Objective:To explore the effect of TP53 mutation variant allele frequency(VAF)on the prognosis of diffuse large B-cell lymphoma(DLBCL)patients.Methods:This study included 155 patients with DLBCL who were first diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2009 to March 2022. Complete clinical data and paraffin-embedded tumor tissue samples were obtained,and DNA was extracted from tumor tissues.The gene mutation profile of DLBCL patients was detected and analyzed by second-generation sequencing technology.Kaplan-Meier method was used to analyze the mutation status of TP53 gene and the relationship between mutation VAF and OS.Cox regression univariate and multivariate analysis was use to analyze the independent factors affecting OS.A nornogram model for predicting 1,3,and 5 years OS in DLBCL patients were established to evaluated the performance of the model based on C-index and calibration curves.Results:The average value of TP53 mutation VAF in male DLBCL patients was significantly higher than that in female patients (P<0.05 ).Patients with TP53 mutantion had shorter OS than those with wild-type patients (P=0.030).The optimal VAF threshold for TP53 mutation based on OS stratification was 33.61％(P<0.001),and patients with TP53 mutation VAF≥34％had shorter OS than those with TP53 mutation VAF<34％and wild-type patients (P<0.001).Multivariate Cox analysis showed that TP53 mutation VAF≥34％ was an independent poor predictor of OS (HR=4.05,P<0.001),and IPI score ≥3 was an independent predictor of OS poor (HR=2.27,P=0.008).In combination with factors with independent prognostic significance obtained from multi-factor analysis,we constructed a nomogram model for predicting 1-year,3-year,5-year OS in DLBCL patients.The results showed that the C index of TP53-mutated VAF combined with IPI model was 0.743,which predicted the value of 1-year,3-year,and 5-year OS in DLBCL patients.Calibration curves show that the model has good agreement between predicted and actual survival of DLBCL patients at 1-year,3-year,and 5-year. Conclusion:TP53 mutant VAF has prognostic value in DLBCL patients,and TP53 mutant VAF≥34％ is an independent risk factor for OS in DLBCL patients.The prognosis model of TP53 mutation VAF combined with IPI nomogram constructed in this study has good predictive performance for DLBCL patients.

Objective:To investigate the potential value of saccade and antisaccade parameters in early identification of Parkinson′s disease (PD) and its motor subtypes.Methods:A total of 111 PD patients [tremor dominant (TD) type in 45, postural instability/gait difficulty (PIGD) type in 54 and indeterminate type in 12)] and 54 healthy controls were recruited from Department of Neurology, Guangdong Provincial People′s Hospital from July 2022 to July 2023. All subjects underwent oculomotor test including visually guided saccades and volitional antisaccades by the Eyeknow-M10-B Eye tracker. For PD patients, TD and PIGD scores were measured using the Movement Disorder Society Unified Parkinson′s Disease Rating Scale (MDS-UPDRS) Part Ⅱ and Part Ⅲ. Oculomotor parameters among TD, PIGD patients and healthy controls were firstly compared. Multiple linear regression analyses were performed to assess the relationship between ocular parameters with differences and TD/PIGD score. Then receiver operating characteristic (ROC) curve analysis was made between PD patients and healthy controls, as well as between PIGD and TD subtypes.Results:Compared to healthy controls, PD patients showed significantly decreased saccadic accuracy [100.0%(90.0%, 100.0%) vs 100.0%(100.0%, 100.0%), U=1 732.500, P<0.001], prolonged latency [252.2(228.5, 300.1) ms vs 227.7(214.2, 241.8) ms, U=1 401.000, P<0.001], minimum duration [233.6(211.2, 278.8) ms vs 211.0(200.0, 222.5) ms, U=1 534.500, P<0.001], average duration [356.6(313.8, 427.8) ms vs 279.4(267.4, 312.9) ms, U=881.000, P<0.001],as well as decreased peak [444.4(335.0, 593.7) °/s vs 526.7(412.6, 696.2) °/s, U=1 971.000, P=0.007] and average velocity [196.3(144.4, 240.5) °/s vs 256.7(226.7, 312.0) °/s, U=1 330.000, P<0.001] in saccades. And in antisaccades, PD patients also showed prolonged latency [432.0(362.9, 599.8) ms vs 352.9(309.8, 407.6) ms, U=1 553.000, P<0.001], minimum duration [333.4(299.8, 377.6) ms vs 290.1(263.9, 332.9) ms, U=1 608.000, P<0.001], average duration [518.2(462.7, 603.5) ms vs 424.2(377.1, 473.5) ms, U=1 181.000, P<0.001], decreased peak [458.5(327.9, 604.3) °/s vs 560.4(440.3, 698.5) °/s, U=1 838.500, P=0.001] and average velocity [186.6(143.1, 228.1) °/s vs 263.2(217.2, 301.5) °/s, U=1 131.000, P<0.001]. There was no statistically significant difference in antisaccadic accuracy [55.0%(15.0%, 80.0%) vs 66.7%(39.4%, 86.9%), U=2 167.500, P=0.053]. Compared with TD subtype, PIGD patients showed significantly decreased antisaccadic peak velocity [416.2(300.3, 534.3) °/s vs 527.1(402.3, 636.4) °/s, U=-26.474, P=0.009]. After adjusting for age, gender and education, antisaccadic peak velocity was negatively correlated with PIGD score in PD patients (β=-0.296, P=0.001), and no correlation with TD score was found. The ROC analysis was performed on combined saccadic and antisaccade metrics between PD patients and healthy controls, with area under the curve (AUC) as 0.918. For antisaccadic peak velocity between PIGD and TD subtypes, the AUC was 0.690. Conclusions:Eye movement metrics have potential value in distinguishing PD patients from healthy controls. The antisaccadic peak velocity is related to the severity of motor symptoms in PIGD patients, which is helpful for distinguishing the motor subtypes of PD patients.

The theoretical foundations of the forward and inverse problems of two conductivity imaging methods based on magneto-acoustic coupling effects,including magneto-acoustic tomography(MAT)and magneto-acousto-electrical tomogra-phy(MAET),were introduced.The research progress of the conductivity reconstruction methods with different imaging strate-gies was reviewed.The problems of the conductivity reconstruction methods based on magnetoacoustic coupling effects were analyzed in terms of acoustic source model construction,reconstruction algorithm and imaging speed,and the future develop-ment directions were pointed out.[Chinese Medical Equipment Journal,2024,45(7):94-104]

Objective To explore the clinical rational use evaluation method for high-value medical consumables in diagnosis related groups(DRG)using association rules in order to provide references for the supervision of clinical rational use of high-value medical consumables.Methods The cardiovascular department was taken as an example.Firstly,K-means algorithm was applied to cluster analysis of DRG cases in the department,and representative cases were selected as the research objects;secondly,Apriori algorithm was used to mine the frequent item sets of DRG patient groups,the high-value medical consumables in the department and the rules of association between DRG patient groups and medical consumables;finally,two indicators of the importance of regulation and rationality of the use of medical consumables were designed to evaluate the importance of regulation and rationality of the use of high-value medical consumables.Results There were two common DRG patient groups in the cardiovascular department,including FM39 percutaneous cardiac catheterization and FM19 percutaneous coronary stent implantation,and the frequently used medical consumables contained vascular sheath,contrast catheter,pressure monitoring kit,triple three-way stopcock and coronary guide wire in the two groups.The common combinations of medical consumables used in the FM39 DRG patient group comprised of vascular sheath,contrast catheter,pressure monitoring kit,triple three-way stopcock and coronary guide wire,which were close to that of the cardiovascular department;there were some additional consumables involved in the common combinations in the FM19 group such as occluder,coronary guide catheter,pressure pump,drug-eluting stent and coronary dilation balloon.The top three medical consumables in terms of regulatory importance were cutting balloon,coronary guide wire and drug-eluting stent;using the confidence level from January to September 2022 as a reference,from January to September 2023 the rationality of using high-value consumables in FM39 group went higher by 5.08％while that in FM19 group went lower by 9.23％.Conclusion The association rule-based evaluation method for the use of medical consumables in DRG patient groups can be used for assessing the importance of regulation and rationality of the use of high-value medical consumables,which provides references for the supervision of clinical rational use of high-value medical consumables.[Chinese Medical Equipment Journal,2024,45(11):67-71]

Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the feasibility of using quantitative parameters of double contrast-enhanced ultrasound (DCUS) to noninvasively predict lymphatic metastasis in gastric cancer before operation.Methods:From December 2021 to October 2023, 119 patients undergoing gastrectomy at the Second Hospital & Clinical Medical School, Lanzhou University, were enrolled retrospectively. Based on the pathological findings, they were divided into lymph node metastasis (N1, 94 cases) and non-lymph node metastasis (N0, 25 cases) groups. All patients underwent DCUS within 3 days before surgery. Previous to DCUS, lesions′ location and ultrasonic T-staging were recorded by conventional ultrasound. Quantitative parameters such as arrival time (AT), time to peak (TTP), baseline intensity (BI), peak intensity (PI) and wash-in slope (WIS) were obtained by the time-intensity curve (TIC) automatically, and then manually calculated enhanced intensity (ΔPI=PI–BI) and enhanced time (ΔTTP=TTP–AT). Binary Logistic regression analysis was used to screen independent risk factors for predicting lymph nodes metastasis in gastric cancer, and regression models were established.Results:Statistical tests revealed significant differences in ultrasonic T-staging ( P<0.001) and degree of differentiation ( P=0.015) between N1 and N0 group. Among DCUS quantitative parameters, statistical differences in PI, ΔPI and WIS were observed between the two groups (all P<0.05), while no significant differences were found in BI, AT, TTP and ΔTTP (all P>0.05). Logistic regression analysis showed that ultrasonic T-staging and WIS were independent risk factors for predicting lymphatic metastasis. The regression model built on the above two factors performed well in predicting lymph nodes metastasis, with an area under the curve of 0.905, accuracy of 93.3% (superior to the prediction model based on DCUS quantitative parameters alone, P<0.05), sensitivity of 95.7% and specificity of 84.0%. Conclusions:DCUS quantitative parameters may be helpful to evaluate lymphatic metastasis of gastric cancer prior to surgery, and the accuracy of prediction would be improved by combing with ultrasonic T-staging.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors