Computed tomography and structured light imaging guided orthopedic navigation puncture system: effective reduction of intraoperative image drift and mismatch.

Background: Image-guided surgical navigation systems are widely regarded as the benchmark for computer-assisted surgical robotic platforms, yet a persistent challenge remains in addressing intraoperative image drift and mismatch. It can significantly impact the accuracy and precision of surgical procedures. Therefore, further research and development are necessary to mitigate this issue and enhance the overall performance of these advanced surgical platforms. Objective: The primary objective is to improve the precision of image guided puncture navigation systems by developing a computed tomography (CT) and structured light imaging (SLI) based navigation system. Furthermore, we also aim to quantifying and visualize intraoperative image drift and mismatch in real time and provide feedback to surgeons, ensuring that surgical procedures are executed with accuracy and reliability. Methods: A CT-SLI guided orthopedic navigation puncture system was developed. Polymer bandages are employed to pressurize, plasticize, immobilize and toughen the surface of a specimen for surgical operations. Preoperative CT images of the specimen are acquired, a 3D navigation map is reconstructed and a puncture path planned accordingly. During surgery, an SLI module captures and reconstructs the 3D surfaces of both the specimen and a guiding tube for the puncture needle. The SLI reconstructed 3D surface of the specimen is matched to the CT navigation map via two-step point cloud registrations, while the SLI reconstructed 3D surface of the guiding tube is fitted by a cylindrical model, which is in turn aligned with the planned puncture path. The proposed system has been tested and evaluated using 20 formalin-soaked lower limb cadaver specimens preserved at a local hospital. Results: The proposed method achieved image registration RMS errors of 0.576 ± 0.146 mm and 0.407 ± 0.234 mm between preoperative CT and intraoperative SLI surface models and between preoperative and postoperative CT surface models. In addition, preoperative and postoperative specimen surface and skeletal drifts were 0.033 ± 0.272 mm and 0.235 ± 0.197 mm respectively. Conclusion: The results indicate that the proposed method is effective in reducing intraoperative image drift and mismatch. The system also visualizes intraoperative image drift and mismatch, and provides real time visual feedback to surgeons.

Squamous cell carcinoma arising from mature cystic teratoma of the ovary: A case report.

Mature cystic teratoma of the ovary (MCTO) is a type of common disease in clinic. However, the malignant transformation of MCTO occurred rarely, with many unexplained questions. To the best of our knowledge, owing to the rarity of squamous cell carcinoma (SCC) in MCTO, even though there are some previous research works concerning about this rare disease, further exploration and discussion is still necessary to reveal unknown aspects. We present a case of pathologically confirmed SCC in MCTO in a 54-year-old female patient, who underwent surgery and subsequent adjuvant chemotherapy. After the treatment, she recovered well and was followed up until now. SCC in MCTO occurred rarely; clinicians should abandon habitual concepts and make targeted management individually.

Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. AIM OF THE STUDY: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. MATERIALS AND METHODS: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. RESULTS: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. CONCLUSIONS: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.

Laparoscopic Sigmoid Vaginoplasty for the Treatment of Mayer-Rokitansky-Kuster-Hauser Syndrome in a Single Center: 20 years' Experience.

INTRODUCTION AND HYPOTHESIS: We investigate the feasibility, safety, and clinical therapeutic effect of laparoscopic sigmoid vaginoplasty in women with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. METHODS: We performed a retrospective case review cohort study of 56 patients with MRKHs undergoing laparoscopic sigmoid vaginoplasty in Wuhan Union Hospital between 2000 and 2020, and all patients were followed up. RESULTS: The median operating time was 165 min (120-420 min). The median hospital stay was 10 days (rang 7-15 days). A functional neovagina was created 11-15 cm in length and two fingers in breadth in all patients. No introitus stenosis was observed. No intra- or post-operative complications occurred. Two patients were lost to follow-up after 3 months of outpatient visits. Six patients had no intercourse and were required to wear a vaginal mold occasionally. None of the patients had complained of local irritation or dyspareunia. Patients who had post-surgery sexual intercourse were satisfied with their sexual life and the mean total Female Sexual Function Index (FSFI) score was 25.17 ± 0.63. The cosmetic results were excellent. CONCLUSIONS: The laparoscopic sigmoid vaginoplasty can achieve the goal of making a functional neovagina. The main advantage of this surgical technique is that it is minimally invasive and that there are fewer complications post-operation. It is an acceptable procedure for patients with MRKH syndrome.

Application of 18ß-glycyrrhetinic acid in the structural modification of natural products: a review.

18ß-Glycyrrhetinic acid (GA) is an oleane-type pentacyclic triterpene saponin obtained from glycyrrhizic acid by removing 2 glucuronic acid groups. GA and its analogues are active substances of glycyrrhiza aicd, with similar structure and important pharmacological effects such as anti-inflammatory, anti-diabetes, anti-tumor and anti-fibrosis. Although GA combined compounds are in the clinical trial stages, its application potential is severely restricted by its low bioavailability, water solubility and membrane permeability. In this article, synthetic methods and structure-activity relationships (SARs) of GA derivatives from 2018 to present are reviewed based on pharmacological activity. It is hoped that this review can provide reference for the future development of potential GA preclinical candidate compounds, and furnish ideas for the development of pentacyclic triterpenoid lead compounds.

Towards humanlike grasp in robotic hands: mechanical implementation of force synergies.

In the field of robotic hands, finger force coordination is usually achieved by complex mechanical structures and control systems. This study presents the design of a novel transmission system inspired from the physiological concept of force synergies, aiming to simplify the control of multifingered robotic hands. To this end, we collected human finger force data during six isometric grasping tasks, and force synergies (i.e. the synergy weightings and the corresponding activation coefficients) were extracted from the concatenated force data to explore their potential for force modulation. We then implemented two force synergies with a cable-driven transmission mechanism consisting of two spring-loaded sliders and five V-shaped bars. Specifically, we used fixed synergy weightings to determine the stiffness of the compression springs, and the displacements of sliders were determined by time-varying activation coefficients. The derived transmission system was then used to drive a five-finger robotic hand named SYN hand. We also designed a motion encoder to selectively activate desired fingers, making it possible for two motors to empower a variety of hand postures. Experiments on the prototype demonstrate successful grasp of a wide range of objects in everyday life, and the finger force distribution of SYN hand can approximate that of human hand during six typical tasks. To our best knowledge, this study shows the first attempt to mechanically implement force synergies for finger force modulation in a robotic hand. In comparison to state-of-the-art robotic hands with similar functionality, the proposed hand can distribute humanlike force ratios on the fingers by simple position control, rather than resorting to additional force sensors or complex control strategies. The outcome of this study may provide alternatives for the design of novel anthropomorphic robotic hands, and thus show application prospects in the field of hand prostheses and exoskeletons.

Computed tomography Osteoabsorptiometry: Review of bone density, mechanical strength of material and clinical application.

Computed Tomography (CT) imaging is an effective non-invasive examination. It is widely used in the diagnosis of fractures, arthritis, tumor, and some anatomical characteristics of patients. The density value (Hounsfield unit, HU) of a material in computed tomography can be the same for materials with varying elemental compositions. This value depends on the mass density of the material and the degree of X-ray attenuation. Computed Tomography Osteoabsorptiometry (CTOAM) imaging technology is developed on the basis of CT imaging technology. By applying pseudo-color image processing to the articular surface, it is used to analyze the distribution of bone mineralization under the articular cartilage, evaluate the position of prosthesis implantation, track the progression of osteoarthritis, and determine the joint injury prognosis. Furthermore, this technique was combined with indentation testing to discuss the relationship between the high bone density area of the articular surface, the mechanical strength of the bone, and the anchorage stability of the implant, in addition to the study of the relationship between mechanical strength and bone density. This narrative study discusses the pre- and postoperative evaluation of medical device implantation position, orthopedic surgery, and the clinical treatment of bone injury and degeneration. It also discusses the research status of CTOAM technology in image post-processing engineering and the relationship between bone material and mechanical strength.

A Clinical Study on the Treatment of Recurrent Chiari (Type I) Malformation with Syringomyelia Based on the Dynamics of Cerebrospinal Fluid.

Objective: Combining the dynamics of cerebrospinal fluid, our study investigates the clinical effects of syringomyelia after the combination of fourth ventricle-subarachnoid shunt (FVSS) for recurrent Chiari (type I) malformations after cranial fossa decompression (foramen magnum decompression (FMD)). Methods: From December 2018 to December 2020, 15 patients with recurrent syringomyelia following posterior fossa decompression had FVSS surgery. Before and after the procedure, the clinical and imaging data of these individuals were retrospectively examined. Results: Following FVSS, none of the 15 patients experienced infection, nerve injury, shunt loss, or obstruction. 13 patients improved dramatically after surgery, while 2 patients improved significantly in the early postoperative period, but the primary symptoms returned 2 months later. The Japanese Orthopedic Association (JOA) score was 12.67 ± 3.95, which was considerably better than preoperatively (t = 3.69, P0.001). The MRI results revealed that the cavities in 13 patients were reduced by at least 50% compared to the cavities measured preoperatively. The shrinkage rate of syringomyelia was 86.67% (13/15). One patient's cavities nearly vanished following syringomyelia. The size of the cavity in the patient remain unchanged, and the cavity's maximal diameter was significantly smaller than the size measured preoperatively (P < 0.001) PC-MRI results indicated that the peak flow rate of cerebrospinal fluid at the central segment of the midbrain aqueduct and the foramen magnum in patients during systole and diastole were significantly reduced after surgery (P < 0.05). Conclusion: After posterior fossa decompression, FVSS can effectively restore the smooth circulation of cerebrospinal fluid and alleviate clinical symptoms in patients with recurrent Chiari (type I) malformation and syringomyelia. It is a highly effective way of treatment.

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-κB signaling pathway.

BACKGROUND: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. METHODS: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. RESULTS: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). CONCLUSION: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

Resveratrol modulates Toxoplasma gondii infection induced liver injury by intervening in the HMGB1/TLR4/NF-κB signaling pathway.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can cause liver diseases in the host, including hepatitis and hepatomegaly. High mobility group box 1 (HMGB1) is the main inflammatory mediator causing cell injury or necrosis. HMGB1 binds to toll like receptor 4 (TLR4), then activates the nuclear factor-κB (NF-κB) signaling pathway, which promotes the release of inflammatory factors. Our previous studies showed that HMGB1 mediated TLR4/NF-κB signaling pathway plays an important role in liver injury induced by T. gondii infection. Resveratrol (RSV) is a small polyphenol, which has anti-inflammatory, anti-cancer, anti-T. gondii effect. However, the effect of RSV on liver injury caused by T. gondii infection is unclear. This study used the RH strain tachyzoites of T. gondii to infect murine liver line, NCTC-1469 cells to establish an in vitro model and acute infection of mice for the in vivo model to explore the protective effect of RSV on liver injury induced by T. gondii infection. The results showed that RSV inhibited the proliferation of T. gondii in the liver, reduced the alanine aminotransferase/aspartate aminotransferase levels and pathological liver damage. Additionally, RSV inhibited the production of tumor necrosis factor-α, inducible nitric oxide synthase and HMGB1 by interfering with the TLR4/NF-κB signaling pathway. These results indicate that RSV can protect liver injury caused by T. gondii infection by intervening in the HMGB1/TLR4/NF-κB signaling pathway. This study will provide a theoretical basis for RSV treatment of T. gondii infection induced liver injury.

Efficacy of Antiviral Treatment in Liver Biopsy-Proven Immune-Tolerant Chronic Hepatitis B Patients: A Retrospective Cohort Study.

The optimal timing of initiating antiviral treatment for immune-tolerant (IT) patients remains unknown. We conducted this study in liver biopsy-proven IT patients to compare the long-term outcomes of untreated and treated patients suffering non-cirrhotic chronic hepatitis B (CHB). This retrospective cohort study recruited 171 consecutive treatment-naïve CHB patients who completed liver biopsy test. Patients were stratified into IT (n = 60), mildly-active (MA; n = 31), immune-active (IA; n = 80), according to alanine aminotransferase (ALT) and liver biopsy data. One hundred and nine patients receiving antiviral treatment constituted the treated set, and 62 patients under close follow-up comprised the untreated set. Primary outcomes were virological response, HBeAg seroconversion, HBsAg loss, ALT normalization, and liver stiffness measurement normalization (NCT03740789). The study population was predominantly male (62.6%) with a mean age of 31 years. The proportion of virological response in treated patients in the MA phase was 57.1%, and the proportion of HBeAg seroconversion was 28.6%, which showed no difference with the 43.8% virological response and 31.5% HBeAg seroconversion in IA patients. The proportions of virological response and seroconversion were 18.2 and 9.1%, respectively, in the IT phase, which were lower than the rates in the MA and IA phases. However, 95.5% of IT patients persisted normal ALT, and 100% of IT patients persisted normal liver stiffness measurement in the treated group. Therefore, antiviral treatment should be considered for CHB patients with high viral load regardless of phase to minimize further damage to hepatocytes.

Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza glabra L., a traditional medicinal, has a history of thousands of years. It is widely used in clinic and has been listed in Chinese Pharmacopoeia. Licochalcone A is a phenolic chalcone compound and a characteristic chalcone of Glycyrrhiza glabra L. It has many pharmacological activities, such as anti-cancer, anti-inflammatory, anti-viral and anti-angiogenic activities. AIM OF THE STUDY: In this study, we explored the anti-tumor activity and potential mechanism of licochalcone A in vitro and in vivo. MATERIALS AND METHODS: In vitro, the mechanism of licochalcone A at inhibiting PD-L1 expression was investigated by molecular docking, western blotting, RT-PCR, flow cytometry, immunofluorescence and immunoprecipitation assays. The co-culture model of T cells and tumor cells was used to detect the activity of cytotoxic T lymphocytes. Colony formation, EdU labelling and apoptosis assays were used to detect changes in cellular proliferation and apoptosis. In vivo, anti-tumor activity of licochalcone A was assessed in a xenograft model of HCT116 cells. RESULTS: In the present study, we found that licochalcone A suppressed the expression of programmed cell death ligand-1 (PD-L1), which plays a key role in regulating the immune response. In addition, licochalcone A inhibited the expressions of p65 and Ras. Immunoprecipitation experiment showed that licochalcone A suppressed the expression of PD-L1 by blocking the interaction between p65 and Ras. In the co-culture model of T cells and tumor cells, licochalcone A pretreatment enhanced the activity of cytotoxic T lymphocytes and restored the ability to kill tumor cells. In addition, we showed that licochalcone A inhibited cell proliferation and promoted cell apoptosis by targeting PD-L1. In vivo xenograft assay confirmed that licochalcone A inhibited the growth of tumor xenografts. CONCLUSION: In general, these results reveal the previously unknown properties of licochalcone A and provide new insights into the anticancer mechanism of this compound.

Ginsenoside Rh2 attenuates microglial activation against toxoplasmic encephalitis via TLR4/NF-κB signaling pathway.

BACKGROUND: Ginsenoside Rh2 (GRh2) is a characterized component in red ginseng widely used in Korea and China. GRh2 exhibits a wide range of pharmacological activities, such as anti-inflammatory, antioxidant, and anticancer properties. However, its effects on Toxoplasma gondii (T. gondii) infection have not been clarified yet. METHODS: The effect of GRh2 against T. gondii was assessed under in vitro and in vivo experiments. The BV2 cells were infected with tachyzoites of T. gondii RH strain, and the effects of GRh2 were evaluated by MTT assay, morphological observations, immunofluorescence staining, a trypan blue exclusion assay, reverse transcription PCR, and Western blot analyses. The in vivo experiment was conducted with BALB/c mice inoculated with lethal amounts of tachyzoites with or without GRh2 treatment. RESULTS AND CONCLUSION: The GRh2 treatment significantly inhibited the proliferation of T. gondii under in vitro and in vivo studies. Furthermore, GRh2 blocked the activation of microglia and specifically decreased the release of inflammatory mediators in response to T. gondii infection through TLR4/NF-κB signaling pathway. In mice, GRh2 conferred modest protection from a lethal dose of T. gondii. After the treatment, the proliferation of tachyzoites in the peritoneal cavity of infected mice markedly decreased. Moreover, GRh2 also significantly decreased the T. gondii burden in mouse brain tissues. These findings indicate that GRh2 exhibits an anti-T. gondii effect and inhibits the microglial activation through TLR4/NF-κB signaling pathway, providing the basic pharmacological basis for the development of new drugs to treat toxoplasmic encephalitis.

Antidepressive Effect of Arctiin by Attenuating Neuroinflammation via HMGB1/TLR4- and TNF-α/TNFR1-Mediated NF-κB Activation.

Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-like effects. However, the antidepressant-like effects of arctiin, its precursor, remain unknown. In this study, we investigated the antidepressant-like effects of arctiin and its underlying mechanisms by in vivo and in vitro experiments in mice. Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests. Arctiin decreased neuronal damage in the prefrontal cortex (PFC) of the brain. Arctiin also attenuated the levels of three inflammatory mediators, indoleamine 2,3-dioxygenase, 5-hydroxytryptamine, and dopamine, that were elevated in the PFC or serum of chronic unpredictable mild stress (CUMS)-exposed mice. Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)- and tumor necrosis factor-α (TNF-α)/TNF receptor 1 (TNFR1)-mediated nuclear factor-kappa B (NF-κB) activation in the PFC of CUMS-exposed mice and HMGB1- or TNF-α-stimulated primary cultured microglia. These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammation via the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways.

Associations of polymorphisms in interleukins with susceptibility to breast cancer: Evidence from a meta-analysis.

BACKGROUND: Associations between polymorphisms in interleukins and breast cancer (BC) were already investigated by many studies, yet with controversial findings. The aim of this meta-analysis was to better clarify associations between polymorphisms in interleukins and BC by combing the results of all relevant articles. METHODS: Eligible articles were searched from Pubmed, Embase, Web of Science and CNKI. We used Review Manager to combine the results of eligible studies. RESULTS: Fifty-seven studies were included in this meta-analysis. We found that IL-6 rs1800796 (dominant comparison: OR = 0.70, 95% CI 0.53-0.92), IL-8 rs4073 (dominant comparison: OR = 0.74, 95% CI 0.61-0.89; over-dominant comparison: OR = 1.16, 95% CI 1.05-1.29; allele comparison: OR = 0.82, 95% CI 0.69-0.89), IL-10 rs1800896 (recessive comparison: OR = 1.28, 95% CI 1.12-1.47) and IL-18 rs1946518 (dominant comparison: OR = 0.80, 95% CI 0.65-0.97; allele comparison: OR = 0.74, 95% CI 0.59-0.93) polymorphisms were all significantly associated with BC in overall combined analyses. In subgroup analyses, we noticed that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800896, IL-18 rs1946518 and rs187238 polymorphisms were all significantly associated with susceptibility to BC in East Asians from China. CONCLUSIONS: Collectively, this meta-analysis demonstrated that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800896, IL-18 rs1946518 and rs187238 polymorphisms may confer susceptibility to BC for East Asians from China.

Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer.

BACKGROUND: Aberrant activation of STAT3 is frequently encountered and promotes survival, cellular proliferation, migration, invasion and angiogenesis in tumor cell. Convallatoxin, triterpenoid ingredient, exhibits anticancer pharmacological properties. PURPOSE: In this work, we investigated the anticancer potential of convallatoxin and explored whether convallatoxin mediates its effect through interference with the STAT3 activation in colorectal cancer cells. METHODS: In vitro, the underlying mechanisms of convallatoxin at inhibiting STAT3 activation were investigated by homology modeling and molecular docking, luciferase reporter assay, MTT assay, RT-PCR, Western blotting and immunofluorescence assays. Changes in cellular proliferation, apoptosis, migration, invasion and angiogenesis were analyzed by EdU labeling assay, colony formation assay, flow cytometry assay, wound-healing assay, matrigel transwell invasion assay and tube formation assays. And in vivo, antitumor activity of convallatoxin was assessed in a murine xenograft model of HCT116 cells. RESULTS: Convallatoxin decreased the viability of colorectal cancer lines. Moreover, convallatoxin reduced the P-STAT3 (T705) via the JAK1, JAK2, and Src pathways and inhibited serine-727 phosphorylation of STAT3 via the PI3K-AKT-mTOR-STAT3 pathways in colorectal cancer cells. Interestingly, we discovered the crosstalk between mTOR and JAK2 in mTOR/STAT3 and JAK/STAT3 pathways, which collaboratively regulated STAT3 activation and convallatoxin play a role in it. Convallatoxin also downregulated the expression of target genes involved cell survival (e.g., Survivin, Bcl-xl, Bcl-2), proliferation (e.g., Cyclin D1), metastasis (e.g., MMP-9), and angiogenesis (e.g., VEGF). Indeed, we found that convallatoxin inhibited tube formation, migration, and invasion of endothelial cells, and inhibited the proliferation. Finally, in vivo observations were confirmed by showing antitumor activity of convallatoxin in a murine xenograft model. CONCLUSION: The result of the current study show that convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer cells and indicate that convallatoxin could be a valuable candidate for the development of colorectal cancer therapeutic.

Baseline Characteristics and Treatment Patterns of the Patients Recruited to the China Registry of Hepatitis B.

Background and Aims: Chronic hepatitis B virus (HBV) infection remains a major public health problem globally. Here, we describe the baseline characteristics and treatment profiles of HBV-infected patients recruited to the China Registry of Hepatitis B. Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data. Exclusion criteria were patients with hepatocellular carcinoma. The baseline clinical, laboratory and treatment profiles were analyzed. Results: Finally, 40,431 patients were included. The median age was 43 years, with 65.2% being men and 51.3% being positive for hepatitis B e antigen (HBeAg). The most common initial diagnosis was chronic hepatitis B (81.0%), followed by cirrhosis (9.3%), inactive carrier of hepatitis B surface antigen (HBsAg) (6.7%), and immune tolerant phase of hepatitis B infection (3.0%). Among the 21,228 patients who were on treatment, 88.0%, 10.0% and 2.0% received nucleos(t)ide analogues (NAs), interferon or combination of NAs and interferon, respectively. The proportion of patients who received preferred NAs (entecavir or tenofovir disoproxil fumarate) had increased from 13.5% in 2003 to 79.7% in 2016. Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study. About half of the patients were HBeAg-positive. NAs were the most commonly used therapy, and use of the preferred NAs had steadily increased in the past decade.

Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma.

BACKGROUND: Scavenger receptor class B type I (SR-BI) has been reported to be involved in carcinogenesis of several human cancers. However, it is currently unknown whether SR-BI plays a role in clear cell renal cell carcinoma (ccRCC). Here, we aimed to evaluate a tumor promotive mechanism for SR-BI in ccRCC. METHODS: The expression of SR-BI was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC) in ccRCC tissues and cell lines. Lipid droplets in ccRCC tissues and normal kidney tissues were examined by Oil Red O (ORO) and hematoxylin-eosin (HE) staining. The correlation between SR-BI mRNA levels and clinicopathological features was analyzed by Pearson's chi-square test or Fisher's exact test. Kaplan-Meier analysis and Cox model were used to evaluate the difference in progression-free survival (PFS) associated with expression of SR-BI. Inhibition of SR-BI was conducted by using small interfering RNA (siRNA). In vitro assays were performed to assess the impact of SR-BI knockdown on cell biological behaviors. High density lipoprotein (HDL)-cholesterol content in ccRCC cells and extracellular media was also measured after transfection with siRNA. RESULTS: The expression of SR-BI was markedly up-regulated in ccRCC tissues and tumor cell lines. ORO and HE staining revealed huge amounts of lipid droplets accumulation in ccRCC. Clinical analysis showed that over-expression of SR-BI was positively associated with tumor size, grade, distant metastasis and inversely correlated with PFS. Furthermore, SR-BI was proved to be an independent prognostic marker in ccRCC patients. The inhibition of SR-BI attenuated the tumorous behaviors of ccRCC cells, expression of metastasis and AKT pathway related proteins. The content of HDL-cholesterol was reduced in cells while increased in extracellular media after transfection with si-SR-BI. CONCLUSIONS: Our results demonstrate that SR-BI functions as an oncogene and promotes progression of ccRCC. SR-BI may serve as a potential prognostic biomarker and therapeutic target for ccRCC.

Mir-144-3p Promotes Cell Proliferation, Metastasis, Sunitinib Resistance in Clear Cell Renal Cell Carcinoma by Downregulating ARID1A.

BACKGROUND/AIMS: We previously performed microRNA (miRNA) microarray to identify effective indicators of clear cell renal cell carcinoma (ccRCC) tissue samples and preoperative/postoperative plasma in which we identified miR-144-3p as an oncomiRNA. However, the molecular mechanism of miR-144-3p remains unclear. This study aims to explore the roles of miR-144-3p in the invasion, migration and Sunitinib-resistance in ccRCC and to elucidate the underlying mechanisms. METHODS: Gain and loss of function approaches were used to investigate the cell proliferation, cycle distribution, clonogenicity, migration, invasion, chemosensitivity of miR-144-3p in vitro. The xenograft model was used to assess the effects of miR-144-3p overexpression on tumorigenesis. Bioinformatics analysis and dual-luciferase reporter assay were used to indentify AT-rich interactive domain 1A (ARID1A) as a direct target gene of miR-144-3p. Quantitative RT-PCR, Western blotting, and immunohistochemical (IHC) staining were used to explore ARID1A expression level of the mRNA and protein. RESULTS: We found that miR-144-3p overexpression enhanced cell proliferation, clonogenicity, migration, invasion, and chemoresistance in ccRCC cells. Notably, the oncotumor activities of miR-144-3p were mediated by repressing the expression of ARID1A. The downregulation of ARIDIA could promote the function of miR-144-3p in cell proliferation, metastasis and chemoresistance. Consistently, ARID1A mRNA and protein levels were decreased in ccRCC and in nude mice, and they negatively correlated with miR-144-3p. CONCLUSION: Higher miR-144-3p may enhance malignancy and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may uncover novel strategies of ccRCC treatment.