Deep Learning-Based Simultaneous Temperature- and Curvature-Sensitive Scatterplot Recognition.

Since light propagation in a multimode fiber (MMF) exhibits visually random and complex scattering patterns due to external interference, this study numerically models temperature and curvature through the finite element method in order to understand the complex interactions between the inputs and outputs of an optical fiber under conditions of temperature and curvature interference. The systematic analysis of the fiber's refractive index and bending loss characteristics determined its critical bending radius to be 15 mm. The temperature speckle atlas is plotted to reflect varying bending radii. An optimal end-to-end residual neural network model capable of automatically extracting highly similar scattering features is proposed and validated for the purpose of identifying temperature and curvature scattering maps of MMFs. The viability of the proposed scheme is tested through numerical simulations and experiments, the results of which demonstrate the effectiveness and robustness of the optimized network model.

Assessing the potential spray drift of a six-rotor unmanned aerial vehicle sprayer using a test bench and airborne drift collectors under low wind velocities: impact of atomization characteristics and application parameters.

BACKGROUND: The unmanned aerial spraying systems (UASS) have gained widespread use for plant protection in recent years. However, spray drift from UASS is a major concern when controlling weeds over large areas and warrants a thorough investigation. This study examined the atomization characteristics of the herbicide florpyrauxifen-benzyl under downwash airflow using a UASS spray test platform. Potential spray drift was assessed using a test bench (TB) and airborne drift collectors (ADCs) in the field under low wind speeds (<1 m s-1). RESULTS: Atomization characteristics were significantly affected by the spray liquid, adjuvant, nozzle type and spray pressure. The addition of an adjuvant reduced the liquid sheet length, improved physicochemical properties and increased droplet size under the downwash airflow field. Drift evaluation in the field using the TB revealed that sediment spray drift predominantly occurred from the middle to the entire length of the device when fine-to-medium droplets were produced after the sprayer passed. ADC assessment found that higher flight altitudes and finer droplets resulted in higher drift values, whereas the addition of an adjuvant and the use of an air-induction nozzle reduced drift <3 m aboveground. CONCLUSION: The combination of using TB in the target area and ADCs in the off-target area as an alternative method to determine residual droplets in the current airflow provided valuable insights into airborne drift assessment for UASS. © 2024 Society of Chemical Industry.

Consensus-Agent Deep Reinforcement Learning for Face Aging.

Face aging tasks aim to simulate changes in the appearance of faces over time. However, due to the lack of data on different ages under the same identity, existing models are commonly trained using mapping between age groups. This makes it difficult for most existing aging methods to accurately capture the correspondence between individual identities and aging features, leading to generating faces that do not match the real aging appearance. In this paper, we re-annotate the CACD2000 dataset and propose a consensus-agent deep reinforcement learning method to solve the aforementioned problem. Specifically, we define two agents, the aging process agent and the aging personalization agent, and model the task of matching aging features as a Markov decision process. The aging process agent simulates the aging process of an individual, while the aging personalization agent calculates the difference between the aging appearance of an individual and the average aging appearance. The two agents iteratively adjust the matching degree between the target aging feature and the current identity through a form of synergistic cooperation. Extensive experimental results on four face aging datasets show that our model achieves convincing performance compared to the current state-of-the-art methods.

Laparoscopic orchidopexy for the treatment of cryptorchidism in adults: a description of the technique and outcomes.

BACKGROUND: There are few studies on cryptorchidism in adults, and its treatment is still controversial. METHODS: To summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed. RESULTS: All testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach's triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery. CONCLUSION: Our study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient's reproductive hormone secretion function.

SurgNet: Self-Supervised Pretraining With Semantic Consistency for Vessel and Instrument Segmentation in Surgical Images.

Blood vessel and surgical instrument segmentation is a fundamental technique for robot-assisted surgical navigation. Despite the significant progress in natural image segmentation, surgical image-based vessel and instrument segmentation are rarely studied. In this work, we propose a novel self-supervised pretraining method (SurgNet) that can effectively learn representative vessel and instrument features from unlabeled surgical images. As a result, it allows for precise and efficient segmentation of vessels and instruments with only a small amount of labeled data. Specifically, we first construct a region adjacency graph (RAG) based on local semantic consistency in unlabeled surgical images and use it as a self-supervision signal for pseudo-mask segmentation. We then use the pseudo-mask to perform guided masked image modeling (GMIM) to learn representations that integrate structural information of intraoperative objectives more effectively. Our pretrained model, paired with various segmentation methods, can be applied to perform vessel and instrument segmentation accurately using limited labeled data for fine-tuning. We build an Intraoperative Vessel and Instrument Segmentation (IVIS) dataset, comprised of ~3 million unlabeled images and over 4,000 labeled images with manual vessel and instrument annotations to evaluate the effectiveness of our self-supervised pretraining method. We also evaluated the generalizability of our method to similar tasks using two public datasets. The results demonstrate that our approach outperforms the current state-of-the-art (SOTA) self-supervised representation learning methods in various surgical image segmentation tasks.

Research trends and hotspots in exercise rehabilitation for coronary heart disease: A bibliometric analysis.

Exercise rehabilitation can improve the prognosis of patients with coronary heart disease. However, a bibliometric analysis of the global exercise rehabilitation for coronary heart disease (CHD) research topic is lacking. This study investigated the development trends and research hotspots in the field of coronary heart disease and exercise rehabilitation. CiteSpace software was used to analyze the literature on exercise therapy for CHD in the Web of Science Core Collection database. We analyzed the data of countries/institutions, journals, authors, keywords, and cited references. A total of 3485 peer-reviewed papers were found, and the number of publications on the topic has steadily increased. The most productive country is the USA (1125), followed by China (477) and England (399). The top 3 active academic institutions are Research Libraries UK (RLUK) (236), Harvard University (152), and the University of California System (118). The most commonly cited journals are Circulation (2596), The most commonly cited references are "Exercise-based cardiac rehabilitation for coronary heart disease" (75), Lavie CJ had published the most papers (48). World Health Organization was the most influential author (334 citations). The research frontier trends in this field are body composition, participation, and function. Research on the effects of physical activity or exercise on patients with CHD is a focus of continuous exploration in this field. This study provides a new scientific perspective for exercise rehabilitation and CHD research and gives researchers valuable information for detecting the current research status, hotspots, and emerging trends for further research.

The theoretical model and sinusoidal optimization strategy for oscillating shear valve type continuous waves generator.

Continuous-wave mud generator is widely adopted for real-time downhole data transmission of deep wells in the oil industry. There have been many studies on rotor structure optimization of continuous rotary valve tools but few studies on the different optimization mechanisms of oscillating shear valve tools. In this paper, a theoretical model of pressure wave generation for oscillating shear valve tools was presented, and the reason for the non-sinusoidal waveform was analyzed theoretically for the first time. A series of rotor rotation strategies were proposed to improve the sinusoidal properties of pressure waves without changing the mechanical structure of the rotor. Finally, CFD with different parameters was conducted to verify the feasibility of the optimization scheme. The numerical results give the recommended range of parameters under different control schemes. In addition, the relationship between throttle pressure drop and pressure wave waveform is found through comparison with previous research of the team, which provides a new research idea for the optimization of the pressure wave in the future.

Microvascular Doppler-assisted Microsurgical Left Spermatic-inferior Epigastric Vein Anastomosis for Treating Nutcracker Syndrome-associated Varicocele.

Background: Nutcracker syndrome (NCS) is a rare cause of varicocele and its treatment is still controversial. Objective: To summarize the surgical strategy and outcomes of microvascular Doppler (MVD)-assisted microsurgical left spermatic-inferior epigastric vein anastomosis (MLSIEVA) with microsurgical varicocelectomy (MV) at the same incision for treating NCS-associated varicocele. Design setting and participants: A retrospective analysis of 13 cases of NCS-associated varicocele between July 2018 and January 2022 was performed. Surgical procedure: A small incision in the body projection corresponding to the deep inguinal ring was chosen as the surgical incision. All patients underwent MLSIEVA and MV with the assistance of MVD. Measurements: Patients received real-time Doppler ultrasound (DUS) before and after surgery; urine red blood cells and protein were tested, with a follow-up time of 12-53 mo. Results and limitations: All patients had no intraoperative complications, and all postoperative symptoms of hematuria or proteinuria, scrotal swelling, and low back pain disappeared. Comparing pre- and postoperative DUS, two patients did not show any improvement in their postoperative measurements. However, in the remaining patients, the internal diameter of the renal vein at the hilum portion and at the aortomesenteric angle portion, as well as their ratio, improved significantly compared with preoperative measurements. No complications or recurrence of varicocele was observed during postoperative follow-up. Conclusions: Our study suggests that MVD-assisted MLSIEVA with MV is feasible with no major short-term complication and effective regarding the treatment of varicocele and NCS. Patient summary: We investigated microsurgery mediated by microultrasound for the treatment of varicocele associated with nutcracker syndrome. We found this procedure to be safe and effective with good long-term results.

Semi-Supervised CT Lesion Segmentation Using Uncertainty-Based Data Pairing and SwapMix.

Semi-supervised learning (SSL) methods show their powerful performance to deal with the issue of data shortage in the field of medical image segmentation. However, existing SSL methods still suffer from the problem of unreliable predictions on unannotated data due to the lack of manual annotations for them. In this paper, we propose an unreliability-diluted consistency training (UDiCT) mechanism to dilute the unreliability in SSL by assembling reliable annotated data into unreliable unannotated data. Specifically, we first propose an uncertainty-based data pairing module to pair annotated data with unannotated data based on a complementary uncertainty pairing rule, which avoids two hard samples being paired off. Secondly, we develop SwapMix, a mixed sample data augmentation method, to integrate annotated data into unannotated data for training our model in a low-unreliability manner. Finally, UDiCT is trained by minimizing a supervised loss and an unreliability-diluted consistency loss, which makes our model robust to diverse backgrounds. Extensive experiments on three chest CT datasets show the effectiveness of our method for semi-supervised CT lesion segmentation.

[Effect of MiR-424-5p on the Drug Resistance of Diffuse Large B-Cell Lymphoma Cells by Regulating PD-1/PD-L1 Signaling Pathway].

OBJECTIVE: To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway. METHODS: Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP. RESULTS: Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001). CONCLUSION: Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.

Altered microbiota profile in seminal vesicles of men presenting with refractory hematospermia.

BACKGROUND: Currently, no recognized evidence is known about the bacterial communities found within seminal vesicles (SV) of men presenting with refractory hematospermia. METHODS AND RESULTS: Fifteen male patients with refractory hematospermia or anejaculation were enrolled, and 15 SV-Infection (SV-In) samples from SV with hemorrhage and/or stones, 11 SV-Control (SV-C) samples from SV with non-infection, and 14 Urine (Urine) samples from posterior urethra were obtained via transurethral seminal vesiculoscopy. Then the high-throughput 16 S rRNA gene sequencing method was performed to characterize the microbiota profile. Finally, a total of 1535 operational taxonomic units (OTUs) were found, 1295 OTUs were shared across three groups, 7 OTUs, 45 OTUs, and 48 OTUs were unique to SV-C group, SV-In group, and Urine group, respectively. The 5 top bacterial phyla (mean relative abundance) in all samples were Firmicutes (52.08%), Bacteroidetes (21.69%), Proteobacteria (12.72%), Actinobacteria (9.64%), and Fusobacteria (1.62%), the 5 top bacterial genera in all samples were Bacteroides (9.13%), Lactobacillus (5.38%), Bifidobacterium (5.35%), Faecalibacterium (5.10%), and Allobaculum (3.34%), of which Bifidobacterium had the highest level in SV-C samples and had a significant difference (P < 0.05) across all groups. Differential analysis showed genera Leuconostoc and LachnospiraceaeFCS020group were identified as biomarkers in the SV-In microbiota. CONCLUSION: Altered microbiota composition in seminal vesicles is related to refractory hematospermia in men, and the distribution of genus Leuconostoc or LachnospiraceaeFCS020group within seminal vesicles may interact with hematospermia. This study provides clues for the diagnosis and treatment of this urologic disorder.

Patterns of social participation and impacts on memory among the older people.

This study employs latent class analysis to analyze the social participation patterns of elderly Chinese, as well as the impact of different social participation patterns on memory. According to the results, older persons exhibit four distinct social participation patterns. and senior citizens with a strong emphasis on entertainment had a better memory than those with a low participation level. Although there was no difference in urban elders' memory across the four social engagement patterns, the connection varied significantly between urban and rural seniors. As a result, it is suggested that the elderly's memory be improved by protecting their right to social involvement, enriching the style and content of social participation, and assuring the continuity of their social obligations.

Case report: Two cases of primary paratesticular liposarcoma.

Paratesticular liposarcoma is a sporadic urological tumor. We report the clinical presentation, treatment course, and prognosis of 2 cases of primary paratesticular liposarcoma with different pathological types, with the aim of further understanding the diagnosis and treatment of this rare disease. Case 1 was a 53-years-old male patient who presented with left scrotal enlargement with swelling 3 years ago and was considered to have a testicular malignancy on preoperative CT scan and enhanced MRI. The patient underwent resection of the left scrotal mass and left orchiectomy under general anaesthesia. Histopathological study confirmed the diagnosis of dedifferentiated liposarcoma. At the 4-months follow-up, no local recurrence or distant metastasis was observed. Case 2 is a 42-years-old male patient with a left scrotal mass which was discovered six months ago. Preoperatively, he underwent CT plain and enhanced MRI examinations suggesting an intra-scrotal occupancy. The patient underwent scrotoscopic excision of the left scrotal mass under general anesthesia. Histopathological studies confirmed the diagnosis of highly differentiated liposarcoma. At the 10-months follow-up, no local recurrence or distant metastasis was observed. Preoperative differential diagnosis of paratesticular liposarcoma should be noted with testicular tumor and extra-abdominal hernia. Extensive local excision and, if necessary, concomitant radical testicular resection is the treatment of choice. If the tumor in the scrotum spreads to the inguinal region, surgical removal with the aid of a scrotoscope may be attempted. This procedure avoids the formation of a large incision in the inguinal region compared to traditional open surgery. Patients commonly experience local recurrence and less distant metastases after surgery, so long-term follow-up is recommended.

The value of NSE to predict ICU mortality in patients with septic shock: A prospective observational study.

To investigate the predictive value of neuron-specific enolase (NSE) on intensive care unit (ICU) mortality in patients with septic shock. Seventy-five patients with septic shock hospitalized in the emergency intensive care unit (EICU) of Hebei General Hospital from March 2020 to September 2021 were included, and the patients' baseline characteristics and laboratory findings were collected. NSE levels on the first and fourth days after admission were retrieved. NSE% [(NSEday1 - NSEday4)/NSEday1 × 100%] and δNSE (NSEday1 - NSEday4) were calculated. The outcome indicator was ICU mortality. The patients were divided into the survivors group (n = 57) and the nonsurvivors group (n = 18). Multivariate analysis was performed to assess the relationship between NSE and ICU mortality. The predictive value of NSE was evaluated using receiver operating characteristic (ROC) curve. There were no significant differences in age, gender, systolic blood pressure (SBP), heart rate (HR), acute physiology and chronic health evaluation II score (APACHE II score), source of infection, and comorbidities between the 2 groups (all P > .05). Interleukin-6 (IL-6), NSE (day1), and NSE (day4) were significantly higher in patients in the nonsurvivors group (all P < .05), and there were no statistical differences in other laboratory tests between the 2 groups (all P > .05). APACHE II score, IL-6, lactate (Lac), total bilirubin (TBil), NSE (day1), and NSE (day4) showed a weak positive correlation with ICU mortality in patients with septic shock (all P < .05). Multivariate logistic regression analysis demonstrated that APACHE II score (odds ratio [OR] = 1.166, 95% confidence interval [95% confidence interval [CI]] 1.005-1.352, P = .042), IL-6 (OR = 1.001, 95% CI 1.000-1.001, P = .003) and NSE (day4) (OR = 1.099, 95% CI 1.027-1.176, P = .006) were independently associated with the ICU mortality of sepsis shock patients. The area under the curve (AUCs) of APACHE II score, IL-6, NSE (day1), and NSE (day4) for predicting prognosis were 0.650, 0.694, 0.758 and 0.770, respectively (all P < .05). NSE(day4) displayed good sensitivity and specificity (Sn = 61.11%, Sp = 91.23%) for predicting ICU mortality with a cutoff value of 25.94 ug/L. High-level NSE (day4) is an independent predictor of ICU mortality in sepsis shock patients, which may become a good alternate option for evaluating sepsis severity. More extensive studies are needed in the future to demonstrate the prognosis value of NSE.

Elastography and contrast-enhanced ultrasound to assess the effect of varicocelectomy: A case-controlled study.

To evaluate the changes in testicular stiffness and microcirculation caused by spermatic vein ligation in patients with varicocele, we conducted a case-controlled study. A total of 27 grade III left varicocele cases were enrolled. Testicular stiffness and perfusion were evaluated by shear wave elastography and contrast-enhanced ultrasound during subinguinal microscopic varicocelectomy. The external and the internal parenchyma of bilateral testes were selected to compare the shear wave velocity of bilateral testes during the spermatic vein ligation. We mapped and compared the intensity-time curves following bolus contrast injection three times in the same region of interest. Initially, the shear wave velocity of the left internal parenchyma was higher than the right side (1.10 ± 0.06 m/s vs. 1.00 ± 0.03 m/s). It decreased (1.09 ± 0.06 m/s) (p < 0.05) after ligation. Meanwhile, the left epididymis had the higher agent peak intensity (0.90 × 10E-5 AU), the largest area under the curve (80.20 × 10E-5 AU s), and the longest washout area (54.35 × 10E-5 AU s). In addition, the left internal parenchyma presented a sharper slope (0.18 × 10E-5 AU/s) (p < 0.05). In conclusion, the spermatic vein ligation improved the perfusion of the internal testicular parenchyma, but it could temporally deteriorate the stasis of the epididymis. These changes caused softer testicular parenchyma.

NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial-mesenchymal transition.

BACKGROUND: Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis. RESULTS: We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial-mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-ß1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM. CONCLUSIONS: Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.

Urban-Rural Differences: The Impact of Social Support on the Use of Multiple Healthcare Services for Older People.

Background: There are many kinds of chronic diseases, high incidence and high hospitalization rate in older people caused by population aging. The increasing demand for healthcare services has become an increasingly prominent problem in Chinese society. The purpose of this paper is to explore the influence of social support on multiple healthcare services for older people and the urban-rural differences among them. Methods: The data are from our field survey in Shaanxi province in 2019. Using the Anderson model as the basic explanatory framework, this paper uses the Tobit-model to analyses the impact of social support for older people on the utilization of therapeutic healthcare services, and the Logit-model to analyze the impact of living arrangements and social support on the utilization of preventive healthcare services for older people. Results: This paper examines the impact of formal and informal support on outpatient, inpatient, and preventive healthcare services for older people, provides an in-depth analysis of the differences in the impact of social support on healthcare service utilization between urban and rural older people and analyses the contribution of various factors to the impact. The coefficient effect is divided into two parts: the coefficient "premium" of urban older people relative to urban and rural older people as a whole, which accounts for 10.8% of the total difference; and the "premium" of urban and rural older people as a whole to rural older people, which accounts for 18.9% of the total difference. The coefficient effect accounts for 29.7 per cent of the total difference. Conclusions: Rural older people place greater importance on the quantity of formal social support, while urban older people place greater importance on the quality of formal social support. The phenomenon of raising children for old age was evident in the use of healthcare services by rural older people, while the phenomenon of distant relatives being better than close neighbors was evident in the use of healthcare services by urban older people. Free preventive healthcare services in rural China have largely compensated for the lack of health benefits for rural older people.

Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota.

Liver metastasis is the major cause of death in colorectal cancer (CRC) patients. Nevertheless, the underlying mechanisms remain unknown. Gut microbiota intricately affect the initiation and progression of CRC by instigating immune response through the secretion of pro-inflammatory cytokines. In this study, we investigated the contribution of Fusobacterium nucleatum (F.nucleatum) to the microbiota-liver axis of CRC in mice, focusing on the correlation between liver immunity and gut microbiota alterations. When F. nucleatum was orally administered to mice, CRC liver metastasis was evidently exaggerated and accompanied by noticeable deleterious effects on body weight, cecum weight, and overall survival time. Further evaluation of the immune response and cytokine profiles revealed a substantial increase in the levels of pro-inflammatory cytokines such as IL6, IL12, IL9, IL17A, CXCL1, MCP-1, TNF-α, and IFN-γ in the plasma of mice treated with F. nucleatum as compared to that in the untreated control mice. Besides, hepatic immune response was also modulated by recruitment of myeloid-derived suppressor cells, reduction in the infiltration of natural killer (NK) and T helper-17 (Th17) cells, as well as increase in regulatory T cell accumulation in the liver. Additionally, sustained F. nucleatum exposure abridged the murine gut microbiota diversity, inducing an imbalanced and restructured intestinal microflora. In particular, the abundance of CRC-promoting bacteria such as Enterococcus and Escherichia/Shigella was evidently elevated post F. nucleatum treatment. Thus, our findings suggest that F. nucleatum might be an important factor involved in promoting CRC liver metastasis by triggering of liver immunity through the regulation of gut microbiota structure and composition.

Kinsenoside Protects Against Radiation-Induced Liver Fibrosis via Downregulating Connective Tissue Growth Factor Through TGF-ß1 Signaling.

Radiation-induced liver fibrosis (RILF) is a serious complication of the radiotherapy of liver cancer, which lacks effective prevention and treatment measures. Kinsenoside (KD) is a monomeric glycoside isolated from Anoectochilus roxburghii, which has been reported to show protective effect on the early progression of liver fibrosis. However, the role of KD in affecting RILF remains unknown. Here, we found that KD alleviated RILF via downregulating connective tissue growth factor (CTGF) through TGF-ß1 signaling. Sprague-Dawley rats were administered with 20 mg/kg KD per day for 8 weeks after a single 30Gy irradiation on the right part of liver, and tumor-bearing nude mice were administered with 30 mg/kg KD per day after a single fraction of 10Gy on the tumor inoculation site. Twenty-four weeks postirradiation, we found that the administration of KD after irradiation resulted in decreased expression of α-SMA and fibronectin in the liver tissue while had no adverse effect on the tumor radiotherapy. Besides, KD inhibited the activation of hepatic stellate cells (HSCs) postirradiation via targeting CTGF as indicated by the transcriptome sequencing. Results of the pathway enrichment and immunohistochemistry suggested that KD reduced the expression of TGF-ß1 protein after radiotherapy, and exogenous TGF-ß1 induced HSCs to produce α-SMA and other fibrosis-related proteins. The content of activated TGF-ß1 in the supernatant decreased after treatment with KD. In addition, KD inhibited the expression of the fibrosis-related proteins by regulating the TGF-ß1/Smad/CTGF pathway, resulting in the intervention of liver fibrosis. In conclusion, this study revealed that KD alleviated RILF through the regulation of TGFß1/Smad/CTGF pathway with no side effects on the tumor therapy. KD, in combination with blocking the TGF-ß1 pathway and CTGF molecule or not, may become the innovative and effective treatment for RILF.

miR-199b-3p contributes to acquired resistance to cetuximab in colorectal cancer by targeting CRIM1 via Wnt/ß-catenin signaling.

BACKGROUND: Despite advances in the development of efficient chemotherapy, the treatment of colorectal cancer (CRC) remains a challenge due to acquired chemoresistance. It has been reported that microRNAs (miRNAs) dysregulation is associated with the development of chemoresistance. Recently, the expression of miR-199b-3p has been found to be significantly different between cetuximab (CTx)-resistant and -sensitive CRC cells. However, its role and the underlying mechanisms in acquired chemoresistance to CTx in CRC are still obscure. METHODS: Here we report that miR-199b-3p is significantly up-regulated in both CTx-resistant (CTxR) CRC tissues and cell lines. RESULTS: Functional assays showed that suppressing miR-199b-3p could improve the sensitivity of CRC-CTxR cells to CTx, thereby reducing cell proliferation, migration and invasion, and enhancing cell apoptosis. Mechanistic studies revealed that CRIM1 is a direct target of miR-199b-3p in CRC-CTxR cells; and the effect of miR-199b-3p on CTx-resistance was exerted by regulating the Wnt/ß-catenin signaling pathway via CRIM1. Furthermore, mice xenograft models were established and confirmed that down-regulating miR-199b-3p restores the inhibition effect of CTx on tumor growth in CRC-CTxR. Collectively, our data suggest that silencing miR-199b-3p could enhance the anti-tumor effects of CTx on CTx-resistant CRC in vitro and in vivo by activating Wnt/ß-catenin signaling via the down-regulation of CRIM1. CONCLUSIONS: Our findings suggest miR-199b-3p might serve as a promising therapeutic target against CTx resistant CRC, and provide scientific information for exploring novel strategies of improving the efficacy of CTx for CRC patients.