BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investig...BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.展开更多
This letter responds to Wang et al's recent publication on endoscopic biliary stenting for malignant obstructive jaundice(MOJ)by offering constructive feedback and suggestions for future research.We commend the au...This letter responds to Wang et al's recent publication on endoscopic biliary stenting for malignant obstructive jaundice(MOJ)by offering constructive feedback and suggestions for future research.We commend the authors for their comprehensive study design and execution,which included a clear delineation of study groups and a robust set of outcome measures.We suggest that future studies incorporate additional biomarkers,such as serum levels of liver enzymes and bilirubin,to provide a more nuanced understanding of liver function changes post-intervention.The study's focus on short-term survival rates is appreciated,but we recommend exploring longer-term follow-up periods to capture the full spectrum of survival outcomes.Additionally,the inclusion of quality of life assessments using validated instruments could offer a more holistic view of patient outcomes.From a critical care perspective,we advocate for the integration of advanced imaging techniques to better characterize biliary anatomy and potentially predict treatment response or complications.We believe that incor-porating these suggestions could enhance the understanding of endoscopic biliary stenting's role in MOJ management and its impact on patient outcomes,influ-encing future clinical guidelines and practice.展开更多
Microscale metallic structures enhanced by additive manufacturing technology have attracted extensive attention especially in microelectronics and electromechanical devices.Meniscus-confined electrodeposition(MCED)adv...Microscale metallic structures enhanced by additive manufacturing technology have attracted extensive attention especially in microelectronics and electromechanical devices.Meniscus-confined electrodeposition(MCED)advances microscale 3D metal printing,enabling simpler fabrication of superior metallic microstructures in air without complex equipment or post-processing.However,accurately predicting growth rates with current MCED techniques remain challenging,which is essential for precise structure fabrication and preventing nozzle clogging.In this work,we present a novel approach to electrochemical 3D printing that utilizes a self-adjusting,voxelated method for fabricating metallic microstructures.Diverging from conventional voxelated printing which focuses on monitoring voxel thickness for structure control,this technique adopts a holistic strategy.It ensures each voxel’s position is in alignment with the final structure by synchronizing the micropipette’s trajectory during deposition with the intended design,thus facilitating self-regulation of voxel position and reducing errors associated with environmental fluctuations in deposition parameters.The method’s ability to print micropillars with various tilt angles,high density,and helical arrays demonstrates its refined control over the deposition process.Transmission electron microscopy analysis reveals that the deposited structures,which are fabricated through layer-by-layer(voxel)printing,contain nanotwins that are widely known to enhance the material’s mechanical and electrical properties.Correspondingly,in situ scanning electron microscopy(SEM)microcompression tests confirm this enhancement,showing these structures exhibit a compressive yield strength exceeding 1 GPa.The indentation tests provided an average hardness of 3.71 GPa,which is the highest value reported in previous work using MCED.The resistivity measured by the four-point probe method was(1.95±0.01)×10^(−7)Ω·m,nearly 11 times that of bulk copper.These findings demonstrate the considerable advantage of this technique in fabricating complex metallic microstructures with enhanced mechanical properties,making it suitable for advanced applications in microsensors,microelectronics,and micro-electromechanical systems.展开更多
Capsule Robots(CRs)with active locomotion improve on the inefficiency of passive locomotion in capsule endoscopes,showing great potential for clinical use.However,despite the development of various CR types,efficient ...Capsule Robots(CRs)with active locomotion improve on the inefficiency of passive locomotion in capsule endoscopes,showing great potential for clinical use.However,despite the development of various CR types,efficient locomotion and functional integration remain challenges due to space limitations and increasing demands.Additionally,many CRs are overly complex,so simplifying their structure while maintaining functionality is essential.This paper presents a novel magnetically actuated CR with two internal permanent magnets for oscillating locomotion and anchoring,along with a Shape Memory Alloy(SMA)-driven actuator for biopsy sampling.Compared to existing CRs,this design simplifies the structure while ensuring biopsy functionality and leaving space for a micro-CCD.The robot’s dynamics are modeled to guide its structural design and locomotion strategy.SMA characteristics are also examined to optimize the biopsy module’s parameters,improving efficiency and success rates.The CR undergoes experiments to assess safety,locomotion performance,and functionality,with results showing stable steering,and advantages in driving height,speed,and accuracy.Finally,the CR’s biopsy capabilities are validated in a gastric model and ex vivo stomach.This work offers a novel solution for gastrointestinal disease diagnosis and treatment,enhancing the application of CRs in biomedical engineering.展开更多
BACKGROUND Knee osteoarthritis(KOA)is a chronic condition characterized by joint pain and dysfunction,driven by aging and obesity.Research indicates that the gut microbiota significantly influences KOA,potentially aff...BACKGROUND Knee osteoarthritis(KOA)is a chronic condition characterized by joint pain and dysfunction,driven by aging and obesity.Research indicates that the gut microbiota significantly influences KOA,potentially affecting inflammation and disease progression through the gut-joint axis.Traditional treatments like nonsteroidal anti-inflammatory drugs offer symptom relief but have adverse effects.Emerging therapies like electroacupuncture(EA)and Tuina(TN)have shown promise in alleviating pain and improving joint function by targeting the gut microbiota.AIM To clarify the efficacy of EA with TN in treating KOA and its effect on gut microbiota regulation.METHODS Sixty patients with KOA were allocated to EA or EA+TN(ET)group(n=30 each).Seven acupoints were punctured.The ET group received TN after each EA session.Both groups completed 12 sessions.The visual analog scale(VAS)for assessing pain and the Western Ontario and McMaster Universities osteoarthritis index(WOMAC)for measuring pain intensity,joint stiffness,and functional capacity were employed to assess clinical outcomes.Pre-and post-treatment fecal specimens underwent 16S ribosomal RNA sequencing to analyze the gut microbiota.RESULTS The ET group showed higher rates of“effective”and“markedly effective”outcomes.The VAS score of the ET group remained significantly lower than that of the EA group(P<0.001)immediately after treatment and 1 week post-treatment.The total WOMAC score(P<0.001),pain(P=0.191),stiffness(P=0.015),and function scores(P<0.001)decreased significantly in the ET group post-treatment.The gut microbiota analysis revealed no significant changes in alpha diversity in either group.Beta-diversity analysis indicated distinct patterns in the ET group before and after treatment.Significant changes in microbial abundance were detected in both groups,highlighting variations in Firmicutes,Actinobacteria,Proteobacteria,and Bacteroidetes.CONCLUSION ET outperforms EA alone in improving KOA pain,stiffness,and function,potentially via gut microbiota modulation,intestinal barrier protection,and inflammation reduction.展开更多
BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this ...BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this disease.AIM To explore the mechanism of miR-125a-5p in the pathogenesis of GC.METHODS The expression levels of miR-125a-5p,SERPINE1 and DNMT1 in GC cells and tissues were detected by real-time polymerase chain reaction(PCR)and Western blotting.Methylation-specific PCR was used to detect the level of miR-125a-5p methylation.A cell counting kit 8 assay,scratch test,and a Transwell assay were performed to detect the proliferation,migration,and invasiveness of HGC27 cells,respectively.The expression of the epithelial mesenchymal transition(EMT)-related proteins E-cadherin,N-cadherin and vimentin in HGC27 cells was detected by Western blotting,while the expression of vimentin was detected by immunofluorescence.RESULTS This study revealed that miR-125a-5p was expressed at low levels in GC clinical samples and cells and that miR-125a-5p overexpression inhibited the proliferation,migration,invasiveness and EMT of GC cells.Mechanistically,miR-125a-5p can reduce GC cell proliferation,promote E-cadherin expression,inhibit N-cadherin and vimentin expression,and reduce the EMT of GC cells,thus constraining GC cells to a certain extent.Moreover,DNMT1 inhibited miR-125a-5p expression by increasing the methylation of the miR-125a-5p promoter,thereby promoting the expression of SERPINE1,which acts together with miR-125a-5p to exert antagonistic effects on GC.CONCLUSION Our study revealed that DNMT1 promoted SERPINE1 protein expression by inducing miR-125a-5p methylation,which led to the proliferation,migration and occurrence of EMT in GC cells.展开更多
Tumor microenvironment-responsive drug self-delivery systems utilize tumor microenvironment-responsive chemical bonds to link anti-tumor drugs,exploiting the hydrophilic and hydrophobic properties of different drugs t...Tumor microenvironment-responsive drug self-delivery systems utilize tumor microenvironment-responsive chemical bonds to link anti-tumor drugs,exploiting the hydrophilic and hydrophobic properties of different drugs to form amphiphilic prodrug molecules with self-assembly characteristics.Upon stimulation by specific factors in the tumor microenvironment,these amphiphilic prodrug molecules can release drugs at precise sites within the tumor.These strategies significantly increase the drug concentration at the tumor site while effectively reducing the damage of anti-cancer drugs to normal tissues.Owing to the advanced delivery strategies such as synergistic administration and controlled drug release,tumor microenvironment-responsive drug self-delivery systems hold great potential for treating malignant tumors with multidrug resistance(MDR).At the same time,the stimulus-reactivity of metal complexes provides an important opportunity to design site-specific prodrugs that can maximize therapeutic efficacy while minimizing adverse side effects of metal drugs.This innovative drug design complements the tumor microenvironment-responsive self-delivery system,providing more feasible therapeutic strategies and possibilities in the field of cancer therapy and drug delivery.This work provides a comprehensive review of recent advancements in drug self-delivery systems,offering insights into their potential applications in cancer therapy and MDR reversal.展开更多
AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to ...AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.展开更多
Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "fac...Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.展开更多
Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone form...Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.展开更多
Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson...Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.展开更多
Walsh-Hadamard transform （WriT） can solve linear error equations on Field F2, and the method can be used to recover the parameters of convolutional code. However, solving the equations with many unknowns needs enorm...Walsh-Hadamard transform （WriT） can solve linear error equations on Field F2, and the method can be used to recover the parameters of convolutional code. However, solving the equations with many unknowns needs enormous computer memory which limits the application of WriT. In order to solve this problem, a method based on segmented WriT is proposed in this paper. The coefficient vector of high dimension is reshaped and two vectors of lower dimension are obtained. Then the WriT is operated and the requirement for computer memory is much reduced. The code rate and the constraint length of convolutional code are detected from the Walsh spectrum. And the check vector is recovered from the peak position. The validity of the method is verified by the simulation result, and the performance is proved to be optimal.展开更多
Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteob...Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor(IGF1R) in vitro. Phosphorylated PTH1R localized to the barbed ends of actin filaments and increased actin polymerization during morphological change of osteoblasts into osteocytes.Disruption of the phosphorylation site reduced actin polymerization and dendrite length. Mouse models with conditional ablation of PTH1R in osteoblasts demonstrated a reduction in the number of osteoctyes and dendrites per osteocyte, with complete overlap of PTH1R with phosphorylated-PTH1R positioning in osteocyte dendrites in wild-type mice. Thus, our findings reveal a novel signaling mechanism that enhances osteoblast-to-osteocyte transition by direct phosphorylation of PTH1R by IGF1R.展开更多
AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected...AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.展开更多
BACKGROUND: Data on the mechanical ventilation(MV) characteristics and radiologic features for the cases with H7 N9-induced ARDS were still lacking.METHODS: We describe the MV characteristics and radiologic features o...BACKGROUND: Data on the mechanical ventilation(MV) characteristics and radiologic features for the cases with H7 N9-induced ARDS were still lacking.METHODS: We describe the MV characteristics and radiologic features of adult patients with ARDS due to microbiologically confirmed H7 N9 admitted to our ICU over a 3-month period.RESULTS: Eight patients(mean age 57.38±16.75; 5 male) were diagnosed with H7 N9 in the first quarter of 2014. All developed respiratory failure complicated by acute respiratory distress syndrome(ARDS), which required MV in ICU. The baseline APACHE II and SOFA score was 11.77±6.32 and 7.71±3.12. The overall CT scores of the patients was 247.68±34.28 and the range of CT scores was 196.3–294.7. The average MV days was 14.63±6.14, and 4 patients required additional rescue therapies for refractory hypoxemia. Despite these measures, 3 patients died.CONCLUSION: In H7 N9-infected patients with ARDS, low tidal volume strategy was the conventional mode. RM as one of rescue therapies to refractory hypoxemia in these patients with serious architectural distortion and high CT scores, which could cause further lung damage, may induce bad outcomes and requires serious consideration. Prone ventilation may improve mortality, and should be performed at the early stage of the disease, not as a rescue therapy.展开更多
AIM In our previous study, we have built a nine-gene(GPC3, HGF, ANXA1, FOS, SPAG9, HSPA1 B, CXCR4, PFN1, and CALR) expression detection system based on the Ge XP system. Based on peripheral blood and Ge XP, we aimed t...AIM In our previous study, we have built a nine-gene(GPC3, HGF, ANXA1, FOS, SPAG9, HSPA1 B, CXCR4, PFN1, and CALR) expression detection system based on the Ge XP system. Based on peripheral blood and Ge XP, we aimed to analyze the results of genes expression by different multi-parameter analysis methods and build a diagnostic model to classify hepatocellular carcinoma(HCC) patients and healthy people.METHODS Logistic regression analysis, discriminant analysis, classification tree analysis, and artificial neural network were used for the multi-parameter gene expression analysis method. One hundred and three patients with early HCC and 54 age-matched healthy normal controls were used to build a diagnostic model. Fiftytwo patients with early HCC and 34 healthy people were used for validation. The area under the curve, sensitivity, and specificity were used as diagnostic indicators.RESULTS Artificial neural network of the total nine genes had the best diagnostic value, and the AUC, sensitivity, and specificity were 0.943, 98%, and 85%, respectively. At last, 52 HCC patients and 34 healthy normal controls were used for validation. The sensitivity and specificity were 96% and 86%, respectively.CONCLUSION Multi-parameter analysis methods may increase the diagnostic value compared to single factor analysis and they may be a trend of the clinical diagnosis in the future.展开更多
Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H ...Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.展开更多
The recently discovered endosulfan-degrading bacterial strain Alcaligenesfaecalis JBW4 was isolated from activated sludge. This strain is able to use endosulfan as a carbon and energy source. The optimal conditions fo...The recently discovered endosulfan-degrading bacterial strain Alcaligenesfaecalis JBW4 was isolated from activated sludge. This strain is able to use endosulfan as a carbon and energy source. The optimal conditions for the growth of strain JBW4 and for biodegradation by this strain were identified, and the metabolic products of endosulfan degradation were studied in detail. The maximum level of endosulfan biodegradation by strain JBW4 was obtained using broth at an initial pH of 7.0, an incubation temperature of 40℃ and an endosulfan concentration of I00 mg/L. The concentration of endosulfan was determined by gas chromatography. Strain JBW4 was able to degrade 87.5% of α-endosulfan and 83.9% of β-endosulfan within 5 days. These degradation rates are much higher than the previously reported bacterial strains. Endosulfan diol and endosulfan lactone were the major metabolites detected by gas chromatography-mass spectrometry; endosulfan sulfate, which is a persistent and toxic metabolite, was not detected. These results suggested that A. faecalis JBW4 degrades endosulfan via a non-oxidative pathway. The biodegradation of endosulfan by A. faecalis is reported for the first time. Additionally, the present study indicates that strain JBW4 may have potential for the biodegradation of endosulfan residues.展开更多
文摘BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.
文摘This letter responds to Wang et al's recent publication on endoscopic biliary stenting for malignant obstructive jaundice(MOJ)by offering constructive feedback and suggestions for future research.We commend the authors for their comprehensive study design and execution,which included a clear delineation of study groups and a robust set of outcome measures.We suggest that future studies incorporate additional biomarkers,such as serum levels of liver enzymes and bilirubin,to provide a more nuanced understanding of liver function changes post-intervention.The study's focus on short-term survival rates is appreciated,but we recommend exploring longer-term follow-up periods to capture the full spectrum of survival outcomes.Additionally,the inclusion of quality of life assessments using validated instruments could offer a more holistic view of patient outcomes.From a critical care perspective,we advocate for the integration of advanced imaging techniques to better characterize biliary anatomy and potentially predict treatment response or complications.We believe that incor-porating these suggestions could enhance the understanding of endoscopic biliary stenting's role in MOJ management and its impact on patient outcomes,influ-encing future clinical guidelines and practice.
基金supported in part by National Key R&D Program of China under Grant 2023YFB4705600in part by the National Natural Science Foundation of China under Grants 61925304,62127810 and 62203138+1 种基金in part by the National Postdoctoral Program for Innovative Talents under Grant BX20200107in part by the Self-Planned Task(No.SKLRS202205C)of State Key Laboratory of Robotics and System(HIT).
文摘Microscale metallic structures enhanced by additive manufacturing technology have attracted extensive attention especially in microelectronics and electromechanical devices.Meniscus-confined electrodeposition(MCED)advances microscale 3D metal printing,enabling simpler fabrication of superior metallic microstructures in air without complex equipment or post-processing.However,accurately predicting growth rates with current MCED techniques remain challenging,which is essential for precise structure fabrication and preventing nozzle clogging.In this work,we present a novel approach to electrochemical 3D printing that utilizes a self-adjusting,voxelated method for fabricating metallic microstructures.Diverging from conventional voxelated printing which focuses on monitoring voxel thickness for structure control,this technique adopts a holistic strategy.It ensures each voxel’s position is in alignment with the final structure by synchronizing the micropipette’s trajectory during deposition with the intended design,thus facilitating self-regulation of voxel position and reducing errors associated with environmental fluctuations in deposition parameters.The method’s ability to print micropillars with various tilt angles,high density,and helical arrays demonstrates its refined control over the deposition process.Transmission electron microscopy analysis reveals that the deposited structures,which are fabricated through layer-by-layer(voxel)printing,contain nanotwins that are widely known to enhance the material’s mechanical and electrical properties.Correspondingly,in situ scanning electron microscopy(SEM)microcompression tests confirm this enhancement,showing these structures exhibit a compressive yield strength exceeding 1 GPa.The indentation tests provided an average hardness of 3.71 GPa,which is the highest value reported in previous work using MCED.The resistivity measured by the four-point probe method was(1.95±0.01)×10^(−7)Ω·m,nearly 11 times that of bulk copper.These findings demonstrate the considerable advantage of this technique in fabricating complex metallic microstructures with enhanced mechanical properties,making it suitable for advanced applications in microsensors,microelectronics,and micro-electromechanical systems.
基金supported in part by the National Key R&D Program of China(Grant number 2023YFB4705600)in part by the Natural Science Foundation of Heilongjiang Province of China(Grant number YQ2024F011)in part by the Pre-research Task of State Key Laboratory of Robotics and Systems(HIT)(Grant number SKLRS202419B).
文摘Capsule Robots(CRs)with active locomotion improve on the inefficiency of passive locomotion in capsule endoscopes,showing great potential for clinical use.However,despite the development of various CR types,efficient locomotion and functional integration remain challenges due to space limitations and increasing demands.Additionally,many CRs are overly complex,so simplifying their structure while maintaining functionality is essential.This paper presents a novel magnetically actuated CR with two internal permanent magnets for oscillating locomotion and anchoring,along with a Shape Memory Alloy(SMA)-driven actuator for biopsy sampling.Compared to existing CRs,this design simplifies the structure while ensuring biopsy functionality and leaving space for a micro-CCD.The robot’s dynamics are modeled to guide its structural design and locomotion strategy.SMA characteristics are also examined to optimize the biopsy module’s parameters,improving efficiency and success rates.The CR undergoes experiments to assess safety,locomotion performance,and functionality,with results showing stable steering,and advantages in driving height,speed,and accuracy.Finally,the CR’s biopsy capabilities are validated in a gastric model and ex vivo stomach.This work offers a novel solution for gastrointestinal disease diagnosis and treatment,enhancing the application of CRs in biomedical engineering.
基金Supported by Chongqing Municipal Health and Family Planning Commission and Chongqing Municipal Science and Technology Commission Jointly Funded Key Research Projects in Traditional Chinese Medicine,No.ZY201801007。
文摘BACKGROUND Knee osteoarthritis(KOA)is a chronic condition characterized by joint pain and dysfunction,driven by aging and obesity.Research indicates that the gut microbiota significantly influences KOA,potentially affecting inflammation and disease progression through the gut-joint axis.Traditional treatments like nonsteroidal anti-inflammatory drugs offer symptom relief but have adverse effects.Emerging therapies like electroacupuncture(EA)and Tuina(TN)have shown promise in alleviating pain and improving joint function by targeting the gut microbiota.AIM To clarify the efficacy of EA with TN in treating KOA and its effect on gut microbiota regulation.METHODS Sixty patients with KOA were allocated to EA or EA+TN(ET)group(n=30 each).Seven acupoints were punctured.The ET group received TN after each EA session.Both groups completed 12 sessions.The visual analog scale(VAS)for assessing pain and the Western Ontario and McMaster Universities osteoarthritis index(WOMAC)for measuring pain intensity,joint stiffness,and functional capacity were employed to assess clinical outcomes.Pre-and post-treatment fecal specimens underwent 16S ribosomal RNA sequencing to analyze the gut microbiota.RESULTS The ET group showed higher rates of“effective”and“markedly effective”outcomes.The VAS score of the ET group remained significantly lower than that of the EA group(P<0.001)immediately after treatment and 1 week post-treatment.The total WOMAC score(P<0.001),pain(P=0.191),stiffness(P=0.015),and function scores(P<0.001)decreased significantly in the ET group post-treatment.The gut microbiota analysis revealed no significant changes in alpha diversity in either group.Beta-diversity analysis indicated distinct patterns in the ET group before and after treatment.Significant changes in microbial abundance were detected in both groups,highlighting variations in Firmicutes,Actinobacteria,Proteobacteria,and Bacteroidetes.CONCLUSION ET outperforms EA alone in improving KOA pain,stiffness,and function,potentially via gut microbiota modulation,intestinal barrier protection,and inflammation reduction.
基金the Research Program of the Science and Technology Department of Yunnan Province,No.202101AY070001-204.
文摘BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this disease.AIM To explore the mechanism of miR-125a-5p in the pathogenesis of GC.METHODS The expression levels of miR-125a-5p,SERPINE1 and DNMT1 in GC cells and tissues were detected by real-time polymerase chain reaction(PCR)and Western blotting.Methylation-specific PCR was used to detect the level of miR-125a-5p methylation.A cell counting kit 8 assay,scratch test,and a Transwell assay were performed to detect the proliferation,migration,and invasiveness of HGC27 cells,respectively.The expression of the epithelial mesenchymal transition(EMT)-related proteins E-cadherin,N-cadherin and vimentin in HGC27 cells was detected by Western blotting,while the expression of vimentin was detected by immunofluorescence.RESULTS This study revealed that miR-125a-5p was expressed at low levels in GC clinical samples and cells and that miR-125a-5p overexpression inhibited the proliferation,migration,invasiveness and EMT of GC cells.Mechanistically,miR-125a-5p can reduce GC cell proliferation,promote E-cadherin expression,inhibit N-cadherin and vimentin expression,and reduce the EMT of GC cells,thus constraining GC cells to a certain extent.Moreover,DNMT1 inhibited miR-125a-5p expression by increasing the methylation of the miR-125a-5p promoter,thereby promoting the expression of SERPINE1,which acts together with miR-125a-5p to exert antagonistic effects on GC.CONCLUSION Our study revealed that DNMT1 promoted SERPINE1 protein expression by inducing miR-125a-5p methylation,which led to the proliferation,migration and occurrence of EMT in GC cells.
基金supported by the National Natural Science Foundation of China(No.21907059)Shandong Province Chinese Medicine Science and Technology Development Project(No.M-2022258)+1 种基金the Young Scientist Development Foundation of Shandong First Medical University(No.202201-002)the Academic Promotion Program of Shandong First Medical University(Nos.2019LJ003 and 2019QL011).
文摘Tumor microenvironment-responsive drug self-delivery systems utilize tumor microenvironment-responsive chemical bonds to link anti-tumor drugs,exploiting the hydrophilic and hydrophobic properties of different drugs to form amphiphilic prodrug molecules with self-assembly characteristics.Upon stimulation by specific factors in the tumor microenvironment,these amphiphilic prodrug molecules can release drugs at precise sites within the tumor.These strategies significantly increase the drug concentration at the tumor site while effectively reducing the damage of anti-cancer drugs to normal tissues.Owing to the advanced delivery strategies such as synergistic administration and controlled drug release,tumor microenvironment-responsive drug self-delivery systems hold great potential for treating malignant tumors with multidrug resistance(MDR).At the same time,the stimulus-reactivity of metal complexes provides an important opportunity to design site-specific prodrugs that can maximize therapeutic efficacy while minimizing adverse side effects of metal drugs.This innovative drug design complements the tumor microenvironment-responsive self-delivery system,providing more feasible therapeutic strategies and possibilities in the field of cancer therapy and drug delivery.This work provides a comprehensive review of recent advancements in drug self-delivery systems,offering insights into their potential applications in cancer therapy and MDR reversal.
基金Supported by The research grants from Shanghai Municipal Science and Technology CommissionNo.114119b2900+1 种基金Shanghai Municipal Key Laboratory of Pancreatic DiseaseNo.P2012006
文摘AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.
基金supported by the National Natural Science Foundation of China (Grant nos. 81522012, 81702237, 81670807, 81871822, 81801395, 81600699, 81701383, and 81802138)the Thousand Youth Talents Plan of China (Grant no. D1119003)+8 种基金the Medicine and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences (Grant no. 2018-I2M-HL-024)the High Level Talent Gathering Project of Hunan Province (Grant nos. 2017XK2039, and 2018RS3029)the Innovation Driven Project of Central South University (Grant nos. 2016CX028,2019CX014, and 2018CX029)the Youth Foundation of Xiangya Hospital in Central South University (Grant no. 2016Q10)the Hunan Provincial Innovation Foundation for Postgraduate (Grant no. CX2018B045)the Fundamental Research Funds for the Central Universities of Central South University (Grant nos. 2017zzts211 and 2018zzts895)the Hunan Province Natural Science Foundation of China (Grant no. 2017JJ3501)the China Postdoctoral Science Foundation (Grant nos. 2017M612596, 2017M622614, and 2018M632998)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province (Grant no. 2016A030306051)
文摘Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.
文摘Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.
基金supported by the National Natural Science Foundation of China(61072120)
文摘Walsh-Hadamard transform （WriT） can solve linear error equations on Field F2, and the method can be used to recover the parameters of convolutional code. However, solving the equations with many unknowns needs enormous computer memory which limits the application of WriT. In order to solve this problem, a method based on segmented WriT is proposed in this paper. The coefficient vector of high dimension is reshaped and two vectors of lower dimension are obtained. Then the WriT is operated and the requirement for computer memory is much reduced. The code rate and the constraint length of convolutional code are detected from the Walsh spectrum. And the check vector is recovered from the peak position. The validity of the method is verified by the simulation result, and the performance is proved to be optimal.
基金provided by K01-AR060433 (T.Q.)K08-AR064833 (J.C)R01-AR063943 (X.C)
文摘Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor(IGF1R) in vitro. Phosphorylated PTH1R localized to the barbed ends of actin filaments and increased actin polymerization during morphological change of osteoblasts into osteocytes.Disruption of the phosphorylation site reduced actin polymerization and dendrite length. Mouse models with conditional ablation of PTH1R in osteoblasts demonstrated a reduction in the number of osteoctyes and dendrites per osteocyte, with complete overlap of PTH1R with phosphorylated-PTH1R positioning in osteocyte dendrites in wild-type mice. Thus, our findings reveal a novel signaling mechanism that enhances osteoblast-to-osteocyte transition by direct phosphorylation of PTH1R by IGF1R.
基金Supported by The Capital Health Development Special Scientific Research Projects,No.2014-2-2154National Natural Science Foundation of China,No.81471761 and No.81501568
文摘AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.
基金supported by the National Natural Science Foundation of China(grant number 81501654)Natural Science Foundation of Shanghai(grant number 14ZR1433700)
文摘BACKGROUND: Data on the mechanical ventilation(MV) characteristics and radiologic features for the cases with H7 N9-induced ARDS were still lacking.METHODS: We describe the MV characteristics and radiologic features of adult patients with ARDS due to microbiologically confirmed H7 N9 admitted to our ICU over a 3-month period.RESULTS: Eight patients(mean age 57.38±16.75; 5 male) were diagnosed with H7 N9 in the first quarter of 2014. All developed respiratory failure complicated by acute respiratory distress syndrome(ARDS), which required MV in ICU. The baseline APACHE II and SOFA score was 11.77±6.32 and 7.71±3.12. The overall CT scores of the patients was 247.68±34.28 and the range of CT scores was 196.3–294.7. The average MV days was 14.63±6.14, and 4 patients required additional rescue therapies for refractory hypoxemia. Despite these measures, 3 patients died.CONCLUSION: In H7 N9-infected patients with ARDS, low tidal volume strategy was the conventional mode. RM as one of rescue therapies to refractory hypoxemia in these patients with serious architectural distortion and high CT scores, which could cause further lung damage, may induce bad outcomes and requires serious consideration. Prone ventilation may improve mortality, and should be performed at the early stage of the disease, not as a rescue therapy.
基金National Key R&D Program of China,No.2016YFC0106604National Natural Science Foundation of China,No.81471761 and No.81501568
文摘AIM In our previous study, we have built a nine-gene(GPC3, HGF, ANXA1, FOS, SPAG9, HSPA1 B, CXCR4, PFN1, and CALR) expression detection system based on the Ge XP system. Based on peripheral blood and Ge XP, we aimed to analyze the results of genes expression by different multi-parameter analysis methods and build a diagnostic model to classify hepatocellular carcinoma(HCC) patients and healthy people.METHODS Logistic regression analysis, discriminant analysis, classification tree analysis, and artificial neural network were used for the multi-parameter gene expression analysis method. One hundred and three patients with early HCC and 54 age-matched healthy normal controls were used to build a diagnostic model. Fiftytwo patients with early HCC and 34 healthy people were used for validation. The area under the curve, sensitivity, and specificity were used as diagnostic indicators.RESULTS Artificial neural network of the total nine genes had the best diagnostic value, and the AUC, sensitivity, and specificity were 0.943, 98%, and 85%, respectively. At last, 52 HCC patients and 34 healthy normal controls were used for validation. The sensitivity and specificity were 96% and 86%, respectively.CONCLUSION Multi-parameter analysis methods may increase the diagnostic value compared to single factor analysis and they may be a trend of the clinical diagnosis in the future.
基金supported by the National Natural Science Foundation of China (Grant Nos.81874006,82172399,81902222,82060395,81902277,82072504,82000845)the Hunan Province Natural Science Foundation of China (Grant Nos.2020JJ4928,2020JJ4897,2021JJ30038,2021JJ40492)the Independent Exploration and Innovation Project of Central South University (Grant Nos.2020zzts255)。
文摘Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.
基金supported by the National Natural Science Foundation of China(No.21377075,41071164,21277083,40801203,41001152)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20113702110007)
文摘The recently discovered endosulfan-degrading bacterial strain Alcaligenesfaecalis JBW4 was isolated from activated sludge. This strain is able to use endosulfan as a carbon and energy source. The optimal conditions for the growth of strain JBW4 and for biodegradation by this strain were identified, and the metabolic products of endosulfan degradation were studied in detail. The maximum level of endosulfan biodegradation by strain JBW4 was obtained using broth at an initial pH of 7.0, an incubation temperature of 40℃ and an endosulfan concentration of I00 mg/L. The concentration of endosulfan was determined by gas chromatography. Strain JBW4 was able to degrade 87.5% of α-endosulfan and 83.9% of β-endosulfan within 5 days. These degradation rates are much higher than the previously reported bacterial strains. Endosulfan diol and endosulfan lactone were the major metabolites detected by gas chromatography-mass spectrometry; endosulfan sulfate, which is a persistent and toxic metabolite, was not detected. These results suggested that A. faecalis JBW4 degrades endosulfan via a non-oxidative pathway. The biodegradation of endosulfan by A. faecalis is reported for the first time. Additionally, the present study indicates that strain JBW4 may have potential for the biodegradation of endosulfan residues.
