A robust,selective and highly sensitive chemiluminescent (CL) platform for protein assay was presented in this paper.This novel CL approach utilized rolling circle amplification (RCA) as a signal enhancement technique and the 96-well plate as the immobilization and separation carrier.Typically,the antibody immobilized on the surface of 96-well plate was sandwiched with the protein target and the aptamer-primer sequence.This aptamer-primer sequence was then employed as the primer of RCA.Based on this design,a number of the biotinylated probes and streptavidin-horseradish peroxidase (SA-HRP) were captured on the plate,and the CL signal was amplified.In summary,our results demonstrated a robust biosensor with a detection limit of 10 fM that is easy to be established and utilized,and devoid of light source.Therefore,this new technique will broaden the perspective for future development of DNA-based biosensors for the detection of other protein biomarkers related to clinical diseases,by taking advantages of high sensitivity and selectivity.

Maturity-onset diabetes of the young (MODY)is a heterogeneous monogenic diabetes, in which MODY1, MODY2, and MODY3 are the most common subtypes. In recent years, new hypoglycemic drugs such as glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and glucokinase activators (GKA)have made good progress in the treatment of diabetes. Based on the latest basic and clinical evidence, the article reviews the pathogenesis, clinical features, diagnosis and treatment progress of new hypoglycemic drugs of the above three types of MODY, aiming to develop safer and more effective new ways for the diagnosis and treatment of MODY.

A robust, selective and highly sensitive chemiluminescent （CL） platform for protein assay was presented in this paper. This novel CL approach utilized rolling circle amplification （RCA） as a signal enhancement technique and the 96-well plate as the immobilization and separation carrier. Typically, the antibody immobilized on the surface of 96-well plate was sandwiched with the protein target and the aptamer-primer sequence. This aptamer-primer sequence was then employed as the primer of RCA. Based on this design, a number of the biotinylated probes and streptavidin-horseradish peroxidase （SA-HRP） were captured on the plate, and the CL signal was amplified. In summary, our results demonstrated a robust biosensor with a detection limit of 10 fM that is easy to be established and utilized, and devoid of light source. Therefore, this new technique .will broaden the perspective for future development of DNA-based biosensors for the detection of other protein biomarkers related to clinical diseases, by taking advantages of high sensitivity and selectivity.

Objective ToexploretheMRIfeaturesanddifferentialdiagnosisofgemistocyticastrocytoma(GemA).Methods The MRIfeaturesof10casesofGemAprovedbysurgeryandpathologywereinvestigatedretrospectively(thelocationoftumor,tumor shape,boundary,signalandenhancement)andtheliteraturewasreviewed.Results All10casesofGemA weresupratentorialand solitary.Ofthese10cases,7caseswerelocatedinthefrontallobe,5casesinthetemporallobe,6casesinmultiplelobesandinvaded theoppositebraintissuesthroughcorpuscallosum.8casesweresolidGcystic,8casespresentedwithunclearboundary,only2cases hadclearboundary.Therewasnoedemaormildedemain7casesandobviousedemain3cases.Thesolidpartoftumorswereisointense orslighthypointenseonT1WI,only1caseshowedhighintensityonT1WI,isointenseorslighthyperintenseonT2WI.CTsuggested calcificationin2cases.6casesweremildlyenhanced,4casesweremarkedlyenhanced.MRSshowed(n＝4)thatCHopeakwasmildly ormoderatelyincreased,NAApeakwassignificantlyreduced,theaverageratioofCho/NAA was2.91.DWIshowedhyperintenseor slighthyperintense(n＝3),theADCaveragevalueoftumorROIwasabout(1.150±0.081)×10－3 mm2/s.1caseofSWIsequence showedthickeningandcircuitousvascularshadow.Conclusion AsMRIofGemAischaracterizedbyhighandlowgradegliomas,the preoperativediagnosisisdifficult.Combiningenhancementwithfunctionalexamination,itisexpectedtoimprovetheaccuracyofpreoperative diagnosisofGemA.

Objective To explore the MRI findings of diffuse midline gliomas with H3K27M mutation, and help us understand this new entity and improve the accuracy of diagnosis. Methods The clinical and imaging data of 17 diffuse midline gliomas with H3K27M mutation confirmed by pathology were retrospectively collected from July 2016 to April 2018 in Guangdong Sanjiu Brain Hospital. All patients were performed with pre?contrast and post?contrast MRI examination. All images were analyzed according to the location, shape, boundary, solid or cystic, signal feature, enhancement feature, and degree of edema. Results (1) Location:Six cases located in thalamus,4 cases located in brainstem,1 located in hypothalamus, 6 cases had multiple lesions in the midline and/or involving one or more brain. (2) Morphology and boundary:Seven cases had regular shape and clear boundary, 10 cases had irregular shapes and unclear boundaries. (3) Necrosis, cystic degeneration, hemorrhage: Twelve cases had necrosis or cystic degeneration in varying degree, 4 cases had hemorrhage. (4) Signal and enhancement features: The solid component showed slightly?low or low signal on T1WI, and slightly?high or high signal on T2WI; the cystic component showed obvious low signal on T1WI and obvious high signal on T2WI. T1WI enhancement:Eight cases showed uneven light?moderate enhancements, and all cases were adults; Six cases showed significant enhancements with large or small rings; Three cases showed uneven obvious enhancement. (5) Peritumoral edema: Fourteen cases had mild peritumoral edema,1 case had moderate peritumoral edema,2 cases had obvious peritumoral edema. Conclusion The MRI findings of diffuse midline gliomas with H3K27M mutation had certain characteristics,which can help to improve the level of diagnosis and differential diagnosis.

Objective:To analyze the global incidence and mortality of cancer from 1990 to 2019.Methods:The Global Burden of Disease Study 2019 (GBD2019) database was utilized to analyze the global incidence and mortality of cancer, the order of incidence and mortality of cancer, the incidence and mortality of different age groups, and the trend of incidence and mortality from 1990 to 2019. Standardized incidence and mortality rates were derived by utilizing the world standard population age structure.Results:In 1990, global cancer cases numbered 10.295 9 million with an incidence rate of 192.45/100 000, leading to 5.732 6 million deaths and a mortality rate of 107.16/100 000. While in 2019, global cancer cases escalated to 23.568 5 million with an incidence rate of 304.60/100 000, resulting in 10.022 8 million deaths and a mortality rate of 129.54/100 000, all higher than those in 1990. In 2019, lung cancer showed the highest incidence rate of both sexes combined in the world (29.21/100 000), followed by colorectal cancer, breast cancer, prostate cancer and gastric cancer. The incidence of lung cancer was highest among males (39.24/100 000), while the incidence of breast cancer was highest among females (51.27/100 000). Lung cancer also had the highest mortality rate worldwide in both sexes combined (26.40/100 000), followed by colorectal cancer, gastric cancer, breast cancer and pancreatic cancer. Lung cancer had the highest mortality among males (35.72/100 000), while breast cancer had the highest mortality among females (17.85/100 000). In 2019, the global cancer incidence rate showed an upward trend with age. The incidence rate was low before the age of 25, and increased rapidly after the age of 25. The incidence rates of both sexes combined, males and females all reached the peak in the age group of over 85 years old, which were 3 084.18/100 000, 4 434.81/100 000 and 2 353.07/100 000 respectively; The incidence rate of females in the age group of 20-50 years old was higher than that of males, but the incidence rate of males in the age group of over 55 years old was higher than that of females. Compared with 1990, the incidence rates of both sexes combined in the age group of over 20, of males over 55 years old, as well as of females over 15 years old, were all higher than those in 2019. In 2019, the global tumor mortality rate showed an upward trend with age. The mortality rate was relatively low before the age of 35, and increased rapidly after the age of 35. The mortality rates for both sexes combined, as well as for males and females, reached the peak in the age group of over 85 years old, which were 1 787.84/100 000, 2 509.87/100 000, and 1 369.99/100 000 respectively; The mortality rate of females in the age group of 20-40 years old was higher than that of males, and the mortality rate of males in the age group of over 45 years old was higher than that of females; For the age of 0-80 years old, the mortality rates for both sexes combined, males, and females were lower in 2019 than 1990, but higher in the age of 85 years old and above. The global standardized incidence rate of cancer showed an overall upward trend, with an average annual increase of 0.30% from 1990 to 2019. The global standardized mortality rate of cancer showed an overall downward trend, with an average annual decrease of 0.60% from 1990 to 2019.Conclusion:From 1990 to 2019, the global standardized incidence rate of cancers shows an overall upward trend, while the global standardized mortality rate of cancers has an overall downward trend, and the global incidence and mortality rate of cancers increases with age. The global burden of cancer disease is still heavy. Lung cancer is the cancer with the highest incidence and mortality rate in the world. The highest incidence rate is lung cancer among males, and breast cancer among females. Different countries or regions need to take corresponding cancer prevention and treatment strategies according to their actual conditions.

Objective:To investigate the predictive value of preoperative D-dimer level for futile recanalization (FR) after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS).Methods:It was a nested case-control study. A total of 116 patients with large vessel occlusion (LVO) stroke, who underwent successful recanalization (modified Thrombolysis in Cerebral Infarction, mTICI≥2b) after MT at the Stroke Unit of Beijing Hospital from August 2018 to January 2022,were consecutively enrolled, including 72 males (62.1%) with the age of (72.8±13.1) years. According to the 3-month modified Rankin Scale (mRS) score after MT, patients were divided into the meaningful recanalization group (mRS 0-2, n=41) and the futile recanalization group (mRS 3-6, n=75). The baseline clinical data of enrolled patients was collected. Logistic regression analysis was used to identify the independent risk factors for FR after MT in patients with AIS. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer for FR. Results:Multivariate logistic regression analysis showed that high baseline systolic blood pressure (SBP) ( OR=1.038, 95% CI: 1.012-1.065, P=0.004), baseline National Institutes of Health Stroke Scale (NIHSS) score≥12 ( OR=10.157, 95% CI: 3.624-28.470, P<0.001) and high preoperative D-dimer level ( OR=4.536, 95% CI: 1.379-14.922, P=0.013) were independent predictors of FR after MT in AIS patients with LVO. ROC curve analysis indicated a good predictive value of preoperative D-dimer for the occurrence of FR ( AUC=0.733, 95% CI: 0.638-0.829, P<0.05), the optimal cut-off value of D-dimer was 2.65 μg/L(Lg), with the Youden index, sensitivity, specificity and accuracy of 0.435, 53.3%, 90.2% and 66.4%, respectively. Conclusion:High preoperative D-dimer level is an independent predictor of futile recanalization after MT in AIS patients with LVO, which shows good predictive ability for futile recanalization.

Osteoporosis is a chronic skeletal disease characterized by low bone mass， destruction of bone tissue microarchitecture， and imbalance of bone homeostasis， leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species （ROS） and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen， carbon monoxide， and free iron. The metabolites can scavenge ROS， thereby exerting an antioxidant effect in cells. At present， domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target， multi-channel， and multi-level advantages. Chinese medicine can resist oxidative stress， inflammatory response， and apoptosis by regulating the Nrf2/HO-1 signaling pathway， thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis， to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time， a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted， to provide a theoretical basis for further precise treatment of osteoporosis.

The impairment of islets β cell by autoimmune response is an important cause of type 1 diabetes mellitus (T1DM). Some monogenic autoimmune syndromes could induce T1DM in difference chance, which are important disease models to deeply understand autoimmunity and T1DM. This article reviews the diagnosis, treatment and genetic detection of eight known single gene autoimmune syndromes associated with T1DM, arming to expand the diagnosis and treatment of T1DM.

Intervertebral disc degeneration is one of the common causes of chronic low back pain. As a common spinal disease， its clinical symptoms are mainly low back pain and limited function， which seriously affects physical and psychological health. Because of its complex and unclear pathogenesis， the treatment of intervertebral disc degeneration has been the focus of scientific researchers and clinical workers. At present， the treatment of intervertebral disc degeneration mainly includes non-surgical therapy and surgical therapy， which can alleviate the clinical symptoms of patients to a certain extent， but easily induce new complications， and it is difficult to restore the normal physiological function of the intervertebral disc. In recent years， along with the advanced research on matrix metalloproteinases （MMPs） in the tissues of intervertebral disc degeneration， it has been found that MMPs can be used as molecular therapeutic targets. The expression of MMPs in the intervertebral disc tissues can be regulated by reducing the content and composition of the extracellular matrix of the intervertebral disc， so as to slow down intervertebral disc degeneration and even reverse the occurrence of intervertebral disc degeneration. This treatment is expected to delay intervertebral disc degeneration caused by changes in extracellular matrix composition or content. In recent years， with the continuous development of network pharmacology and bioinformatics research， a large number of researchers have explored the treatment of intervertebral disc degeneration by traditional Chinese medicine （TCM） and found that TCM can reduce the degradation of extracellular matrix by inhibiting the expression of MMPs， thus alleviating the symptoms of intervertebral disc degeneration and slowing down the progression of intervertebral disc degeneration. This paper reviewed the research progress of TCM intervention in MMP expression in the treatment of intervertebral disc degeneration， aiming at providing references for the application of TCM in the prevention and treatment of intervertebral disc degeneration.