .002) and shorter operation duration (P = .006). Conclusion: ICG fluorescence cholangiography has good clinical application value in the difficult gallbladder, which can avoid iatrogenic BDI, reduce surgery-related complications and intraoperative blood loss, and shorten the duration of surgery.

Anatomic Subsites and Prognosis of Gastric Signet Ring Cell Carcinoma: A SEER Population-Based 1 : 1 Propensity-Matched Study.

BACKGROUND: The dismal prognosis of gastric signet ring cell carcinoma (GSRC) is a global problem. The current study is conducted to comprehensively evaluate clinicopathological features and survival outcomes in GSRC patients stratified by anatomic subsites. Then, predictive nomograms are constructed and validated to improve the effectiveness of personalized management. METHOD: The patients diagnosed with GSRC were recruited from the online SEER database. The influence of anatomic subsites on overall survival (OS) and cancer-specific survival (CSS) was evaluated using multivariate Cox regression and Kaplan-Meier analysis. Then, we employed propensity score matching (PSM) technique to decrease selection bias and balance patients' epidemiological factors. Predictive nomograms were constructed and validated. Sensitivity analysis was performed to validate the conclusion. RESULTS: Multivariate Cox regression demonstrated that the patients with overlapping gastric cancer (OGC) suffered the highest mortality risk for OS (HR, 1.29; 95% CI, 1.23-1.36; P < 0.001) and CSS (HR, 1.33; 95% CI, 1.28-1.37; P < 0.001). Age, TNM stage, tumor localization, tumor size, surgery, and chemotherapy presented a highly significant relationship with OS and CSS. Following subgroup and PSM analysis, OGC patients were confirmed to have the worst OS and CSS. Then, nomograms predicting 6-month, 12-month, and 36-month survival were constructed. The area under the curve (AUC) value in ROC was 0.775 (95% CI, 0.761-0.793) for 6-month survival, 0.789 (95% CI, 0.776-0.801) for 12-month survival, and 0.780 (95% CI, 0.765-0.793) for 36-month survival in the OS group, while in the CSS group, it was 0.771 (95% CI, 0.758-0.790) for 6-month survival, 0.781 (95% CI, 0.770-0.799) for 12-month survival, and 0.773 (95% CI, 0.762-0.790) for 36-month survival. CONCLUSION: We identified anatomic subsites as a predictor of survival in those with GSRC. Patients with OGC suffered the highest mortality risk. The proposed nomograms allowed a relatively accurate survival prediction for GSRC patients.

Circular IGFBP-3 level affected by the gene transfer of different growth hormone isoforms.

To evaluate whether through gene transfer, which growth hormone (GH) isoform can influence the circulation IGFBP-3 level, mice were injected three times with the human cytomegalovirus (CMV) mediated mammalian expression vector encoding different GH isoform gene. Then blood samples were drawn and the ELISA method was used to determine the circulation concentration of IGFBP-3. It was found that the 22 kDa GH gene could increase IGFBP-3 levels to 1.94 microg/ mL whereas 20 kDa GH, 17 kDa GH and 5 kDa GH genes did not play a role in the circulation expression of IGFBP-3.

Nano-biological mesh constructed by astragaloside-IV-induced bone marrow mesenchymal stem cells on PLGA-NPs-SIS can be used for abdominal wall reconstruction.

A combination of stem cells, scaffold materials, nanoparticles (NPs), and physiological factors can be used to engineer a tissue that can replace or improve the function of the damaged tissue. This study was designed to assess whether astragaloside (aS)-IV-activated rat bonemarrow-derived mesenchymal stem cells (BMSCs), seeded on a nano-biological mesh composed of small intestinal submucosa (SIS) modified with poly (D,L-lactide-co-glycolide) NPs (PLGA-NPs-SIS), can promote cell engraftment, proliferation, and mesh incorporation into the tissue upon implantation. aS-IV-induced BMSCs cultured with PLGA-NPs-SIS showed enhanced viability and proliferation as well as reduced apoptosis. Vascular endothelial growth factor, type I and II collagen, and monocyte chemoattractant protein-1 were upregulated, whereas matrix metalloproteinase and interleukin-6 were downregulated in these BMSCs. Pre-seeded BMSCs induced with aS-IV engrafted in a rat abdominal wall defect model showed migratory and proliferative capacities while enhancing vascularity at the musculofascial/graft interface. These findings imply that the nano-biological mesh composed of aS-IV-induced BMSCs seeded on PLGA-NPs-SIS can be used for abdominal wall reconstruction.

Combination of Electronic Choledochoscopy and Holmium Laser Lithotripsy for Complicated Biliary Calculus Treatment: A New Exploration.

The safety and efficacy of the combination of electronic choledochoscopy and holmium laser lithotripsy for complicated bile duct stones were assessed. In total, 20 patients participated in this study, which was conducted between 2012 and 2017. None of the patients were candidates for endoscopic retrograde cholangiopancreatography with stone extraction. Outcome measures included complete stone clearance and complications postprocedure. Mean stone size was 17±5.2 mm (8 to 30 mm) and mean number of stones was 1.7±1.3 (1 to 5). The mean number of laser sessions was 1.3±0.7 (1 to 4). A mean of 1.0 to 1.5 J/20 to 25 Hz was applied during laser lithotripsy sessions with a mean operative time of 67.8±24.8 minutes. The clearance rate of stone was 18/20 (90%). No mortality existed in this study; however, 1 patient developed acute pancreatitis. The combination of holmium laser lithotripsy and electronic choledochoscopy for complicated biliary calculi is safe, reliable, and minimally invasive and has low residual stone rate.

Epigallocatechin-3-gallate confers protection against corticosterone-induced neuron injuries via restoring extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3 kinase/protein kinase B signaling pathways.

Extensive studies suggested epigallocatechin-3-gallate (EGCG) has significant neuroprotection against multiple central neural injuries, but the underlying mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol-3 kinase/ protein kinase B (PI3K/AKT) pathways in EGCG-mediated protection against corticosterone-induced neuron injuries. As an essential stress hormone, corticosterone could induce obvious neurotoxicity in primary hippocampal neurons. Pre-treatment with EGCG ameliorated the corticosterone-induced neuronal injuries; however, it was blocked by pharmacological inhibitors for ERK1/2 (U0126) and PI3K/AKT (LY294002). Furthermore, the results confirmed that EGCG restored the corticosterone-induced decrease of ERK1/2 and PI3K/AKT phosphorylation, and attenuated the corticosterone-induced reduction of peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α) expression and ATP production. Taken together, these findings indicated that EGCG has significant neuroprotection against corticosterone-induced neuron injuries partly via restoring the ERK1/2 and PI3K/AKT signaling pathways as well as the PGC-1α-mediated ATP production.

Inhibition of Dll4/Notch1 pathway promotes angiogenesis of Masquelet's induced membrane in rats.

The Masquelet's induced membrane technique for repairing bone defects has been demonstrated to be a promising treatment strategy. Previous studies have shown that the vessel density of induced membrane is decreased in the late stage of membrane formation, which consequently disrupts the bone healing process. However, relatively little is known about certain mechanisms of vessel degeneration in the induced membrane tissue and whether promotion of angiogenesis in induced membranes can improve bone regeneration. Here, we showed that the Delta-like ligand 4/ Notch homolog 1 (Dll4/Notch1) pathway was relatively activated in the late stage of induced membrane, especially at the subcutaneous site. Then, DAPT, a classical γ-secretase inhibitor, was applied to specifically inhibit Notch1 activation, followed by up-regulation of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31 expression. DAPT-modified induced membranes were further confirmed to contribute to bone regeneration after autogenous bone grafting. Finally, in vitro experiments revealed that knocking down Notch1 contributed to the functional improvement of endothelial progenitor cells (EPCs) and that DAPT-treated induced membrane tissue was more favorable for angiogenesis of EPCs compared with the vehicle group. In conclusion, the present findings demonstrate that Dll4/Notch1 signaling is negatively associated with the vessel density of induced membrane. Pharmacological inhibition of Notch1 attenuated the vessel degeneration of induced membrane both in vitro and in vivo, which consequently improved bone formation at the bone defect site and graft resorption at the subcutaneous site.

Involvement of PKCα and ERK1/2 signaling pathways in EGCG's protection against stress-induced neural injuries in Wistar rats.

Stress-induced neural injuries are closely linked to the pathogenesis of various neuropsychiatric disorders and psychosomatic diseases. We and others have previously demonstrated certain protective effects of epigallocatechin-3-gallate (EGCG) in stress-induced cerebral impairments, but the underlying protective mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of PKCα and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in EGCG-mediated protection against restraint stress-induced neural injuries in rats. In both open-field and step-through behavioral tests, the restraint stress-induced neuronal impairments were significantly ameliorated by administration of EGCG or green tea polyphenols (GTPs), which was associated with a partial restoration of normal plasma glucocorticoid, dopamine and serotonin levels. Furthermore, the stress-induced decrease of PKCα and ERK1/2 expression and phosphorylation was significantly attenuated by EGCG and to a less extent by GTP administration. Additionally, EGCG supplementation restored the production of adenosine triphosphate (ATP) and the expression of a key regulator of cellular energy metabolism, the peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), in stressed animals. In conclusion, PKCα and ERK1/2 signaling pathways as well as PGC-1α-mediated ATP production might be involved in EGCG-mediated protection against stress-induced neural injuries.

Influencing Factors of Knowledge, Attitude, and Practice regarding Medical Nutrition Therapy in Patients with Diabetes: A National Cross-Sectional Study in Urban China.

To investigate the knowledge-attitude-practice (KAP) score in diabetes patients living in urban China regarding Medical Nutrition Therapy (MNT) and explore the influencing factors, this national survey recruited diabetes and prediabetes patients in 40 hospitals across 26 provinces in China. A self-designed questionnaire was used to collect the data and assess the knowledge, attitude, and practice regarding MNT. Logistic regression was used to explore the factor influencing KAP scores. A total of 6441 diabetes patients (mean age: 60.02 ± 13.14 years) completed this survey. The mean glycosylated hemoglobin (HbA1c) level was 8.12 ± 2.12%, and the control rate of HbA1c (HbA1c < 7.0%) was 38.92%. Of the total, 53.56% had received MNT education. Over half of the patients had a poor total KAP score as well as poor K, A, and P scores. Patients with higher KAP scores had higher control rate of HbA1c (P < 0.05) but lower levels of fasting plasma glucose (FPG) and 2-hour postprandial blood glucose (2h-PG). Gender, occupation, residence, education level, and MNT education could influence the KAP scores (P < 0.05). This study showed that diabetes patients in urban China generally had poor understandings and practices related to MNT. Patients with higher KAP scores exhibited better control of blood glucose.

Enhancement of the effects of gemcitabine against pancreatic cancer by oridonin via the mitochondrial caspase-dependent signaling pathway.

Gemcitabine is a first­line chemotherapeutic agent used in the treatment of pancreatic cancer; however resistance of the disease to the drug often develops over time. Agents that can either enhance the effects of gemcitabine, or help to overcome the chemoresistance to the drug are needed for the successful treatment of pancreatic cancer. Oridonin is one such agent which is safe and multi­targeted and has previously been shown to induce apoptosis in other tumor cells, through mitochondrial signaling pathways. The aims of the present study were to evaluate whether oridonin may enhance the effects of gemcitabine on pancreatic cancer in vitro and to investigate the possible mechanisms of this enhancement. In vitro studies have previously shown that oridonin can inhibit the proliferation of the Panc­1 pancreatic cancer cell line, and potentiate gemcitabine­induced apoptosis, which was shown to be associated with cell cycle arrest in the G1 phase. Western blot and quantitative polymerase chain reaction analyses demonstrated that the expression levels of the anti­apoptotic gene Bcl­2 and the Bcl­2/Bax ratio in the oridonin and the oridonin plus gemcitabine groups were significantly downregulated as compared with the gemcitabine treatment and control groups. The expression levels of pro­apoptotic genes Bax, cytochrome c (cyt c), and caspase­3 and ­9 in the oridonin and the combination groups were significantly upregulated as compared with the other two groups. The results suggested that oridonin improved the anti­tumor effects of gemcitabine through the enhancement of gemcitabine­induced apoptosis.This mechanism may be through the downregulation of Bcl­2 expression and the upregulation of Bax expression, resulting in the reduction of the Bcl­2/Bax ratio. These effects may promote the release of cyt c from the mitochondria into the cytoplasm thus triggering the mitochondrial apoptosis signaling pathway. Furthermore, caspase­3 and ­9 were shown to be activated as a result of the induction of apoptosis.