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Aims: This work was designed to identify the subgroup of advanced hepatocellular carcinoma (HCC) patients for whom treatments containing immune checkpoint blockers (ICBs) were most effective. Materials & methods: A meta-analysis was performed to explore the subgroup population with the greatest benefit of treatments containing ICBs. Results: A total of 2228 patients from four randomized control trials were included. Treatments containing ICBs had better overall survival, progression-free survival and higher objective response rate over treatment without ICBs. Subgroup analysis revealed that treatments containing ICBs were highly effective in improving the overall survival of males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients. Conclusion: Treatments containing ICBs are more effective for males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients.

Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69–5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83–14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93–2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02–3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44–1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45–1.08). Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC.

The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs. The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS). Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40–0.56; PFS:HR = 0.39, 95%CI:0.33–0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82–2.89; PFS:HR = 2.34, 95%CI = 1.69–3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41–0.62; PFS:HR = 0.39, 95%CI:0.30–0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16–0.71; PFS:HR = 0.22, 95%CI:0.10–0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment. AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy. The review was not registered.

Objective: This meta-analysis was designed to explore the association between the systemic immune–inflammation index (SII) and the therapeutic effect of immune checkpoint inhibitors. Materials & methods: The authors retrieved relevant studies published before May 25, 2022. Hazard ratio (HR) with 95% CI was used to evaluate the relationship between SII and overall survival (OS) and progression-free survival (PFS). Results: 14 articles comprising 2721 patients were included in this study. The pooled results proved that high SII levels were closely related to poor prognosis in cancer patients receiving immune checkpoint inhibitors (OS HR = 2.40; 95% CI: 2.04–2.82; PFS HR = 1.57; 95% CI: 1.33–1.86) and that an SII value of 750 was appropriate as a cut-off value (OS HR = 2.20; 95% CI: 1.83–2.63; PFS HR = 1.54; 95% CI: 1.33–1.80). Conclusion: High SII levels (>750) may be an indicator of worse OS and PFS in cancer patients treated with immune checkpoint inhibitors.

Background The RET gene, which is frequently mutated across many types of cancer, has been proven to be critically involved in tumorigenesis and tumor development, while its precise contribution to immune checkpoint inhibitors (ICIs) therapy remains to be elucidated. The present research aims to investigate the association between RET mutations and the efficiency of ICIs therapy.Method We analyzed the role of RET mutations in predicting the prognosis of patient receiving ICIs therapy in the discovery cohort and validated it in the validation cohort. Then, multi-omics data from TCGA pan-cancer cohort was employed to propose the association between RET mutations and tumor inflamed anti-tumor immune response and tumor antigenicity.Results Our study revealed that RET mutation is associated with better clinical outcomes for ICIs therapy in 606 cases across five types of cancer, including elevated response rate, longer PFS and OS. Multivariate analysis showed that RET mutation could independently predict the prognosis of ICIs-treated patients after adjusting cancer types. The predictive value of RET status for the OS of patients treated with ICI immunotherapy was further validated in the validation cohort (n = 1683). Subgroup analysis suggested that only the monotherapy group showed significant differences in OS and PFS between RET- wildtype tumors and RET- mutant tumors. Multi-omics data analysis revealed potential anti-tumor immunity mechanisms of RET mutations, suggesting that RET-mutant tumors have enhanced immunogenicity, higher expression of immune checkpoints, chemokines, and immune cell infiltration than RET-wildtype tumors, potentially indicating a more favorable response to immunotherapy.Conclusions RET mutation may be a predictive biomarker of enhanced response to ICIs therapy. Extensive molecular mechanism investigation and prospective studies are needed in the future.

Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in various types of previously untreatable malignancies, while limited evidence is available on the management of hepatitis B virus (HBV) in patients undergoing immunotherapy. We systematically reviewed data concerning challenges of hepatic adverse events including HBV reactivation and hepatitis in patients with chronic HBV infection undergoing immunotherapy.A systematic search was conducted in Medline, web of science, Embase and Cochrane library up to May 31, 2022. Studies reporting the safety profile of ICIs in patients with HBV infection were eligible. Meta-analyses were conducted to generate odds ratios (ORs) with 95% confidence intervals (CIs).A total of 13 studies including 2561 patients were included for meta-analysis. The overall incidence rates of HBV reactivation in patients with chronic HBV infection and past HBV infection were 1.0% (95% CI 0-3%) and 0% (95% CI 0-0%), respectively. Among patients with chronic HBV infection, the incidence rates of HBV reactivation were 1.0% (95% CI 0-2%) and 10.0% (95% CI 4-18%) for patients with and without antiviral prophylaxis, respectively. Patients with chronic HBV infection were at a higher risk of HBV reactivation compared with those with past HBV infection [OR = 8.69, 95% CI (2.16-34.99)]. Antiviral prophylaxis significantly reduced the risk of HBV reactivation [OR = 0.12, 95% CI (0.02-0.67)] and HBV-associated hepatitis [OR = 0.05, 95% CI (0.01-0.28)] in patients with chronic HBV infection.Prophylactic antiviral therapy should be administered to patients with chronic HBV infection undergoing anticancer immunotherapy. Patients with past HBV infection are at lower risk of HBV reactivation compared with those with chronic HBV infection, they could be initiated with antiviral prophylaxis or monitored with the intent of on-demand antiviral therapy.

Although permanent magnet couplings (PMCs) have been under research for many years and have found successful industrial applications, this is still a technology under development. Accurate parameter determination is of significance for performance analysis and critical decisions on PMC design. However, the determination can often lead to an unacceptable increase in computation, especially when the finite element (FE) method is used. The study aims to develop an FE model that is used for the structural design of a standard-disc type PMC for optimal torque. For the quick and accurate design, an integration optimal solution of the response surface methodology (RSM) and the Taguchi’s method was proposed. To verify the simulation, a series of experimental investigations were conducted on a self-developed testing platform. Furthermore, for a minimum set of FE analyses (FEA), a quantitative indicator called contribution rate, which can reflect effect level of structure parameters on the torque, was given based on the Taguchi method. Apart from this, the orthogonal matrix was used for the reduction of the FE calculation. Based on the contribution rate, the response surface methodology was adopted for the optimal torque determination with no increase in the PM volume. According to the optimization results, a fitting formula, which considers the contribution rates of the optimization variables, was presented. The results suggest that the FE simulations agree very well with the experiments, and the fitting formula can be used in the PMC design.

To evaluate and predict liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), several non-invasive scoring systems were built and widely used in the progress of diagnosis and treatment, which showed great diagnostic efficiency, such as aspartate aminotransferase to platelet ratio index, fibrosis-4 index, body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes score and NAFLD fibrosis score. Since the new concept of metabolic associated fatty liver disease (MAFLD) was proposed, the clinical application value of the non-invasive scoring systems mentioned above has not been assessed in MAFLD. The evaluation of the diagnostic performance of these non-invasive scoring systems will provide references for clinicians in the diagnosis of MAFLD.

Background: Combination immunotherapy have gradually become the mainstay of systematic therapy for hepatocellular carcinoma (HCC), however, prescribing immunotherapies perioperatively has the potential to reduce tumor activity, while increasing the resection rate and improving prognoses. This study investigated the efficacy and safety of preoperative combined immunotherapies for patients with initially unresectable HCC. Methods:This retrospective, real-world study involved patients with initially unresectable HCC receiving combined immunotherapies based on PD-1/L1 blockade before surgery. Tumor treatment responses, pathological manifestations in postoperative specimens and overall survival (OS) were evaluated. Treatment related adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Results: The study consecutively included 54 initially unresectable HCC patients and 34 patients were evaluated the safety, efficacy and possibility of subsequent radical surgery. Among these patients with surgical resection, 57.1% (n=8) receiving combination immunotherapy before surgery achieved a partial response (PR), which highlighted a 30% reduction in tumor size. Pathological evaluation of postoperative specimens confirmed that 21.4% (n=3) achieved complete responses. 78.6% (n=11) achieved partial responses. 28.6% (n=4) encountered grade 3 or 4 AEs out of 14 patients. The main AEs included fatigue (n=11; 78.6%), leukocytopenia (n=8; 57.1%,) and aspartate aminotransferase (AST) elevation (n=6; 42.9%). Conclusions: After the application of combination immunotherapy, patients should be comprehensively evaluated whether they meet the criteria for surgical resection. This surgical resection following by combination immunotherapy might effectively control tumor progression and could improve the prognosis at least for some patients with initially unresectable HCC.

The introduction of immune checkpoint inhibitors (ICIs) has reshaped the therapy of hepatocellular carcinoma (HCC). ICIs are a novel therapy with frequent adverse events (AEs), including treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). However, no comprehensive overview of the toxicity spectrum of ICIs in HCC patients has been provided. Electronic databases were searched to identify eligible studies. A meta-analysis of the incidence rate of AEs in HCC patients treated with ICIs was performed. Lastly, the prognostic value of irAEs in HCC patients treated with ICIs was verified. Forty-seven studies with 6472 participations met the inclusion criteria. The pooled all-grade trAEs incidence rate was 83.4% (95% confidence interval [95% CI] 77.0-89.1%), ≥ grade 3 trAEs incidence rate was 33.0% (95% CI 26.9-39.5%), all-grade irAEs incidence rate was 34% (95% CI 22-47%), and ≥ grade 3 irAEs incidence rate was 9% (95% CI 5-14%). Aspartate aminotransferase (AST) increase (38%, 95% CI 35-40%) is the most common trAEs. Fatigue (14%, 95% CI 7-23%) is the most common irAEs. The pooled results also showed that 18.8% (95% CI 13.2-25.2%) of patients required systemic steroid therapy due to AEs, while 6.6% (95% CI 4.6-9.0%) of patients withdrew from treatment due to AEs. Additionally, patients experiencing irAEs may have a better progression-free survival (PFS) (multivariate analysis: hazard ratio [HR] = 0.41, 95% CI 0.27-0.61, I

• Background The double-lumen tube (DLT) is an essential equipment for thoracic anesthesia and the precise position of DLT placement is particularly important for anesthesia and surgery. However, the incidence of DLT malposition remains high and it leads to lung isolation failure and hypoxemia during one-lung ventilation. This trial aims to explore the clinical application and efficacy of intubation in the lateral position under general anesthesia induction to reduce the incidence of DLT malposition in patients undergoing unilateral video-assisted thoracic surgery (VATS). • Methods In this prospective, randomized, controlled trial, we will recruit 108 patients, aged 18–80 years, scheduled for elective unilateral VATS with DLT intubation under general anesthesia, and they will be randomly assigned to two groups: a lateral DLT intubation group (group L) and a conventional supine DLT intubation group (group C). The left-sided DLT will be used to intubate in patients of both groups. The position of DLT will be confirmed and adjusted by using the fiberoptic bronchoscopy (FOB). The primary outcome is the incidence of DLT malposition observed via the FOB, and the secondary outcomes include the time of intubation, the frequency and duration of re-adjustments of DLT placement under FOB, whether to re-intubation, intraoperative vital signs and postoperative recovery. • Discussion Accurate DLT positioning is particularly important in thoracic surgery, but the incidence of DLT malposition is still high in the present thoracic anesthesia. This trial aims to investigate whether lateral DLT intubation can reduce the incidence of DLT malposition, with more stable intraoperative vital signs and fewer postoperative complications. Trial registration: Study protocol registered at Chinese Clinical Trial Registry with ChiCTR2200060794 on June 11, 2022.

Most patients with hepatocellular carcinoma (HCC) have underlying cirrhosis and a compromised liver function. Immune checkpoint inhibitors (ICIs) have emerged as an important approach for HCC treatment. The purpose of our study was to explore the prognostic significance of liver function in HCC patients receiving ICIs.Hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the relationship between liver function and overall survival (OS)/progression-free survival (PFS).41 articles with 4483 patients with HCC were included. The pooled results revealed that either Child-Pugh score (OS:HR = 2.01,95 %CI:1.69-2.38; PFS:HR = 1.39,95 %CI:1.15-1.68) or albumin-bilirubin (ALBI) score (OS:HR = 2.04,95 %CI:1.55-2.69; PFS:HR = 1.42,95 %CI:1.21-1.67) can predict the patient prognosis. The Child-Pugh score has some degree of subjectivity, and the ALBI score can better stratify patients. Therefore, the ALBI score was used to evaluate patients' liver function and determine treatment options. Further subgroup analysis found that the results of prospective studies were statistically significant only for the ALBI score with regards to OS (HR = 1.69,95 %CI:1.26-2.26). Meanwhile, the effect of liver function on the efficacy of ICIs in the large-sample studies was not as obvious as that in small-sample studies. Moreover, the incidence of adverse events did not significantly increase in patients with impaired liver function.Poor liver function is associated with a poor prognosis in patients with HCC receiving ICIs. The ALBI score is simpler and reliable for patient stratification than the Child-Pugh score. Although the survival time of patients with impaired liver function may be relatively short, ICIs still have great potential for therapeutic applications.

Ultrasonic assisted inner diameter machining is a common slicing method for hard and brittle materials, and the sawing force is the main factor affecting the quality of workpiece surface and tool life, so to explore the sawing force is to research the sawing process. An improved model of normal sawing force is proposed in this paper with spherical abrasive particles. A series of sawing experiments were carried out with alumina ceramics (99%) as typical hard and brittle materials to verify the correctness of the theoretical model and discuss the influence of machining parameters on the normal sawing force. In the experiment, the results show that the average error and the variance of the improved normal sawing force model are decreased obviously compared with the average error and the variance of the regular tetrahedral abrasive normal sawing force model. So, the model proposed in this paper is more accurate. The establishment of this model has guiding significance for the selection of process parameters, the improvement of processing efficiency and quality in subsequent actual production and processing.

The purpose of the present study was to evaluate the effect of direct-acting antivirals (DAAs) therapy on the clinical outcomes of hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC).We searched multiple electronic databases from database inception to June 14, 2021. Meta-analyses were performed separately for HCC recurrence and overall survival (OS).A total of 23 studies were identified for the primary analysis. Compared with no intervention, pooled data showed significant benefit from DAAs therapy in reducing recurrence (adjusted HR = 0.55, 95% CI 0.41-0.74, P 0.001; IDAAs therapy can prevent recurrence and improve OS of HCV-related HCC patients, especially for patients with SVR. Further prospective randomized controlled trial is warranted to validate these results.

γ-aminobutyric acid is a nonprotein amino acid that accumulates in plants under stress. Abscisic acid is important for stress regulation via modulation of γ-aminobutyric acid function. Our results show that the expression of glutamate decarboxylase but not diamine oxidase gene is upregulated in germinating soybean treating treated with exogenous abscisic acid. There was a concomitant increase in glutamate decarboxylase and diamine oxidase activities and putrescine and spermine contents with a decrease in glutamate. These changes were abrogated by fluridone, an inhibitor of abscisic acid synthesis. In conclusion, abscisic acid treatment increases γ-aminobutyric acid accumulation by upregulating diamine oxidase gene expression and activation of glutamate decarboxylase and diamine oxidase activity in germinating soybean under hypoxia-salt stress.

The magnetic spring is a practical element to isolate external vibration to instruments in ultra-precision manufacturing and ultra-precision testing. Accurate magnetic force and stiffness models are necessary to analyze and optimize the design of magnetic spring isolators. Thus, this study proposes an accurate magnetic force and stiffness model to design and analyze a variable stiffness nonlinear magnetic spring (VSNMS) considering the permanent magnet’s (PM’s) relative permeability, positions, sizes, and magnetic properties. Firstly, the VSNMS’s structure is designed and introduced, and its magnetic force and stiffness models are derived. Secondly, the established model is validated by comparison with the numerical simulation. Thirdly, the VSNMS prototype is fabricated, and then tested through an electronic universal testing machine. The model has the advantage of high accuracy, high efficiency, and ease of use compared with numerical simulations and experimental tests. Furthermore, parametric studies are conducted to learn the effect of PMs’ sizes, positions, and magnetic properties on VSNMS’s magnetic force and stiffness characteristics. Finally, the optimized structural size parameters of VSNMS are obtained using the derived model and the interior-point algorithm. As a result, the established model contributes to the analysis and optimal design of VSNMS, supporting the design of magnetic spring isolators in ultra-precision applications.

BACKGROUND AND AIM Salivary characteristics are altered in gastrointestinal diseases and related to oral taste disorder. However, specific salivary biochemical characteristics and their relationships with oral taste disturbances in chronic non-atrophy gastritis (CNAG) remain uncertain. METHODS Seventy patients with CNAG and 70 subjects in healthy control group (HCG) were enrolled in our study. The levels of salivary flow rate (SFR), pH, salivary α-amylase (sAA) activity, total protein density (TPD), chloride concentration, and calcium concentration were determined before and after citric acid stimulation and compared between CNAG with and without oral taste disturbances. RESULTS Average body mass index (BMI) of CNAG (17.75 ± 2.08) was lower than that of HCG (21.96 ± 1.72, P

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, having a significantly poor prognosis and no sufficiently efficient treatments. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided new therapeutic approaches for HCC patients. Nevertheless, most patients with HCC do not benefit from immunotherapy. Exosomes are biologically active lipid bilayer nano-sized vesicles ranging in size from 30 to 150 nm and can be secreted by almost any cell. In the HCC tumor microenvironment (TME), numerous cells are involved in tumor progression, and exosomes—derived from tumor cells and immune cells—exhibit unique composition profiles and act as intercellular communicators by transporting various substances. Showing the dual characteristics of tumor promotion and suppression, exosomes exert multiple functions in shaping tumor immune responses in the crosstalk between tumor cells and surrounding immune cells, mediating immunotherapy resistance by affecting the PD-1/PD-L1 axis or the anti-tumor function of immune cells in the TME. Targeting exosomes or the application of exosomes as therapies is involved in many aspects of HCC immunotherapies (e.g., ICIs, tumor vaccines, and adoptive cell therapy) and may substantially enhance their efficacy. In this review, we discuss the impact of exosomes on the HCC TME and comprehensively summarize the role of exosomes in immunotherapy resistance and therapeutic application. We also discuss the potential of exosomes as biomarkers for predicting the efficacy of immunotherapy to help clinicians in identifying HCC patients who are amenable to immunotherapies.

Background Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte injury, which induced by metabolic disorder. Nowadays, there is still a lack of drugs for the treatment of DCM. Growth differentiation factor 11 (GDF11) is a novel member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in DCM remain largely unknown. Methods In this study, we sought to determine whether GDF11 could prevent DCM. The mouse model of diabetes was established by administering a high-fat diet and intraperitoneal injecting streptozotocin. After that, intramyocardial injection of an adeno-associated virus carrying GDF11 gene was used to achieve myocardium-specific overexpression. Results Our data showed that GDF11 overexpression remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression was observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were also eliminated by SIRT1 depletion. Conclusion Our results demonstrated for the first time that GDF11 protected against DCM by regulating SIRT1 signaling pathway, and GDF11 had the potential to become a novel target for reversing cardiac dysfunction in diabetic patients.

The etiology of gallstones at different anatomical locations may be varied. However, it has not been well studied about the prevalence of gallstones by anatomical locations and their associated factors in China.We used the data set from preventive health screening centers covering all provinces in mainland China except for Tibet, and a total of 10,937,993 adults were included, who received abdominal ultrasonography in 2017. We analyzed the prevalence of gallstones classified by anatomical locations, including gallbladder (GB) stones, intrahepatic bile duct (IHD) stones, and extrahepatic bile duct (EHD) stones. Further, their associated factors were investigated using a logistic regression model with body mass index (BMI), fasting glucose, total triglyceride, and previous cholecystectomy, with covariates of age and sex.The age- and gender-standardized prevalence (AGS-prevalence) of gallstone diseases was 5.13% (95% CI: 5.11-5.14%). GB, IHD, and EHD stones accounted for 76.3%, 24.3%, and 0.2% of all gallstone cases (concomitant cases were present). GB, IHD, and EHD gallstones presented different patterns by the age, gender, geographic and metabolic factors. Overall, the age-standardized prevalence was higher in women than that in men (5.41% vs. 4.85%, P0.001). The gender standardized prevalence of all gallstone subtypes apparently increased with age (P0.001), especially for GB stones from 1.05% (age 18-30) to 11.6% (age ≥70) (P0.001). There was a marked geographic variation with AGS-prevalence ranging from 3.00% to 8.86% among different provinces. Noticeably, higher BMI, fasting glucose level, or total triglyceride level was associated with a higher prevalence of overall gallstones and GB stones (OR1), but associated with a lower prevalence of IHD and EHD stones.The prevalence of gallstones in China largely varied in its anatomical location, demographic factors, geographic location, and metabolic factors, suggesting that the etiology of each subtype may be different. Further investigation should be conducted.

A novel numerical piston-type wave-maker toolbox for the OpenFOAM is developed and demonstrated in this paper. This toolbox is implemented in C++ for improving the solutions of nonlinear wave problems in the field of hydrodynamics. As a toolbox that generates waves using the piston-type method only, it contains several frequently used functions, including the generation and the absorption of waves of various forms, an active absorption system and the porous media flow. Furthermore, to illustrate the operability of the toolbox, some validations and applications are presented, including the regular waves, the irregular waves, and the solitary waves. In each case, a satisfactory agreement is obtained in comparison with the published experimental or theoretical results,so this toolbox may be applied with a considerable confidence.

Aberrant expression of microRNAs (miRNAs) plays an important role in gastric cancer (GC) development. miR-93-5p has shown opposing functions in different types of cancers, but the exact expression pattern and molecular mechanism of miR-93-5p in GC development remain to be elucidated. Here, we reported that miR-93-5p expression was increased in GC tissues compared with the adjacent normal tissues and that its overexpression was correlated with distant metastasis and poor survival in GC patients. miR-93-5p knockdown inhibited the migration, invasion and proliferation of GC cells in vitro and in vivo, while its overexpression displayed an opposite result. Using an mRNA microarray, we found that miR-93-5p significantly downregulated IFNAR1 expression in GC cells, which was further identified as a direct target of miR-93-5p. IFNAR1 knockdown promoted GC cell migration and invasion, but its restoration could rescue GC cell migration and invasion induced by miR-93-5p overexpression. Moreover, miR-93-5p-IFNAR1 axis increased MMP9 expression via STAT3 pathway in GC cells. Taken together, we reveal that miR-93-5p overexpression is associated with the poor survival of GC patients and miR-93-5p-IFNAR1 axis promotes GC metastasis through activation of STAT3 pathway.

Currently, most of the traditional flow pattern recognition methods are based on the features of differential pressure signal, and the verification data is majorly derived from the horizontal or almost horizontal pipes. This paper proposes a new method that combines the probability density function (PDF) of the liquid holdup signal and the support vector machine (SVM). Results demonstrate the capability of the proposed algorithm to effectively recognize the stratified flow, bubble flow, slug flow, and severe slug flow and eliminate subjective factors.

In vertical gas-liquid two-phase annular flow, the radial evolution of droplets in the gas core plays a key role in affecting the characteristic of gas carrying liquids. In this paper, the droplets size and velocity at 11 radial positions were measured with the phase Doppler anemometry and then analyzed based on the recognition method of droplet role to figure out the radial evolution characteristics of droplets flow rate, size, velocity, and momentum. The results show that the droplet quantity flow rate decreases with the entrained droplets moving from the liquid film-gas core interface to the centerline, due to the fact that the droplet coalescence has a greater effect than the droplet breakup. The proportion of small droplets decreases while the proportion of relatively large droplets increases. The overall distribution characteristics of droplet diameter remain unchanged. The overall distribution characteristics of droplet axial velocity, radial velocity, and velocity size remain unchanged, although the droplets undergo the process of axial acceleration and radial deceleration during the radial migration. The distribution of droplet momentum varies greatly in the process of droplet radial migration. The contribution of small droplets to the total droplet momentum gradually decreases, while the contribution of large droplets to the total droplet momentum gradually increases. Although the number of large droplets is small, their contribution to the total droplet momentum cannot be neglected.

Colon cancer is one of the most common malignancies of the digestive system. Although more effective therapeutic strategies have been developed in the last decades, there is still a great clinical need to explore new treatment regimens for colon cancer due to the undesirable prognosis. In the present study, we investigated the anticancer activity of resveratrol (Res) in human colon cancer cells, and the possible mechanism underlying this effect. We employed crystal violet staining, flow cytometry and western blotting to test the antiproliferation- and apoptosis-inducing effects of Res in LoVo cells. A xenograft tumor model was also introduced to confirm the in vivo anticancer effect of Res. Using PCR, western blotting, a recombinant adenovirus and a specific inhibitor of p38 MAPK or bone morphogenetic protein receptor (BMPR) to explore the possible molecular mechanisms. We found that Res markedly inhibited the proliferation and promoted the apoptosis of LoVo cells, and suppressed the in vivo tumor growth of colon cancer. Res substantially upregulated the expression of bone morphogenetic protein 9 (BMP9). Exogenous expression of BMP9 enhanced the anticancer effect of Res in LoVo cells, while BMP9 knockdown partly reduced this activity. Res increased the activation of p38 MAPK, which was enhanced by the exogenous expression of BMP9. The anticancer activity of Res, or Res combined with BMP9, was reduced partly by the p38 MAPK inhibitor. The BMPR inhibitor almost abolished the Res-induced activation of p38 MAPK, and attenuated the antiproliferative effect of Res in the LoVo cells. Our findings strongly suggest that the anticancer effect of Res in human colon cancer cells may be partly mediated by upregulation of BMP9 to activate p38 MAPK in a BMPR-dependent manner.