Research progress on the relationship between m6A methylation modification and acute kidney injury / 实用医学杂志

Acute kidney injury(AKI)is a global public health problem with high morbidity,high mortality and costly treatment cost.The pathogenesis of AKI is very complex,and the treatment strategies for AKI are lim-ited,then it is very matter to explore the pathophysiological mechanism and potential therapeutic targets of acute kidney injury.N6-methyladenosine(m6A)is the most abundant and extremely conservative epigenetic modification in eukaryotic,which is a dynamic and reversible process involving in splicing,nuclear export,translation,stabil-ity,and higher structure of RNA,and regulated by three regulatory factors:methyltransferase,demethylase and methylated reading protein.Current studies have found that m6A plays an important regulatory role in AKI and can be a potential therapeutic target for AKI.In this review,we provide a brief description of m6A and summarize the impact of m6A on AKI and possible future study directions for this research.

Characteristics of cerebral cortex activation in different swallowing periods based on near-infrared spectroscopy / 中国康复理论与实践

ObjectiveTo explore the cerebral cortex activation in different swallowing periods using functional near-infrared spectroscopy (fNIRS). MethodsFrom October to December 2023, a total of 18 healthy adults were recruited to perform four tasks of visual stimulation, chewing, tongue tip sliding and repeated swallowing during fNIRS acquisition, to calculate the cortical activation β values covering a total of 41 channels in frontal, parietal and occipital lobes. ResultsDuring the preoral period, the bilateral pre-motor and supplementary motor cortex (PSMC), bilateral inferior prefrontal gyrus, right visual association cortex (AVC), and left primary motor cortex (PMC) were significantly activated (P < 0.05). During oral preparation, the right pars triangularis (PTG), right frontal polar area (FPA), right dorsolateral prefrontal cortex (DPC), left primary somatosensory cortex (PSC), left PSMC and left PMC were significantly activated (P < 0.05). During the transition between oral and pharyngeal phases, bilateral PSMC and bilateral PMC were significantly activated (P < 0.05). Bilateral PSC, bilateral PTG, bilateral FPA, bilateral orbitofrontal area, bilateral PSMC, bilateral DPC and bilateral PMC were significantly activated during two consecutive periods of oral and pharyngeal phases (P < 0.05). ConclusionThe swallowing movement requires the coordination of the frontal, parietal and occipital cortex. The main activated brain areas are different in different swallowing stages, and the PSMC and PMC are involved in most swallowing stages.

Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells

BACKGROUND@#Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. @*METHODS@#In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. @*RESULTS@#The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. @*CONCLUSION@#Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment.Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Afferent baroreflex failure with hyponatremia:A case report / 北京大学学报(医学版)

Afferent baroreflex failure(ABF)is a rare disease.It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medul-la.The recognized causes include trauma,surgery in related areas(radical neck tumor surgery,carotid endarterectomy),neck radiotherapy,brain stem stroke,tumor growth paraganglioma and hereditary diseases,among which the most common cause is extensive neck surgery or radiotherapy for neck cancer.The main manifestations are fluctuating hypertension,orthostatic hypotension,paroxysmal tachycardia and bradycardia.This case is a young man,whose main feature is blood pressure fluctuation,accom-panied by neurogenic orthostatic hypotension(nOH).After examination,the common causes of hyper-tension and nOH were ruled out.Combined with the previous neck radiotherapy and neck lymph node dissection,it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection,which was called ABF.At the same time,the patient was complicated with chronic hyponatremia.Com-bined with clinical and laboratory examination,the final consideration was caused by syndrome of in-appropriate antidiuretic hormone(SIADH).Baroreceptors controlled the secretion of heart rate,blood pres-sure and antidiuretic hormone through the mandatory"inhibition"signal.We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery,which leads to abnormal blood pres-sure regulation and nOH,while the function of inhibiting ADH secretion was weakened,resulting in higher ADH than normal level and mild hyponatremia.The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate,and to alleviate the on-set of symptomatic hypotension.At present,drug treatment is still controversial,and non-drug treatment may alleviate some patients'symptoms,but long-term effective treatment still needs further study.The incidence of ABF is not high,but it may lead to serious cardiovascular and cerebrovascular events,and the mechanism involved is extremely complicated,and there are few related studies.The reports of rele-vant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complica-tions.

Design and implementation of ultrasound therapy device for rabbit urethral scars / 国际生物医学工程杂志

Objective:To design a specialized ultrasound therapeutic device for rabbit urethral scars and to verify its applicability and effectiveness.Methods:New Zealand male rabbits were used as the experimental objects, and the ultrasound therapeutic instrument was customized according to the structure and size of the rabbit penises. The ultrasound therapeutic instrument included the ultrasound pulse emission and control system, the final-stage amplifier, and the ultrasound probe. Firstly, the ultrasound probe was designed according to the size and structure of rabbit penises, and the parameters of the ultrasound probe were determined by COMSOL finite element simulation and actual testing of the sound field distribution. Secondly, the driving circuit of the ultrasound probe was designed according to the parameters of the elements. Then the ultrasound pulse emission and control system based on the field-programmable gate array (FPGA) and the serial screen were designed. Subsequently, the ultrasound therapeutic instrument was subjected to a performance test and a safety test. The ultrasound therapeutic instrument was constructed to include the ultrasound amplifier and the ultrasound probe. Finally, a rabbit urethra reconstruction model was constructed, and eight white rabbits were randomly divided into a model group and an experimental group. The rabbits in the experimental group received the ultrasound therapeutic instrument for treatment of the urethra immediately, with an ultrasound frequency of 2 MHz, a pulse interval of 10 ms, and an output sound intensity of 0.73 W/cm 2. The treatment was performed twice a week (on Tuesday and Thursday), with 10 min of irradiation each time, lasting for four weeks. The rabbits in the model group did not receive any treatment. The area percentage of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tumor necrosis factor-α (TNF-α) staining-positive areas in rabbit urethral tissues were quantitatively analyzed, and the urethral circumference was calculated using Image J software. Results:Due to the addition of sound-absorbing materials, the sound pressure distribution in the treatment chamber was more uniform, and the average value of the standing wave ratio was 1.11, indicating that the structural design met the design requirements. In the overall performance test, the natural focal position of the three ultrasonic transducers was 10 mm, and the consistency of the sound field distribution meet the experimental requirements. The relationship between the peak sound pressure of each transducer and the power supply voltage was close to linear. The output sound intensity ranged from 0.35 to 0.74 W/cm 2, which met the experimental requirements. With the ultrasound output, the temperature of the test point increased slowly, and this experiment could increase the temperature of the tissue by up to 3.3 ℃, which would not lead to thermal damage to the tissue. Animal experiment results showed that the immunopositive area fraction of TGF-β1 in the urethral tissues of rabbits in the experimental group [(4.21 ± 1.32)%] was smaller than that of the model group [(8.53 ± 3.43)%] ( t = ?4.24, P < 0.001). The immunopositive area fraction of TNF-α in the urethral tissues of rabbits in the experimental group [(5.14 ± 2.72)%] was smaller than that of the model group [(7.23 ± 1.57)%] ( t = ?3.37, P < 0.05). The MMP-2 level in the urethral tissue of rabbits in the experimental group [(10.65 ± 2.24)%] was higher than that of the model group[(6.98 ± 2.74)%] ( t = 2.19, P < 0.05). The urethral circumference [(12 209 ± 2 743) μm] was higher than that of the model group [(10 127 ± 2 237) μm] ( t = 15.46, P < 0.05). Conclusions:An ultrasound therapeutic instrument dedicated to rabbit urethral scars has been successfully designed and can be used for the study of ultrasound treatment of rabbit urethral scars.

Analysis on Components Absorbed into Blood and Cerebrospinal Fluid of Schisandrae Chinensis Fructus Based on Sequential Metabolism / 中国实验方剂学杂志

ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus（SCF） based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism， intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration， and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC Q-Exactive Orbitrap MS） was used to analyze and compare the differences in the spectra of SCF extract， blank plasma， administered plasma， blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column（2.1 mm×100 mm， 1.7 µm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-7 min， 95%B； 7-12 min， 95%-35%B； 12-17 min， 35%-15%B； 17-20 min， 15%-12%B； 20-22 min， 12%-5%B； 22-23 min， 5%B； 23-25 min， 5%-95%B； 25-28 min， 95%B）. And heated electrospray ionization（HESI） was used with positive and negative ion modes， the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time， characteristic fragments， molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF， including lignans， flavonoids， amino acids， tannins， and others， of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation， methylation， demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats， it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.

Identification and expression analysis of the YABBY gene family in strawberry / 生物工程学报

YABBY proteins are important transcription factors that regulate morphogenesis and organ development in plants. In order to study the YABBY of strawberry, bioinformatic technique were used to identify the YABBY gene families in Fragaria vesca (diploid) and Fragaria×ananassa (octoploid), and then analyze the sequence characters, phylogeny and collinearity of the family members. The RNA-seq data and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique were used to assay the expression patterns of the family members. A green fluorescent protein (GFP) was fused with FvYABBYs and transiently expressed in tobacco leaf cells for the subcellular localization. As the results, six FvYABBY genes and 26 FxaYABBY genes were identified from F. vesca and F.×ananassa, respectively. The FvYABBY genes were grouped into five clades, and five family members were orthologous with AtYABBY genes of Arabidopsis. In F. vesca, all of the FvYABBYs were basically not expressed not expressed in root and receptacle, while FvYABBY1, FvYABBY2, FvYABBY5 and FvYABBY6 were highly expressed in leaf, shoot, flower and achene. In F.×ananassa, FxaYABBY1, FxaYABBY2, FxaYABBY5 and FxaYABBY6 were expressed in achene, and all FxaYABBY were poorly or not expressed in receptacle. Additionally, under the abiotic stresses of low temperature, high salt and drought, the expression of FvYABBY1, FvYABBY3, FvYABBY4 and FvYABBY6 were down-regulated, FvYABBY5 was up-regulated, and FvYABBY2 was up-regulated and then down-regulated. In tobacco leaf cells, the subcellular localization of FvYABBY proteins were in the nucleus. These results provides a foundation for the functional researches of YABBY gene in strawberry.

Analysis of Inhibitory Effect of Berberine Compounds on Acetylcholinesterase and Blood-brain Barrier Permeability / 中国实验方剂学杂志

ObjectiveTo examine the inhibitory effects of berberine compounds， including columbamine， on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier （BBB） permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration （IC50） of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters （Koff） of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds （including medicinal herbs and compound formulas） was conducted using ultra performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）. ResultBerberine compounds， including columbamine， exhibited strong inhibition of acetylcholinesterase， with IC50 values in the nanomolar range. Moreover， they displayed better drug-target binding kinetics characteristics （with smaller Koff values） than the positive control of donepezil hydrochloride （P<0.01）， indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer， as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance， this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease， providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.

AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial / 医学前沿

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

Research on the Construction Method and Application of Diagnosis and Treatment Knowledge Graph of Famous TCM Physicians Based on Medical Records / 世界科学技术-中医药现代化

Objective A knowledge graph construction pipeline of traditional Chinese medicine(TCM)diagnosis and treatment was designed and applied,aiming at the automatic construction of the"disease-symptom-pathogenesis-and medicine"knowledge graph based on the medical records of famous TCM physicians,to analyze,organize and present medical records efficiently.Methods Firstly,The entity extraction method of medical records combining Deep Learning and Regular Expression was designed to extract disease,symptom,pathogenesis,and TCM entities from unstructured medical records automatically;secondly,entity relationships were defined and the correlations between entities were calculated using HAN method,and then the"entity-relation-entity"triplets were built;the graph database Neo4j and Gephi were used for knowledge storage and visual display separately;Finally,the application was verified in the Medical records of lung cancer treated by the old famous TCM physicians.Results The precision,Recall and F1 of the knowledge extraction model for medical records entities extraction are 88.49%,90.02%and 89.25%,respectively,and each index is better than the comparison methods.A total of 1077 triples are extracted through entity correlation calculation,and the knowledge graph is successfully constructed.It can reflect the relationship between 'disease-symptom-pathogenesis-medicine' in the treatment of lung cancer by the famous specialists of TCM.Conclusion The method in this paper can effectively solve the extraction,organization and expression of clinical medical records of famous TCM physicians,and realize the automatic construction process from the text of medical records to the knowledge graph.Relevant research ideas and methods proposed in this paper could provide a reference for the construction of the diagnosis and treatment knowledge graph of famous TCM physicians based on medical records.

Expression and clinical significance of laboratory of genetics and physiology 2, retinoic acid inducible gene I and melanoma differentiation associated gene 5 in children with hand, foot and mouth disease / 中国小儿急救医学

Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.

Research progress of brain imaging in cognitive behavioral therapy for depression / 中华行为医学与脑科学杂志

The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.

Three⁃dimensional cephalometric measurement of craniofacial hard tissues with normal occlusion in Anhui area / 安徽医科大学学报

Objective@#To establish a three⁃dimensional cephalometric standardized value database for Anhui province , to study the craniofacial characteristics of normal adult population in Anhui , China and to provide effective information for making orthodontic and orthognathic surgery treatment plans of the craniofacial deformity.@*Methods@#160 normal occlusal volunteers were selected according to the inclusive and exclusive criteria and were photographed by Cone Beam CT (CBCT) . The coordinate system was established for the 3D model reconstructed with Dolphin based on CBCT data , and 38 hard tissue landmarks were located. 40 lines and 20 angles were defined and measured , and measurements were analyzed with SPSS 17. 0 , to evaluate craniofacial features of the overall , midface , maxilla , mandible , alveolar bone , and dentition of the standard population.@*Results@#The 3D cephalometric measurements of craniofacial hard tissues of normal adults in Anhui were obtained. The symmetry of craniofacial hard tissues was good both in males and females with the maximum asymmetry ratio of 2. 2% and the minimum of 0. 01% . The gender comparisons showed that most of lines measured of males were larger than those of females (P< 0. 01) , while there was no significant difference in the measurements of the midline deviation of upper and lower mandible , the relative deviation of the maxillary and mandible and the protrusion of upper and lower incisor. Additionally , there was no statistical significance in angles measured between genders , except for the occlusal plane angle. The results also showed that Chinese had unique facial features based on the measured data , compared with other ethnic populations.@*Conclusion@#The normal occlusal and maxillofacial hard tissue of Anhui Han has good symmetry. The gender obviously influences line measurements , with generally the measurements of males larger than females , but it has no effect on most angle measurements.

Molecular profile-based recommendations for postoperative adjuvant therapy in early endometrial cancer with high-intermediate or intermediate risk: a Chinese randomized phase III trial (PROBEAT) / 부인종양

Background@#The use of molecular categorisation is shifting paradigm towards the use of molecular information to refine risk stratification in endometrial cancer (EC). To date, evidence to support molecular-guided therapies is limited to retrospective studies and secondary molecular analyses of patients receiving standard treatment. The PROBEAT study is the first randomized phase III trial to evaluate tailored adjuvant treatment based on WHO-endorsed molecular classification in Chinese EC patients. It is expected to provide a clinical decision-making tool for adjuvant treatment of patients with high-intermediate risk (HIR) or intermediate risk (IR) EC to better optimise and personalise patient care and increase relapse-free survival. @*Methods@#The PROBEAT trial is a prospective, multicentre study led by Women’s Hospital of Zhejiang University Gynaecologic Oncology Group. Recruitment started on January 24, 2022, and 590 patients with HIR or IR endometrioid EC are expected to be recruited from 13 clinical centres in China. All tumor tissues will be classified into four molecular subtypes (POLEmut, MMRd, p53abn, or NSMP) based on WHO-endorsed molecular classification. Patients will be randomly assigned at a 2:1 ratio to either experimental arm and will receive molecular profile-based adjuvant treatment (observation in the POLEmut subgroup, vaginal brachytherapy in the MMRd or NSMP subgroup, or chemoradiotherapy in the p53abn subgroup) or to standard arm and will receive preferred adjuvant radiotherapy as recommended by the recent National Comprehensive Cancer Network guidelines version 1 (2022). The primary outcome is 3-year rates of recurrence. Secondary outcomes are relapse-free survival, overall survival, adverse events and health-related cancer-specific quality of life.

Preparation of 89Zr-labeled mesenchymal stem cells and PET monitoring in mice with systemic lupus erythematosus / 中华核医学与分子影像杂志

Objective:To label mesenchymal stem cells (MSCs) with 89Zr-oxine complex, and assess its characteristics of PET imaging in systemic lupus erythematosus (SLE) model (MRL/lpr mice). Methods:SLE mice were screened by 18F-FDG PET imaging. 89Zr-oxine was prepared and used for labeling MSCs (10 6 MSCs and 1 MBq 89Zr-oxine). 89Zr-oxine-labeled MSCs (0.2 MBq) were injected into MRL/lpr mice and BALB/c mice (each n=5) via tail vein at a dose of 1.2×10 6 cells per mouse, and followed with microPET imaging in vivo at 2 h, 6 h, 1 d, 3 d, 7 d, 10 d and 14 d after injection. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used to analyze the data. Results:MSCs was successfully labeled with 89Zr-oxine, with the labeling efficiency of 20% and cell viability >90%. MicroPET imaging showed that MSCs were mainly distributed in lungs and the liver sites at 2 h after injection. The number of MSCs homing to kidneys of MRL/lpr mice ( n=5) increased significantly 24 h after the injection, and the renal uptake of MSCs in MRL/lpr mice was much higher than that in BALB/c mice ((8.28±1.27) vs (4.33±0.94) %ID/g; t=3.54, P=0.024). The renal uptake increased firstly and then decreased and then leveled off, indicating MSCs homing to kidneys. Conclusions:A method for 89Zr-oxine labeling of MSCs is successfully established. 89Zr-labeled MSCs can home to kidneys of SLE mice. PET imaging of 89Zr-labeled MSCs can be effectively used to explore the in vivo distribution and migration behavior of transplanted MSCs during the treatment of diseases such as SLE.

Effect of normal iodized salt diet on urinary iodine concentration and iodine uptake rate in patients with differentiated thyroid cancer before 131I treatment / 中华核医学与分子影像杂志

Objective:To investigate the effects of normal iodized salt diet on urinary iodine concentration and iodine uptake rate in patients with differentiated thyroid cancer (DTC) before 131I treatment. Methods:A prospective study was conducted on patients with DTC (59 male patients and 130 female patients, age (43.7±12.2) years) who received 131I treatment for the first time after total thyroidectomy in the First Affiliated Hospital of Zhengzhou University between January 2021 and April 2022. Patients were divided into normal iodized salt diet group and limited iodized salt diet group according to whether iodized salt diet was administered 4 weeks before 131I treatment. The age, gender, urinary iodine concentration, iodine uptake rate and tumor risk stratification of the two groups were compared by independent-sample t test or χ2 test. In addition, according to the concentration of urinary iodine, patients were divided into group a1 (urinary iodine <200 μg/L) and group a2 (urinary iodine ≥200 μg/L). Logistic regression analysis was used to analyze the factors affecting urinary iodine concentration. Results:The urinary iodine concentration of normal iodized salt diet group was not significantly different from that of non-iodized salt diet group ((140.53±76.66) vs (121.74±74.64) μg/L; t=1.67, P=0.489). The iodine uptake rates at 2 h, 4 h and 24 h in the 2 groups were (3.77±1.06)% vs (3.42±0.97)%, (3.33±1.07)% vs (3.21±1.15)%, (2.90±2.60)% vs (3.23±2.94)%, respectively ( t values: 2.33, 0.68, -0.81, all P>0.05). There were no significant differences in age ( t=0.56, P=0.889), gender ( χ2=1.33, P=0.250) and tumor risk stratification ( χ2=0.14, P=0.709) between the two groups. Logistic regression analysis showed that tumor risk stratification was associated with urinary iodine concentration (odds ratio ( OR)=3.914, 95% CI: 1.505-10.176; P=0.005). Conclusion:Normal iodized salt diet may have no effect on urinary iodine concentration and iodine uptake rate of patients with DTC before 131I treatment.

Predictive value of metabolic tumor volume and total lesion glycolysis in 18F-FDG PET/CT imaging for prognosis in patients with extensive-stage small cell lung cancer / 中华核医学与分子影像杂志

Objective:To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with extensive-stage small cell lung cancer (ES-SCLC).Methods:From March 2019 to June 2020, 69 patients (55 males, 14 females, age: 38-87 years) with ES-SCLC who underwent pretreatment 18F-FDG PET/CT in First Affiliated Hospital of Zhengzhou University were retrospectively enrolled. The variables including gender, age, smoking, weight loss, liver metastasis, bone metastasis, malignant effusion, SUV max of the primary tumor, whole-body MTV (wbMTV) and whole-body TLG (wbTLG) (including wbMTV 40%, wbTLG 40%, wbMTV 2.5 and wbTLG 2.5) were analyzed. The predictors of overall survival (OS) were analyzed by using Kaplan-Meier method (log-rank test). Results:Of 69 ES-SCLC patients, 43(62%) died and 26(38%) were still alive by the end of follow-up, with a median survival time of 15.0(95% CI: 11.7-18.3) months. Univariate analysis revealed that age ( χ2=4.53, P=0.033), bone metastasis ( χ2=18.05, P<0.001), liver metastasis ( χ2=27.94, P<0.001), wbMTV 2.5 ( χ2=3.98, P=0.046), and wbTLG 2.5( χ2=5.80, P=0.016) were significant predictors of OS. Conclusion:wbMTV 2.5 and wbTLG 2.5 are assosciated with OS and may provide some reference value for predicting the prognosis of ES-SCLC patients.

Correlation analysis of BRAF V600E mutation with clinical pathological features and prognosis of differentiated thyroid cancer patients with different risk stratification / 中华核医学与分子影像杂志

Objective:To explore the relationship between B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation and clinical pathological features in patients with differentiated thyroid cancer (DTC), and to evaluate the value of BRAF V600E mutation in predicting the efficacy and follow-up of 131I treatment in DTC patients with different risk stratification. Methods:From January 2018 to June 2022, 893 DTC patients (205 males, 688 females, age (42.3±11.9) years) treated with 131I after total thyroidectomy in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Patients were divided into BRAF V600E mutation group ( n=729) and wild-type group ( n=164). According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into low-risk (39 cases), medium-risk (498 cases) and high-risk (356 cases), and the curative effect was divided into excellent response (ER) and non-excellent response (NER). The χ2 test, independent-sample t test and Mann-Whitney U test were used to compare differences between the two groups. Logistic regression analysis was performed to predict the influencing factors of treatment effect in DTC patients with different risk stratification. Results:The differences in age≥45 years, N stage, unilateral or bilateral DTC, multifocus, mode of operation, number and size of metastatic lymph nodes were statistically significant between BRAF V600E mutation group and wild-type group ( χ2 values: 4.45-17.40, t=-4.08, z=-3.08, all P<0.05). In medium- and high-risk stratification, the stimulated thyroglobulin (sTg) levels before and after 131I treatment were slightly higher in the BRAF V600E mutation group, while significantly sharp decreased of sTg and thyroglobulin antibody (TgAb) in wild-type group ( z value: from -9.30 to -2.65, all P<0.05). In medium- and high-risk stratification, 69.0%(60/87) and 64.3%(45/70) of BRAF V600E wild-type patients reached ER after 131I treatment, which were higher than those of mutant patients (57.4%(236/411) and 45.8%(131/286); χ2 values: 3.96, 7.39, P values: 0.046, 0.007). BRAF V600E mutation was the independent predictor affecting the efficacy of 131I treatment in DTC patients with medium- and high-risk stratification (odds ratio ( OR): 0.411 (95% CI: 0.196-0.864), 0.192 (95% CI: 0.096-0.384), P values: 0.019, <0.001). Conclusions:DTC patients with BRAF V600E mutation are related to the high invasiveness, and show poor improvement in biochemical indicators after initial 131I treatment. In addition, BRAF V600E mutation is an important factor in predicting the therapeutic effect of 131I in DTC patients with medium- and high-risk stratification.

Research progress of Mycobacterium abscessus complex diseases / 中华临床感染病杂志

Mycobacterium abscessus complex (MABC), a rapidly growing nontuberculous mycobacterium, has received increasing attention worldwide due to its rising isolation rate. The similarity of symptoms between MABC pulmonary disease and tuberculosis, different treatment methods required by different subtypes, as well as high levels of innate, adaptive and acquired antibiotic resistance, make MABC treatment more difficult and lead to unfavorable clinical outcomes of patients. This article reviews the basic characteristics, common antibiotic resistance mechanisms, as well as diagnosis and treatment of MABC, to provide reference for future research and clinical treatment of MABC lung disease.