BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombo...BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population.Several risk factors have been identified for the development of PICC-related thrombosis,including cancer type,stage,comorbidities,and catheter characteristics.Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis.AIM To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer,construct a predictive model,and validate it.METHODS Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected.Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected,and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls.A total of 255 samples were collected and used as the training set,and 77 cases were collected as the validation set in a 7:3 ratio.General patient information,case data,catheterization data,coagulation indicators,and Autar Thrombosis Risk Assessment Scale scores were analyzed.Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors,and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed statistically significant differences(P<0.05)in age,sex,Karnofsky performance status score(KPS),bedridden time,activities of daily living impairment,parenteral nutrition,catheter duration,distant metastasis,and bone marrow suppression between the thrombosis group and the non-thrombosis group.Other aspects had no statistically significant differences(P>0.05).Multivariate regression analysis showed that age≥60 years,KPS score≤50 points,parenteral nutrition,stage III to IV,distant metastasis,bone marrow suppression,and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer(P<0.05).Catheter duration of 1-6 months and catheter duration>6 months were protective factors for PICC-related thrombosis(P<0.05).The predictive model for PICC-related thrombosis was obtained as follows:P predictive probability=[exp(Logit P)]/[1+exp(Logit P)],where Logit P=age×1.907+KPS score×2.045+parenteral nutrition×9.467+catheter duration×0.506+tumor-node-metastasis(TNM)staging×2.844+distant metastasis×2.065+bone marrow suppression×2.082+activities of daily living impairment×13.926.ROC curve analysis showed an area under the curve(AUC)of 0.827(95%CI:0.724-0.929,P<0.001),with a corresponding optimal cut-off value of 0.612,sensitivity of 0.755,and specificity of 0.857.Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence(P>0.05).ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets,respectively.CONCLUSION Age,KPS score,parenteral nutrition,TNM staging,distant metastasis,bone marrow suppression,and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer,while catheter duration is a protective factor for the disease.The predictive model has an AUC of 0.827,indicating high predictive accuracy and clinical value.展开更多
Moisture-enabled electricity(ME)is a method of converting the potential energy of water in the external environment into electrical energy through the interaction of functional materials with water molecules and can b...Moisture-enabled electricity(ME)is a method of converting the potential energy of water in the external environment into electrical energy through the interaction of functional materials with water molecules and can be directly applied to energy harvesting and signal expression.However,ME can be unreliable in numerous applications due to its sluggish response to moisture,thus sacrificing the value of fast energy harvesting and highly accurate information representation.Here,by constructing a moisture-electric-moisture-sensitive(ME-MS)heterostructure,we develop an efficient ME generator with ultra-fast electric response to moisture achieved by triggering Grotthuss protons hopping in the sensitized ZnO,which modulates the heterostructure built-in interfacial potential,enables quick response(0.435 s),an unprecedented ultra-fast response rate of 972.4 mV s^(−1),and a durable electrical signal output for 8 h without any attenuation.Our research provides an efficient way to generate electricity and important insight for a deeper understanding of the mechanisms of moisture-generated carrier migration in ME generator,which has a more comprehensive working scene and can serve as a typical model for human health monitoring and smart medical electronics design.展开更多
A multitracer-gas method was proposed to study the secondary air(SA)mixing along the bed height in a circulating fluidized bed(CFB)using carbon monoxide(CO),oxygen(O_(2)),and carbon dioxide(CO_(2))as tracer gases.Expe...A multitracer-gas method was proposed to study the secondary air(SA)mixing along the bed height in a circulating fluidized bed(CFB)using carbon monoxide(CO),oxygen(O_(2)),and carbon dioxide(CO_(2))as tracer gases.Experiments were carried out on a cold CFB test rig with a cross-section of 0.42 m×0.73 m and a height of 5.50 m.The effects of superficial velocity,SA ratio,bed inventory,and particle diameter on the SA mixing were investigated.The results indicate that there are some differences in the measurement results obtained using different tracer gases,wherein the deviation between CO and CO_(2) ranges from 42%to 66%and that between O_(2) and CO_(2) ranges from 45%to 71%in the lower part of the fluidized bed.However,these differences became less pronounced as the bed height increased.Besides,the high solid concentration and fine particle diameter in the CFB may weaken the difference.The measurement results of different tracer gases show the same trends under the variation of operating parameters.Increasing superficial velocity and SA ratio and decreasing particle diameter result in better mixing of the SA.The effect of bed inventory on SA mixing is not monotonic.展开更多
Spinning disk reactor(SDR)has emerged as a novel process intensification photocatalytic reactor,and it has higher mass transfer efficiency and photon utilization for the degradation of toxic organic pollutants by adva...Spinning disk reactor(SDR)has emerged as a novel process intensification photocatalytic reactor,and it has higher mass transfer efficiency and photon utilization for the degradation of toxic organic pollutants by advanced oxidation processes(AOPs).In this study,ZnO—TiO_(2)nanocomposites were prepared by solgel method,and coated on the disk of SDR by impregnation-pull-drying-calcination method.The performance of catalyst was characterized by X-ray diffraction,scanning electron microscope,X-ray photoelectron spectroscopy,photoluminescence and ultraviolet—visible diffuse reflectance spectroscopy.Photocatalytic ozonation in SDR was used to remove phenol,and various factors on degradation effect were studied in detail.The results showed that the rate of degradation and mineralization reached 100%and 83.4%under UV light irradiation after 50 min,compared with photocatalysis and ozonation,the removal rate increased by 69.3%and 34.7%,and mineralization rate increased by 56.7%and 62.9%,which indicated that the coupling of photocatalysis and ozonation had a synergistic effect.The radical capture experiments demonstrated that the active species such as photogenerated holes(h^(+)),hydroxyl radicals(·OH),superoxide radical(·O_(2)-)were responsible for phenol degradation,and·OH played a leading role in the degradation process,while h+and·O_(2)^(-)played a non-leading role.展开更多
Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the intestinal tract,and shows a high rate of recurrence.Clinicians have accumulated extensive experience in the treatment of IBD,with biologi...Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the intestinal tract,and shows a high rate of recurrence.Clinicians have accumulated extensive experience in the treatment of IBD,with biologics and small molecule drugs having greatly expanded the therapeutic scope of IBD in recent years.Nonetheless,such treatments involve a high price and a single target of drug action.展开更多
Alveolar echinococcosis(AE)is a lethal parasitic disease caused by Echinococcus multilocularis larvae,and more than 90%of pri-mary AE lesions occur in the liver.Most of the affected individ-uals remain asymptomatic an...Alveolar echinococcosis(AE)is a lethal parasitic disease caused by Echinococcus multilocularis larvae,and more than 90%of pri-mary AE lesions occur in the liver.Most of the affected individ-uals remain asymptomatic and the disease is often diagnosed at an advanced stage.The infection may spread to organs adjacent to the liver or distant locations,eventually causing end-stage multi-ple organ AE.Brain metastasis of AE is the most fatal with an inci-dence rate of 0.2%[1].展开更多
Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy ...Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer types.Additionally,targeting POLYs therapeutically holds promise for tumor immunotherapy.展开更多
BACKGROUND The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel’s diverticulum(MD)complicated by digestive tract hemorrhage.Moreover,we aimed to evaluate th...BACKGROUND The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel’s diverticulum(MD)complicated by digestive tract hemorrhage.Moreover,we aimed to evaluate the value of double-balloon enteroscopy(DBE)in MD diagnosis and the prognosis after laparoscopic diverticula resection.AIM To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding.METHODS The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations,auxiliary examination,and follow-up after laparoscopic resection of diverticula.RESULTS(1)Among 84 MD patients complicated with hemorrhage,77 were male,and 7 were female with an average age of 31.31±10.75 years.The incidence was higher in men than in women of different ages;(2)Among the 84 MD patients,65(78.40%)had defecated dark red stools,and 50(58.80%)had no accompanying symptoms during bleeding,indicating that most MD bleeding appeared a dark red stool without accompanying symptoms;(3)The shock index of 71 patients(85.20%)was<1,suggesting that the blood loss of most MD patients was less than 20%–30%,and only a few patients had a blood loss of>30%;(4)The DBE-positive rate was 100%(54/54),99mTcpertechnetate-positive scanning rate was 78%(35/45)compared with capsule endoscopy(36%)and small intestine computed tomography(19%).These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding,especially DBE was a highly precise examination method in MD diagnosis;(5)A total of 54 MD patients with hemorrhage underwent DBE examination before surgery.DBE endoscopy revealed many mucosal manifestations including normal appearance,inflammatory changes,ulcerative changes,diverticulum inversion,and nodular hyperplasia,with ulcerative changes being the most common(53.70%).This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding;and(6)Laparoscopic dissection of diverticulae was performed in 76 patients,The patients who underwent postoperative follow-up did not experience any further bleeding.Additionally,follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding.These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis.CONCLUSION Bleeding associated with MD was predominantly observed in male adolescents,particularly at a young age.DBE was a highly precise examination method in MD diagnosis.Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.展开更多
AIM:To explore whether the subretinal transplantation of retinal progenitor cells from human embryonic stem cell-derived retinal organoid(h ERO-RPCs)could promote Müller glia dedifferentiation and transdifferenti...AIM:To explore whether the subretinal transplantation of retinal progenitor cells from human embryonic stem cell-derived retinal organoid(h ERO-RPCs)could promote Müller glia dedifferentiation and transdifferentiation,thus improving visual function and delaying retinal degenerative progression.METHODS:h ERO-RPCs were subretinally transplanted into Royal College of Surgeons(RCS)rats.Electroretinography(ERG)recording was performed at 4 and 8wk postoperation to assess retinal function.Using immunofluorescence,the changes in outer nuclear layer(ONL)thickness and retinal Müller glia were explored at 2,4,and 8wk postoperation.To verify the effect of h ERO-RPCs on Müller glia in vitro,we cocultured h ERO-RPCs with Müller glia with a Transwell system.After coculture,Ki67 staining and quantitative polymerase chain reaction(q PCR)were performed to measure the proliferation and m RNA levels of Müller glia respectively.Cell migration experiment was used to detect the effect of h ERO-RPCs on Müller glial migration.Comparisons between two groups were performed by the unpaired Student’s t-test,and comparisons among multiple groups were made with one-way ANOVA followed by Tukey’s multiple comparison test.RESULTS:The visual function and ONL thickness of RCS rats were significantly improved by transplantation of h ERO-RPCs at 4 and 8wk postoperation.In addition to inhibiting gliosis at 4 and 8wk postoperation,h ERO-RPCs significantly increased the expression of dedifferentiation-associated transcriptional factor in Müller glia and promoted the migration at 2,4 and 8wk postoperation,but not the transdifferentiation of these cells in RCS rats.In vitro,using the Transwell system,we found that h ERO-RPCs promoted the proliferation and migration of primary rat Müller glia and induced their dedifferentiation at the m RNA level.CONCLUSION:These results show that h ERO-RPCs might promote early dedifferentiation of Müller glia,which may provide novel insights into the mechanisms of stem cell therapy and Müller glial reprogramming,contributing to the development of novel therapies for retinal degeneration disorders.展开更多
Predicting the usage of container cloud resources has always been an important and challenging problem in improving the performance of cloud resource clusters.We proposed an integrated prediction method of stacking co...Predicting the usage of container cloud resources has always been an important and challenging problem in improving the performance of cloud resource clusters.We proposed an integrated prediction method of stacking container cloud resources based on variational modal decomposition(VMD)-Permutation entropy(PE)and long short-term memory(LSTM)neural network to solve the prediction difficulties caused by the non-stationarity and volatility of resource data.The variational modal decomposition algorithm decomposes the time series data of cloud resources to obtain intrinsic mode function and residual components,which solves the signal decomposition algorithm’s end-effect and modal confusion problems.The permutation entropy is used to evaluate the complexity of the intrinsic mode function,and the reconstruction based on similar entropy and low complexity is used to reduce the difficulty of modeling.Finally,we use the LSTM and stacking fusion models to predict and superimpose;the stacking integration model integrates Gradient boosting regression(GBR),Kernel ridge regression(KRR),and Elastic net regression(ENet)as primary learners,and the secondary learner adopts the kernel ridge regression method with solid generalization ability.The Amazon public data set experiment shows that compared with Holt-winters,LSTM,and Neuralprophet models,we can see that the optimization range of multiple evaluation indicators is 0.338∼1.913,0.057∼0.940,0.000∼0.017 and 1.038∼8.481 in root means square error(RMSE),mean absolute error(MAE),mean absolute percentage error(MAPE)and variance(VAR),showing its stability and better prediction accuracy.展开更多
BACKGROUND Accurate diagnosis of Helicobacter pylori(H.pylori)infection status is a crucial premise for eradication therapy,as well as evaluation of risk for gastric cancer.Recent progress on imaging enhancement endos...BACKGROUND Accurate diagnosis of Helicobacter pylori(H.pylori)infection status is a crucial premise for eradication therapy,as well as evaluation of risk for gastric cancer.Recent progress on imaging enhancement endoscopy(IEE)made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict H.pylori infection in real time.As a novel IEE modality,linked color imaging(LCI)has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone.AIM To compare the efficacy of LCI for H.pylori active infection vs conventional white light imaging(WLI).METHODS PubMed,Embase,Embase and Cochrane Library were searched up to the end of April 11,2022.The random-effects model was adopted to calculate the diagnostic efficacy of LCI and WLI.The calculation of sensitivity,specificity,and likelihood ratios were performed;symmetric receiver operator characteristic(SROC)curves and the areas under the SROC curves were computed.Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 tool.RESULTS Seven original studies were included in this study.The pooled sensitivity,specificity,positive likelihood rate,and negative likelihood rate of LCI for the diagnosis of H.pylori infection of gastric mucosa were 0.85[95%confidence interval(CI):0.76-0.92],0.82(95%CI:0.78-0.85),4.71(95%CI:3.7-5.9),and 0.18(95%CI:0.10-0.31)respectively,with diagnostic odds ratio=26(95%CI:13-52),SROC=0.87(95%CI:0.84-0.90),which showed superiority of diagnostic efficacy compared to WLI.CONCLUSION Our results showed LCI can improve efficacy of diagnosis on H.pylori infection,which represents a useful endoscopic evaluation modality for clinical practice.展开更多
For the multi-mode radar working in the modern electronicbattlefield, different working states of one single radar areprone to being classified as multiple emitters when adoptingtraditional classification methods to p...For the multi-mode radar working in the modern electronicbattlefield, different working states of one single radar areprone to being classified as multiple emitters when adoptingtraditional classification methods to process intercepted signals,which has a negative effect on signal classification. A classificationmethod based on spatial data mining is presented to address theabove challenge. Inspired by the idea of spatial data mining, theclassification method applies nuclear field to depicting the distributioninformation of pulse samples in feature space, and digs out thehidden cluster information by analyzing distribution characteristics.In addition, a membership-degree criterion to quantify the correlationamong all classes is established, which ensures classificationaccuracy of signal samples. Numerical experiments show that thepresented method can effectively prevent different working statesof multi-mode emitter from being classified as several emitters,and achieve higher classification accuracy.展开更多
目的针对反复右上腹痛的患者进行Oddi括约肌测压,以评价Oddi括约肌测压术(SOM)在慢性胆胰疾病诊治中的应用价值,并探讨内镜下十二指肠乳头切开术(EST)对Oddi括约肌基础压升高患者的疗效。方法回顾分析该院2012年10月-2014年9月30例慢性...目的针对反复右上腹痛的患者进行Oddi括约肌测压,以评价Oddi括约肌测压术(SOM)在慢性胆胰疾病诊治中的应用价值,并探讨内镜下十二指肠乳头切开术(EST)对Oddi括约肌基础压升高患者的疗效。方法回顾分析该院2012年10月-2014年9月30例慢性上腹痛疑似Oddi括约肌功能紊乱(SOD)的患者在内镜逆行胰胆管造影术(ERCP)检查时接受SOM的临床资料,观察Oddi括约肌基础压、收缩幅度、频率和传播方式。对Oddi括约肌基础压>40.0 mm Hg者及>30.0 mm Hg并存在血淀粉酶、脂肪酶、谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(AKP)升高超过正常值2倍以上和(或)胆总管、胰管管增宽者行EST治疗,并随访其疗效。结果 30例患者SOM均存在不同程度的异常,Oddi括约肌基础压力为(36.6±21.1)mm Hg,收缩幅度为(210.6±25.7)mm Hg,收缩频率为(10.1±3.1)次/min,逆向收缩率为(55.0±8.0)%。30例患者均接受EST治疗,术后随访,其中27例(90.0%)有效。结论 SOM助于评价Oddi括约肌功能,对诊断SOD具有较大价值,测压发现Oddi括约肌基础压升高患者EST治疗可获得满意疗效。展开更多
Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endop...Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal(1 mg/kg), by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.展开更多
AIM: To identify the possible predictors of early complications after the initial intervention in acute necrotizing pancreatitis.METHODS: We collected the medical records of 334 patients with acute necrotizing pancrea...AIM: To identify the possible predictors of early complications after the initial intervention in acute necrotizing pancreatitis.METHODS: We collected the medical records of 334 patients with acute necrotizing pancreatitis who received initial intervention in our center. Complications associated with predictors were analyzed.RESULTS: The postoperative mortality rate was 16% (53/334). Up to 31% of patients were successfully treated with percutaneous catheter drainage alone. The rates of intra-abdominal bleeding, colonic fistula, and progressive infection were 15% (50/334), 20% (68/334), and 26% (87/334), respectively. Multivariate analysis indicated that Marshall score upon admission, multiple organ failure, preoperative respiratory infection, and sepsis were the predictors of postoperative progressive infection (P < 0.05). Single organ failure, systemic inflammatory response syndrome upon admission, and C-reactive protein level upon admission were the risk factors of postoperative colonic fistula (P < 0.05). Moreover, preoperative Marshall score, organ failure, sepsis, and preoperative systemic inflammatory response syndrome were the risk factors of postoperative intra-abdominal bleeding (P < 0.05).CONCLUSION: Marshall score, organ failures, preoperative respiratory infection, sepsis, preoperative systemic inflammatory response syndrome, and C-reactive protein level upon admission are associated with postoperative complications.展开更多
Rheumatoid arthritis(RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A...Rheumatoid arthritis(RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages:(i) triggering,(ii) maturation,(iii) targeting, and(iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies(including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.展开更多
文摘BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population.Several risk factors have been identified for the development of PICC-related thrombosis,including cancer type,stage,comorbidities,and catheter characteristics.Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis.AIM To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer,construct a predictive model,and validate it.METHODS Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected.Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected,and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls.A total of 255 samples were collected and used as the training set,and 77 cases were collected as the validation set in a 7:3 ratio.General patient information,case data,catheterization data,coagulation indicators,and Autar Thrombosis Risk Assessment Scale scores were analyzed.Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors,and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed statistically significant differences(P<0.05)in age,sex,Karnofsky performance status score(KPS),bedridden time,activities of daily living impairment,parenteral nutrition,catheter duration,distant metastasis,and bone marrow suppression between the thrombosis group and the non-thrombosis group.Other aspects had no statistically significant differences(P>0.05).Multivariate regression analysis showed that age≥60 years,KPS score≤50 points,parenteral nutrition,stage III to IV,distant metastasis,bone marrow suppression,and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer(P<0.05).Catheter duration of 1-6 months and catheter duration>6 months were protective factors for PICC-related thrombosis(P<0.05).The predictive model for PICC-related thrombosis was obtained as follows:P predictive probability=[exp(Logit P)]/[1+exp(Logit P)],where Logit P=age×1.907+KPS score×2.045+parenteral nutrition×9.467+catheter duration×0.506+tumor-node-metastasis(TNM)staging×2.844+distant metastasis×2.065+bone marrow suppression×2.082+activities of daily living impairment×13.926.ROC curve analysis showed an area under the curve(AUC)of 0.827(95%CI:0.724-0.929,P<0.001),with a corresponding optimal cut-off value of 0.612,sensitivity of 0.755,and specificity of 0.857.Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence(P>0.05).ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets,respectively.CONCLUSION Age,KPS score,parenteral nutrition,TNM staging,distant metastasis,bone marrow suppression,and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer,while catheter duration is a protective factor for the disease.The predictive model has an AUC of 0.827,indicating high predictive accuracy and clinical value.
基金the Natural Science Foundation of Beijing Municipality(2222075)National Natural Science Foundation of China(22279010,21671020,51673026)Analysis&Testing Center,Beijing Institute of Technology.
文摘Moisture-enabled electricity(ME)is a method of converting the potential energy of water in the external environment into electrical energy through the interaction of functional materials with water molecules and can be directly applied to energy harvesting and signal expression.However,ME can be unreliable in numerous applications due to its sluggish response to moisture,thus sacrificing the value of fast energy harvesting and highly accurate information representation.Here,by constructing a moisture-electric-moisture-sensitive(ME-MS)heterostructure,we develop an efficient ME generator with ultra-fast electric response to moisture achieved by triggering Grotthuss protons hopping in the sensitized ZnO,which modulates the heterostructure built-in interfacial potential,enables quick response(0.435 s),an unprecedented ultra-fast response rate of 972.4 mV s^(−1),and a durable electrical signal output for 8 h without any attenuation.Our research provides an efficient way to generate electricity and important insight for a deeper understanding of the mechanisms of moisture-generated carrier migration in ME generator,which has a more comprehensive working scene and can serve as a typical model for human health monitoring and smart medical electronics design.
基金the Key Project of the National Research Program of China(2020YFB0606201)。
文摘A multitracer-gas method was proposed to study the secondary air(SA)mixing along the bed height in a circulating fluidized bed(CFB)using carbon monoxide(CO),oxygen(O_(2)),and carbon dioxide(CO_(2))as tracer gases.Experiments were carried out on a cold CFB test rig with a cross-section of 0.42 m×0.73 m and a height of 5.50 m.The effects of superficial velocity,SA ratio,bed inventory,and particle diameter on the SA mixing were investigated.The results indicate that there are some differences in the measurement results obtained using different tracer gases,wherein the deviation between CO and CO_(2) ranges from 42%to 66%and that between O_(2) and CO_(2) ranges from 45%to 71%in the lower part of the fluidized bed.However,these differences became less pronounced as the bed height increased.Besides,the high solid concentration and fine particle diameter in the CFB may weaken the difference.The measurement results of different tracer gases show the same trends under the variation of operating parameters.Increasing superficial velocity and SA ratio and decreasing particle diameter result in better mixing of the SA.The effect of bed inventory on SA mixing is not monotonic.
基金supported by the National Natural Science Foundation of China(22208328)Fundamental Research Program of Shanxi Province(20210302124618,202203021212134)。
文摘Spinning disk reactor(SDR)has emerged as a novel process intensification photocatalytic reactor,and it has higher mass transfer efficiency and photon utilization for the degradation of toxic organic pollutants by advanced oxidation processes(AOPs).In this study,ZnO—TiO_(2)nanocomposites were prepared by solgel method,and coated on the disk of SDR by impregnation-pull-drying-calcination method.The performance of catalyst was characterized by X-ray diffraction,scanning electron microscope,X-ray photoelectron spectroscopy,photoluminescence and ultraviolet—visible diffuse reflectance spectroscopy.Photocatalytic ozonation in SDR was used to remove phenol,and various factors on degradation effect were studied in detail.The results showed that the rate of degradation and mineralization reached 100%and 83.4%under UV light irradiation after 50 min,compared with photocatalysis and ozonation,the removal rate increased by 69.3%and 34.7%,and mineralization rate increased by 56.7%and 62.9%,which indicated that the coupling of photocatalysis and ozonation had a synergistic effect.The radical capture experiments demonstrated that the active species such as photogenerated holes(h^(+)),hydroxyl radicals(·OH),superoxide radical(·O_(2)-)were responsible for phenol degradation,and·OH played a leading role in the degradation process,while h+and·O_(2)^(-)played a non-leading role.
基金Yunnan Digestive Endoscopy Clinical Medical Center Foundation[2X2019-01-02]for Health Commission of Yunnan[2022LCZXKF-XH13,2022LCZXKF-XH15 and 2022LCZXKF-XH19]Fundamental Research Projects of Yunnan Province[202201AU070013]。
文摘Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the intestinal tract,and shows a high rate of recurrence.Clinicians have accumulated extensive experience in the treatment of IBD,with biologics and small molecule drugs having greatly expanded the therapeutic scope of IBD in recent years.Nonetheless,such treatments involve a high price and a single target of drug action.
基金This study was supported by the grants from the National Natural Science Foundation of China(81960377)Open Project of State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia(SKL-HIDCA-2020-BC and SKL-HIDCA-2021-4)Xinjiang Uygur Autonomous Region University Scientific Research Project(XJEDU2021I016).
文摘Alveolar echinococcosis(AE)is a lethal parasitic disease caused by Echinococcus multilocularis larvae,and more than 90%of pri-mary AE lesions occur in the liver.Most of the affected individ-uals remain asymptomatic and the disease is often diagnosed at an advanced stage.The infection may spread to organs adjacent to the liver or distant locations,eventually causing end-stage multi-ple organ AE.Brain metastasis of AE is the most fatal with an inci-dence rate of 0.2%[1].
基金supported by the project of funds by the Consultation of Provincial Department and University for S&T Innovation granted by Hebei Provincial Department of Science and Technology and Hebei Medical University(2020TXZH04).
文摘Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer types.Additionally,targeting POLYs therapeutically holds promise for tumor immunotherapy.
基金Supported by the Ten Thousand Doctor Plan in Yunnan Province,No.YNWR-MY-2018-020Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province,No.2021LCZXXF-XH07,No.2021LCZXXF-XH15,and No.2022LCZXKF-XH17Yunnan Provincial Key Laboratory of Clinical Virology,No.202205AG070053-07.
文摘BACKGROUND The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel’s diverticulum(MD)complicated by digestive tract hemorrhage.Moreover,we aimed to evaluate the value of double-balloon enteroscopy(DBE)in MD diagnosis and the prognosis after laparoscopic diverticula resection.AIM To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding.METHODS The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations,auxiliary examination,and follow-up after laparoscopic resection of diverticula.RESULTS(1)Among 84 MD patients complicated with hemorrhage,77 were male,and 7 were female with an average age of 31.31±10.75 years.The incidence was higher in men than in women of different ages;(2)Among the 84 MD patients,65(78.40%)had defecated dark red stools,and 50(58.80%)had no accompanying symptoms during bleeding,indicating that most MD bleeding appeared a dark red stool without accompanying symptoms;(3)The shock index of 71 patients(85.20%)was<1,suggesting that the blood loss of most MD patients was less than 20%–30%,and only a few patients had a blood loss of>30%;(4)The DBE-positive rate was 100%(54/54),99mTcpertechnetate-positive scanning rate was 78%(35/45)compared with capsule endoscopy(36%)and small intestine computed tomography(19%).These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding,especially DBE was a highly precise examination method in MD diagnosis;(5)A total of 54 MD patients with hemorrhage underwent DBE examination before surgery.DBE endoscopy revealed many mucosal manifestations including normal appearance,inflammatory changes,ulcerative changes,diverticulum inversion,and nodular hyperplasia,with ulcerative changes being the most common(53.70%).This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding;and(6)Laparoscopic dissection of diverticulae was performed in 76 patients,The patients who underwent postoperative follow-up did not experience any further bleeding.Additionally,follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding.These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis.CONCLUSION Bleeding associated with MD was predominantly observed in male adolescents,particularly at a young age.DBE was a highly precise examination method in MD diagnosis.Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.
基金Supported by the National Key Research and Development Program of China(No.2018YFA0107302)the Natural Science Foundation of Chongqing,China(No.cstc2021jcyj-msxm X0437)。
文摘AIM:To explore whether the subretinal transplantation of retinal progenitor cells from human embryonic stem cell-derived retinal organoid(h ERO-RPCs)could promote Müller glia dedifferentiation and transdifferentiation,thus improving visual function and delaying retinal degenerative progression.METHODS:h ERO-RPCs were subretinally transplanted into Royal College of Surgeons(RCS)rats.Electroretinography(ERG)recording was performed at 4 and 8wk postoperation to assess retinal function.Using immunofluorescence,the changes in outer nuclear layer(ONL)thickness and retinal Müller glia were explored at 2,4,and 8wk postoperation.To verify the effect of h ERO-RPCs on Müller glia in vitro,we cocultured h ERO-RPCs with Müller glia with a Transwell system.After coculture,Ki67 staining and quantitative polymerase chain reaction(q PCR)were performed to measure the proliferation and m RNA levels of Müller glia respectively.Cell migration experiment was used to detect the effect of h ERO-RPCs on Müller glial migration.Comparisons between two groups were performed by the unpaired Student’s t-test,and comparisons among multiple groups were made with one-way ANOVA followed by Tukey’s multiple comparison test.RESULTS:The visual function and ONL thickness of RCS rats were significantly improved by transplantation of h ERO-RPCs at 4 and 8wk postoperation.In addition to inhibiting gliosis at 4 and 8wk postoperation,h ERO-RPCs significantly increased the expression of dedifferentiation-associated transcriptional factor in Müller glia and promoted the migration at 2,4 and 8wk postoperation,but not the transdifferentiation of these cells in RCS rats.In vitro,using the Transwell system,we found that h ERO-RPCs promoted the proliferation and migration of primary rat Müller glia and induced their dedifferentiation at the m RNA level.CONCLUSION:These results show that h ERO-RPCs might promote early dedifferentiation of Müller glia,which may provide novel insights into the mechanisms of stem cell therapy and Müller glial reprogramming,contributing to the development of novel therapies for retinal degeneration disorders.
基金The National Natural Science Foundation of China (No.62262011)The Natural Science Foundation of Guangxi (No.2021JJA170130).
文摘Predicting the usage of container cloud resources has always been an important and challenging problem in improving the performance of cloud resource clusters.We proposed an integrated prediction method of stacking container cloud resources based on variational modal decomposition(VMD)-Permutation entropy(PE)and long short-term memory(LSTM)neural network to solve the prediction difficulties caused by the non-stationarity and volatility of resource data.The variational modal decomposition algorithm decomposes the time series data of cloud resources to obtain intrinsic mode function and residual components,which solves the signal decomposition algorithm’s end-effect and modal confusion problems.The permutation entropy is used to evaluate the complexity of the intrinsic mode function,and the reconstruction based on similar entropy and low complexity is used to reduce the difficulty of modeling.Finally,we use the LSTM and stacking fusion models to predict and superimpose;the stacking integration model integrates Gradient boosting regression(GBR),Kernel ridge regression(KRR),and Elastic net regression(ENet)as primary learners,and the secondary learner adopts the kernel ridge regression method with solid generalization ability.The Amazon public data set experiment shows that compared with Holt-winters,LSTM,and Neuralprophet models,we can see that the optimization range of multiple evaluation indicators is 0.338∼1.913,0.057∼0.940,0.000∼0.017 and 1.038∼8.481 in root means square error(RMSE),mean absolute error(MAE),mean absolute percentage error(MAPE)and variance(VAR),showing its stability and better prediction accuracy.
基金Clinical Medical Center of Yunnan Provincial Health Commission,No.2020LCZXKF-XH05 and 2021LCZXXF-XH03Young Academic Talents Cultivation Program of Yunnan Province,No.202205AC160070.
文摘BACKGROUND Accurate diagnosis of Helicobacter pylori(H.pylori)infection status is a crucial premise for eradication therapy,as well as evaluation of risk for gastric cancer.Recent progress on imaging enhancement endoscopy(IEE)made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict H.pylori infection in real time.As a novel IEE modality,linked color imaging(LCI)has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone.AIM To compare the efficacy of LCI for H.pylori active infection vs conventional white light imaging(WLI).METHODS PubMed,Embase,Embase and Cochrane Library were searched up to the end of April 11,2022.The random-effects model was adopted to calculate the diagnostic efficacy of LCI and WLI.The calculation of sensitivity,specificity,and likelihood ratios were performed;symmetric receiver operator characteristic(SROC)curves and the areas under the SROC curves were computed.Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 tool.RESULTS Seven original studies were included in this study.The pooled sensitivity,specificity,positive likelihood rate,and negative likelihood rate of LCI for the diagnosis of H.pylori infection of gastric mucosa were 0.85[95%confidence interval(CI):0.76-0.92],0.82(95%CI:0.78-0.85),4.71(95%CI:3.7-5.9),and 0.18(95%CI:0.10-0.31)respectively,with diagnostic odds ratio=26(95%CI:13-52),SROC=0.87(95%CI:0.84-0.90),which showed superiority of diagnostic efficacy compared to WLI.CONCLUSION Our results showed LCI can improve efficacy of diagnosis on H.pylori infection,which represents a useful endoscopic evaluation modality for clinical practice.
基金supported by the National Natural Science Foundation of China(61371172)the International S&T Cooperation Program of China(2015DFR10220)+1 种基金the Ocean Engineering Project of National Key Laboratory Foundation(1213)the Fundamental Research Funds for the Central Universities(HEUCF1608)
文摘For the multi-mode radar working in the modern electronicbattlefield, different working states of one single radar areprone to being classified as multiple emitters when adoptingtraditional classification methods to process intercepted signals,which has a negative effect on signal classification. A classificationmethod based on spatial data mining is presented to address theabove challenge. Inspired by the idea of spatial data mining, theclassification method applies nuclear field to depicting the distributioninformation of pulse samples in feature space, and digs out thehidden cluster information by analyzing distribution characteristics.In addition, a membership-degree criterion to quantify the correlationamong all classes is established, which ensures classificationaccuracy of signal samples. Numerical experiments show that thepresented method can effectively prevent different working statesof multi-mode emitter from being classified as several emitters,and achieve higher classification accuracy.
文摘目的针对反复右上腹痛的患者进行Oddi括约肌测压,以评价Oddi括约肌测压术(SOM)在慢性胆胰疾病诊治中的应用价值,并探讨内镜下十二指肠乳头切开术(EST)对Oddi括约肌基础压升高患者的疗效。方法回顾分析该院2012年10月-2014年9月30例慢性上腹痛疑似Oddi括约肌功能紊乱(SOD)的患者在内镜逆行胰胆管造影术(ERCP)检查时接受SOM的临床资料,观察Oddi括约肌基础压、收缩幅度、频率和传播方式。对Oddi括约肌基础压>40.0 mm Hg者及>30.0 mm Hg并存在血淀粉酶、脂肪酶、谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(AKP)升高超过正常值2倍以上和(或)胆总管、胰管管增宽者行EST治疗,并随访其疗效。结果 30例患者SOM均存在不同程度的异常,Oddi括约肌基础压力为(36.6±21.1)mm Hg,收缩幅度为(210.6±25.7)mm Hg,收缩频率为(10.1±3.1)次/min,逆向收缩率为(55.0±8.0)%。30例患者均接受EST治疗,术后随访,其中27例(90.0%)有效。结论 SOM助于评价Oddi括约肌功能,对诊断SOD具有较大价值,测压发现Oddi括约肌基础压升高患者EST治疗可获得满意疗效。
文摘Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal(1 mg/kg), by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.
文摘AIM: To identify the possible predictors of early complications after the initial intervention in acute necrotizing pancreatitis.METHODS: We collected the medical records of 334 patients with acute necrotizing pancreatitis who received initial intervention in our center. Complications associated with predictors were analyzed.RESULTS: The postoperative mortality rate was 16% (53/334). Up to 31% of patients were successfully treated with percutaneous catheter drainage alone. The rates of intra-abdominal bleeding, colonic fistula, and progressive infection were 15% (50/334), 20% (68/334), and 26% (87/334), respectively. Multivariate analysis indicated that Marshall score upon admission, multiple organ failure, preoperative respiratory infection, and sepsis were the predictors of postoperative progressive infection (P < 0.05). Single organ failure, systemic inflammatory response syndrome upon admission, and C-reactive protein level upon admission were the risk factors of postoperative colonic fistula (P < 0.05). Moreover, preoperative Marshall score, organ failure, sepsis, and preoperative systemic inflammatory response syndrome were the risk factors of postoperative intra-abdominal bleeding (P < 0.05).CONCLUSION: Marshall score, organ failures, preoperative respiratory infection, sepsis, preoperative systemic inflammatory response syndrome, and C-reactive protein level upon admission are associated with postoperative complications.
基金supported in part by the Australian National Health and Medical Research Council (NHMRC, No. 1107828)Arthritis foundation of Australiathe University of Western Australia Research Collaboration Awards
文摘Rheumatoid arthritis(RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages:(i) triggering,(ii) maturation,(iii) targeting, and(iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies(including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.