Objective:To explore the efficacy and safety of bortezomib or thalidomide combined with recombinant human erythropoietin(rhEPO)in the treatment of multiple myeloma(MM).Methods:A total of 80 patients with MM who were treated in the Second People's Hospital ofWuhu from January 2013 to December 2018 were selected as the research subjects,and they were divided into bortezomib group(n=40)and thalidomide group(n=40)by the simple randomization method.The bortezomib group received bortezomib regimen combined with rhEPO therapy,and the thalidomide group was given thalidomide regimen combined with rhEPO therapy,and all patients were treated for 3 courses with every 3 weeks as a course of treatment.The clinical efficacy after 3 courses of treatment,and tumor-related biochemical indicators[lactate dehydrogenase(LDH),β 2-microglobulin([3 2-MG),vascular endothelial growth factor(VEGF),apoptosis inhibitory protein Survivin],bone marrow-related indicators[serum M-protein,bone marrow plasma cells,hemoglobin(Hb)]and coagulation function indicators[activated partial thromboplastin time(APTT),prothrombin time(PT),plasminogen activator inhibitor(PAI),total circulating microparticles(TMPs)]before treatment and after 3 courses of treatment were compared between the two groups of patients.The occurrence of adverse reactions during the treatment in the two groups of patients was recorded.Results:After 3 courses of treatment,the ORR rate of 92.5％in bortezomib group was higher than 90.0％in thalidomide group,but the difference was not statistically significant(P＞0.05).The levels of LDH,[3 2-MG,VEGF,Survivin,serum M-protein,bone marrow plasma cells,APTT,PT,PAI and TMPs in the two groups after 3 courses of treatment were significantly lower or shorter than those before treatment,and the above indicators in bortezomib group were significantly lower or shorter than those in thalidomide group(P＜0.05).After 3 courses of treatment,the expression level of Hb in the two groups was significantly higher than that before treatment,and the Hb level in bortezomib group was significantly higher than that in thalidomide group(P＜0.05).During the treatment process,the incidence rates of adverse reactions in bortezomib group were significantly lower than those in thalidomide group(P＜0.05).Conclusion:Thalidomide regimen or bortezomib regimen combined with rhEPO has similar clinical efficacy on MM,but bortezomib regimen combined with rhEPO is more prominent and safer on improving tumor-related biochemical indicators,bone marrow-related indicators and coagulation status in patients with MM.

Objective To carry out rigid-body inverse dynamics modelling and analysis of a self-designed 6RSS parallel bio-inspired masticatory robot.Methods Firstly,the functions of kinematic variables including translational/rotational velocities and accelerations were derived for rigid-body inverse dynamics modelling.Secondly,the rigid-body inverse dynamics model was established with the Newton-Euler's law.Finally,the chewing motion trajectories of the oral health volunteers were tracked and numerical calculations were carried out in the case where the robot was subjected to a chewing reaction force.Results Numerical calculations showed that the driving torque and the constraint force of the robot peaked when the chewing reaction force was at its maximum.Conclusion The external force has a large impact on the inverse dynamics of the robot,and theoretical references are provided for the motion control and optimal design of the robot.[Chinese Medical Equipment Journal,2024,45(3):16-22]

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective: To investigate the effect of 1-acyl-sn-glycerol-3-phosphate acyltransferaseδ (APGAT4) on the growth and lenvatinib resistance of hepatocellular carcinoma (HCC), and provide novel targets for HCC treatment. Methods: Using the bioinformatics methods to screen out upregulated genes in lenvatinib resistant cell lines from GEO dataset and survival related genes from TCGA dataset. Immumohistochemical staining was used to detect the expression AGPAT4 in HCC tissues, and its correlation with patients' survival. CCK8, EdU, cell cycle, and cell apoptosis assays were used to investigate the impact of role AGPAT4 on the proliferation and lenvatinib reistance of HCC cells. AGPAT4 stable knockdown cell line and subcutaneous nude mouse model were established to test the therapeutic effects of Lenvatinib. Analysis of variance was used to compare the differences between data sets. Results: APGAT4 was the common factor that predicted poor survival and Lenvatinib resistance. The mRNA and protein levels of APGAT4 were significantly upregulated in HCC tissues compared to the para-tumor tissues (P < 0.05). Using siRNA could significantly knocked down the mRNA and protein expression of APGAT4 in HCC cell lines Hep3B and HCCLM3. Compared with the control group, the proliferation ability of HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group was significantly inhibited, and the cell cycle was arrested in G2/M phase (P < 0.05). In addition, compared to the control group, HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group showed significant decrease in the Lenvatinib half maximal inhibitory concentration, and were more sensitive to lenvatinib-induced apoptosis (P < 0.05). In HCC subcutaneous nude mouse model, compared to the control group, the growth of tumor in APGAT4 knockdown group was significantly suppressed, and more apoptosis cells were induced (P < 0.05). Conclusion: APGAT4 promotes the growth and Lenvatinib resistance of HCC, which is a potential target for HCC treatment. Targeting APGAT4 treatment is conducive to inhibit the growth and Lenvatinib resistance of HCC.
Animals ; Mice ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Mice, Nude ; Cell Line, Tumor ; Cell Proliferation ; RNA, Messenger ; Gene Expression Regulation, Neoplastic

Bradyarrhythmias are commonly encountered in clinical practice. While there are several electrocardiographic criteria and algorithms for tachyarrhythmias, there is no algorithm for bradyarrhythmias to the best of our knowledge. In this article, we propose a diagnostic algorithm that uses simple concepts: (1) the presence or absence of P waves, (2) the relationship between the number of P waves and QRS complexes, and (3) the regularity of time intervals (PP, PR and RR intervals). We believe this straightforward, stepwise method provides a structured and thorough approach to the wide differential diagnosis of bradyarrhythmias, and in doing so, reduces misdiagnosis and mismanagement.
Humans ; Bradycardia/therapy* ; Algorithms ; Diagnosis, Differential ; Electrocardiography

OBJECTIVE: To investigate the relationship between the shape of the lateral wall and the early failure of internal fixation in the fracture of the femoral trochanteric region(FFT). METHODS: Total 295 patients with femoral trochanteric fracture underwent internal fixation from January 2015 to January 2020 were selected. The patients were divided into two groups according to whether there was early internal fixation failure after surgery, 19 patients in the failure group and 276 patients in the normal group. Gender, affected side, age, AO classification, body mass index(BMI), preoperative hemoglobin, X-ray measurement of lower lateral wall thickness, preoperative internal diseases, intraoperative blood loss, postoperative tip apex distance(TAD), postoperative neck shaft angle, operation time and other data were compared between two groups. The shape of the lateral wall was compared between two groups, and the correlation between the shape of the lateral wall and the early internal fixation failure of femoral trochanteric fracture was analyzed. RESULTS: All patients were followed up for more than 1 year. There was no significant difference between two groups in terms of intraoperative blood loss, operation time, postoperative TAD, and postoperative neck shaft angle(P>0.05). At the latest follow-up, the visual anaglue scale (VAS) of the failure group was higher than that of the normal group(P<0.01), and the Harris score of the failure group was lower than that of normal group(P<0.05). The receiver operator characteristic (ROC) curve between shape of lateral wall and failure of early internal fixation of femoral trochanteric fracture was drawn. The critical value of the midpoint lateral wall thickness was 16.5 mm, and the area under the ROC curve was 0.845;The critical value of average sidewall thickness was 16.5 mm, and the area under ROC curve was 0.838;The critical value of the axial area of the sidewall was 7.5 mm, and the area under the ROC curve was 0.826. CONCLUSION The shape of the lateral femoral wall measured by CT could be used as a predictive factor for the early failure of internal fixation of femoral trochanteric fractures. For patients at risk, more reasonable surgical plans and postoperative preventive measures should be developed.
Humans ; Treatment Outcome ; Fracture Fixation, Intramedullary ; Bone Nails ; Retrospective Studies ; Hip Fractures/surgery* ; Fracture Fixation, Internal

OBJECTIVES: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. METHODS: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA₀ group (received one session of EA), EA_6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA_48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA_6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). RESULTS: The amplitude of MEPs at T1 and T2 in the EA₀ group, at T0* in the EA_6h group and at T1, T2 and T3 in the EA_48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA₀ group and the EA_48h group was higher than that in the EA_6h group (P<0.001, P<0.01); at T2, it was higher in the EA₀ group when compared with that in the EA_6h group (P<0.01); at T3, the amplitude in the EA₀ group and the EA_6h group was lower than that of the EA_48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA₀ group and the EA_48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA_6h group (P<0.05); at T2, it was reduced in the EA_48h group when compared with that of the EA_6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). CONCLUSIONS Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.
Humans ; Electroacupuncture ; Motor Cortex/physiology* ; Transcranial Magnetic Stimulation/methods* ; Upper Extremity ; Exercise ; Muscle, Skeletal/physiology*

Objective: To investigate the predictive value of blood cell parameters in children with vasovagal syncope (VVS). Methods: In this case-control study, the VVS group included 111 patients with unexplained syncope or prodromata who were diagnosed with VVS by head-up tilt test in the Second Xiangya Hospital, Central South University from January 2018 to October 2020, and 111 healthy children were enrolled as control. The differences in blood cell parameters between the 2 groups were compared by t test and Mann-Whitney U test. Multivariate binary Logistic regression was used to analyze the independent correlation factors of VVS, and receiver operating characteristic (ROC) curve to explore the predictive value of blood cell parameters for diagnosing VVS. Results: Sex composition ratios were consistent in the 2 groups (51 males vs. 60 females), while the age of the VVS group was higher than that of the control group (11.0 (8.0, 12.5) vs. 8.0 (7.0, 11.0) years, Z=4.39, P<0.001). Compared with the control group, VVS group had lower level of white blood cell (WBC) (6.0 (5.3, 7.1)×10⁹ vs. 8.6 (6.7, 10.1)×10⁹/L, Z=-7.96, P<0.001), lymphocyte (LY) (2.3 (1.9, 2.7)×10⁹ vs. 4.0 (2.8, 6.3)×10⁹/L, Z=-8.49, P<0.001), lymphocyte ratio (0.39 (0.33, 0.44) vs. 0.52 (0.37, 0.69), Z=-5.59, P<0.001), monocyte (0.3 (0.3, 0.4)×10⁹ vs. 0.4 (0.3, 0.6)×10⁹/L, Z=-6.19, P<0.001), eosinophil (0.1 (0.1, 0.2)×10⁹ vs. 0.2 (0.2, 0.4)×10⁹/L, Z=-5.75, P<0.001), mean corpuscular-hemoglobin concentration (MCHC) ((328±12) vs. (333±11) g/L, t=-3.27, P<0.001) and blood platelet (263 (235, 313)×10⁹ vs. 341 (295, 409)×10⁹/L, Z=-2.69, P<0.001), but higher neutrophil ratio (0.53 (0.48, 0.58) vs. 0.37 (0.22, 0.54), Z=5.86, P<0.001), hematocrit (0.39±0.04 vs. 0.37±0.04, t=2.75, P=0.006), mean corpuscular volume (MCV) (85 (82, 88) vs. 81 (78, 84) fl, Z=5.56, P<0.001), mean corpuscular hemoglobin (28 (27, 29) vs. 27 (26, 28) pg, Z=3.39, P=0.001), red cell distribution width (39 (37, 41) vs. 37 (36, 40) fl, Z=4.02, P<0.001) and mean platelet volume (11 (10, 11) vs. 10 (9, 11) fl, Z=2.81, P=0.005) levels. After adjusting for confounding factors such as sex and age, LY (OR=0.42, 95%CI 0.29-0.62, P<0.001), WBC (OR=0.75, 95%CI 0.59-0.95, P=0.015), MCHC (OR=0.94, 95%CI 0.91-0.97, P<0.001) were independent negative correlation factors of VVS, while MCV (OR=1.08, 95%CI 1.01-1.15, P=0.021) was independent positive correlation factor. ROC curve showed that the combination of LY, WBC, MCV and MCHC had acceptable predictive value for the diagnosis of VVS, with area under curve of 0.88, sensitivity of 0.80, specificity of 0.83, and Youden index of 0.63. Conclusions: Compared with healthy children, the blood cell parameters usually change in those with VVS. Combination of LY, WBC, MCHC and MCV can facilitate the diagnosis of VVS in children with unexplained syncope or prodromata.
Case-Control Studies ; Child ; Female ; Humans ; Lymphocytes ; Male ; Syncope ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

Objective:To explore the material basis and mechanism of Sangjiang Ganmao injection （SG） in the treatment of common cold by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） and network pharmacology. Method:UPLC-Q-Orbitrap HRMS was used to identify the chemical components of SG with mobile phase of acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-10 min， 4%-15%A； 10-35 min， 15%-30%A； 35-45 min， 30%-33%A； 45-55 min， 33%-60%A； 55-58 min， 60%A）， flow rate of 0.2 mL·min^-1， electrospray ionization （ESI） and scanning range of m/z 100-1 500 under positive and negative ion modes. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and GeneCards 5.0 database were used to screen and predict the potential targets of chemical components in SG， STRING 11.0 database and Cytoscape 3.7.2 software were used to construct protein-protein interaction （PPI） network model， gene ontology （GO） analysis and pathway analysis were performed on potential targets by Metascape 3.5， Reactome database and Kyoto Encyclopedia of Genes and Genomes （KEGG）， Cytoscape 3.7.2 software was used to build the network of "herbs-ingredients-key targets". Result:A total of 54 components in SG were identified， and 80 potential targets of SG for treatment of common cold were predicted and screened based on this. SG exerted therapeutic effects by acting on targets such as interleukin （IL）-6， tumor necrosis factor （TNF） and IL-10， and signaling pathways such as IL-17 signaling pathway， TNF signaling pathway and interaction of cytokine receptors. Conclusion:SG may interfere with the expression of inflammatory cytokines by acting on related targets and pathways such as inflammation and immune system， and regulate the immune function of the body as a whole， thereby exerting a therapeutic effect.

Fourteen compounds were isolated from the ethanol extract of Dalbergiae Odoriferae Lignum by various chromatographic techniques, including column chromatographies on silica gel, Sephadex LH-20 and semi-preparative HPLC. Their structures were determined by spectroscopic techniques as S-3'-hydroxy-7,2',4'-trimethoxyisoxane(1), 2-(2',4'-dimethoxyphenyl)-6-hydroxybenzofuran(2), 2-(2'-hydroxy-4'-methoxyphenyl)-6-methoxybenzofuran(3), 7,2',4'-trimethoxydihydroisoflavone(4), sativanone(5), 3,9-dimethoxy-6H-benzofuro[3,2-c]chromen-6-one(6),(6 aS,11 aS)-homopterocarpin(7),(6 aS,11 aS)-8-hydroxy-3,9-dimethoxypterocarpan(8),(6 aS,11 aS)-3,8,9-trimethoxypterocarpan(9), isodalbergin(10), isoliquiritigenin(11), butein(12), butin(13) and 3,7,4'-trihydroxyflavone(14). Among them, compound 1 was a new compound, while 2 and 3 were new natural products, 6, 8, 9 and 14 were isolated for the first time from Dalbergiae Odoriferae Lignum. Compounds 1-14 were tested for their cytotoxic activity against human hepatoma cell line BEL-7402, human gastric cancer cell line SCG-7901, human lung cancer cell line A549, human chronic myeloid leukemia cell line K562 and HeLa human cervical cancer cellline by MTT method. Compound 1 exhibited significant cytotoxicity with IC_(50) values ranging from 2.85 to 11.62 μg·mL~(-1). In addition, 2, 11 and 12 showed weak cytotoxic activities.
Antineoplastic Agents ; Chromatography, High Pressure Liquid ; HeLa Cells ; Humans