ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Purpose/Significance To analyze the technical situation of patent owners in the field of clinical decision support system(CDSS)in China as a whole,so as to provide references for CDSS related technical research.Method/Process Firstly,the CDSS patent data are analyzed from the aspects of application trend,patent disclosure,technology field distribution,etc.,then the patentees are di-vided into different categories,and their technical concerns are analyzed by word frequency and interword vector.Finally,the technology correlation and patent exclusives are analyzed based on the active patentees.Result/Conclusion The number of CDSS patent disclosure shows an overall increasing trend.This field has not formed a technological monopoly in China.Government departments and research in-stitutions should pay attention to the possible financial risks.

Objective:To investigate the safety and efficacy of posterior apical total intervertebral release (IVR) combined with posterior column osteotomy (PCO) in the treatment of rigid scoliosis.Methods:This study retrospectively analyzed the clinical and radiographic data of 27 patients with rigid scoliosis who underwent posterior total IVR combined with PCO in the apical region from July 2017 to September 2023. There were 10 males and 17 females with an age of 19.3±8.8 years (range 11-48 years). Among them, there were 16 cases of idiopathic scoliosis, 7 cases of neuromuscular scoliosis, 1 case of congenital scoliosis, 1 case of Marfan syndrome with scoliosis, 1 case of neurofibromatosis with scoliosis, and 1 case of osteogenesis imperfecta with scoliosis. The mean Cobb angle of the main curve was 75.4°±13.7° (range 58.7°-110.2°) preoperatively. The mean flexibility of the main curvature is 15.7%±4.7% (range 2.5%-24.3%). Preoperative computer tomography showed that the area of the IVR channel in the convex and concave side of the apical region was 128.1±23.3 mm 2 and 89.5±18.6 mm 2, respectively. The area of the convex IVR was significantly higher than that of the concave IVR. Results:All 27 patients underwent surgery successfully. Total IVR was performed at an average of 3.4±0.7 levels in the apical region. SPO and Ponte osteotomy were performed at 2.7±0.7 and 4.9±1.1 levels, respectively. The mean fusion segment is 11.2±2.0. The operation time, estimated blood loss, and follow-up time were 7.5±0.9 hours (range 6.0-9.8 hours), 1 103.7±845.1 ml (range 300-4 500 ml), and 20.0±14.2 months (range 5-56 months), respectively. The preoperative, postoperative, and final follow-up's mean coronal Cobb angles of the main curve were 75.4°±13.7°, 18.2°±6.5° and 18.6°±6.5°, respectively. The mean correction rate was 75.7%±5.3%. In cases of thoracolumbar kyphosis, the preoperative, postoperative, and final follow-up mean sagittal Cobb angles were 47.2°±4.7°, 22.8°±9.1° and 23.8°±8.9°, respectively. The mean correction rate was 49.5%±18.9%. The mean axial vertebral rotation (AVR) in the IVR region was 24.6°±7.6° preoperatively and was corrected to 11.6°±5.6° postoperatively. The mean correction rate for AVR was 54.0%±11.3%. The coronal, sagittal Cobb angles and AVR postoperatively were significantly lower than those preoperatively ( P<0.001). This case series reported 4 cases of postoperative pleural effusion and 1 case of pulmonary infection, and all of them were cured through conservative treatment. One patient developed incision infection 2 months postoperatively and recovered through debridement surgery. Two patients had proximal junctional kyphosis, one of them underwent revision surgery, and another case was treated with braces. Conclusion:Posterior multi-segment total IVR combined with PCO is a safe and effective surgical procedure for the treatment of rigid scoliosis. The procedure of total IVR was recommended as a supplement for better release of the rigid spine when traditional release methods are not effective.

Objective:To investigate the short-term and medium-term changes of the left ventricular ejection fraction (LVEF) and the predictive value of relevant electrocardiogram (ECG) indexes in children with dilated cardiomyopathy (DCM) complicated with complete left bundle branch block (CLBBB).Methods:Children clinically diagnosed with DCM in the Department of Heart Center, Women and Children′s Hospital, Qingdao University and Beijing Anzhen Hospital, Capital Medical University between November 2011 and August 2020 were retrospectively recruited.According to the combination of CLBBB, they were divided into CLBBB group and non-CLBBB group.Echocardiogram and ECG were regularly performed.Short-term and medium-term changes of LVEF based on the 1-5-year follow-up data were compared between groups.COX proportional hazards model and Kaplan-Meier multiplicative limit method were used to analyze the predictive value of ECG indexes of LVEF changes in children with DCM combined with CLBBB.Results:Ninety-four children with DCM were enrolled, including 35 cases in CLBBB group and 59 cases in non-CLBBB group.There was no difference in baseline LVEF between groups.However, significant differences were found in QRS duration, corre-cted QT interval(QTc), R peak time in lead V 5 (T V5R) and QRS notching or slurring between groups ( P<0.05). LVEF of all children showed an upward trend within one year after onset, while the Z value of eft ventricular end diastolic diameter(LVEDd) showed a downward trend, and the two indexes tended to be stable within 1 - 5 years.The Z value of LVEDd in CLBBB group was significantly higher than that of non-CLBBB group, while LVEF was significantly lower (all P<0.05). The mean LVEF of CLBBB group slightly fluctuated around 50%, that of LVEF in non-CLBBB group was 60%.The multivariate COX regression analysis showed that QRS duration ( HR=0.979; 95% CI: 0.960-0.999, P<0.05) and QTc ( HR=0.988; 95% CI: 0.979-0.998, P<0.05) were independent predictors of LVEF recovery in children with DCM.Kaplan-Meier method showed a significant difference of LVEF normalization between DCM children with different QRS durations ( P<0.05), which was also detected in those with QTc interval ( P<0.05). Conclusions:LVEF of children with DCM combined with CLBBB increases in the short term after standard treatment, and then being stable.CLBBB can affect the recovery of left ventricular systolic function in children with DCM.Moreover, QRS duration and QTc interval are independent predictors of LVEF recovery in DCM children.

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

Objective:To evaluate the short-term influence of bilateral subthalamic deep brain stimulation (STN-DBS) in anxiety symptoms and quality of life in patients with Parkinson's disease (PD).Methods:Thirty-nine PD patients underwent bilateral STN-DBS in our hospital from August 2017 to August 2018 were chosen in our study. Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scales were performed in these patients before and one month after surgery, and at the last follow-up, respectively. Parkinson's Disease Questionnaire-8 (PDQ-8) was performed before surgery and at the last follow-up. Statistical methods were used to analyze the differences of the above scores at different time points, and correlations between each two improvement degrees of above scores. The participants were subsequently divided into four groups based on preoperative BAI scores: no anxiety group ( n=18), mild anxiety group ( n=10), moderate anxiety group ( n=8), and severe anxiety group ( n=3); the above scales were performed. Results:(1) The BAI scores of 39 patients one month after surgery and at the last follow-up (14 [8, 20] and 9 [3, 14]) were significantly lower than those before surgery (16 [9, 27]), and the BDI scores (8[6, 16]) and PDQ-8 scores (3 [2, 6]) at the last follow-up were significantly lower than those before surgery (15 [8, 21] and 9 [6, 13], P<0.05). (2) Correlation analysis revealed that the improvement degree of BAI scores was positively correlated with that of BDI scores ( r s=0.722, P=0.000), and negatively correlated with preoperative baseline scores of BDI and PDQ-8, respectively ( r s=-0.714, P=0.000; r s=-0.378, P=0.018). (3) The BAI scores in the mild and moderate anxiety groups at the last follow-up were significantly lower as compared with the preoperative baseline BAI scores ( P<0.05). The improvement degree of BAI scores in mild, moderate, and severe anxiety groups was significantly higher than that in the no anxiety group ( P<0.05). Conclusion:The bilateral STN-DBS has considerable benefit effect on anxiety symptoms and health-related quality of life in PD patients during short-term follow-up, suggesting an involvement of STN in the pathogenesis of anxiety in PD.

Brucella is an intracellular pathogen that invades a host and settles in its immune cells; however, the mechanism of its intracellular survival is unclear. Modification of small ubiquitin-related modifier (SUMO) occurs in many cellular activities. E2 conjugating enzyme 9 (Ubc9) is the only reported ubiquitin-conjugating enzyme that links the SUMO molecule with a target protein. Brucella's intracellular survival mechanism has not been studied with respect to SUMO-related proteins and Ubc9. Therefore, to investigate the relationship between Brucella melitensis 16M and SUMO, we constructed plasmids and cells lines suitable for overexpression and knockdown of SUMO1 and Ubc9 genes. Brucella 16M activated SUMO1/Ubc9 expression in a time-dependent manner, and Brucella 16M intracellular survival was inhibited by SUMO1/Ubc9 overexpression and promoted by SUMO1/Ubc9 depletion. In macrophages, Brucella 16M-dependent apoptosis and immune factors were induced by SUMO1/Ubc9 overexpression and restricted by SUMO1/Ubc9 depletion. We noted no effect on the expressions of SUMO1 and Ubc9 in B. melitensis 16M lipopolysaccharide-prestimulated mouse RAW264.7 macrophages. Additionally, intracellular survival of the 16M△VirB2 mutant was lower than that of Brucella 16M (p < 0.05). VirB2 can affect expression levels of Ubc9, thereby increasing intracellular survival of Brucella in macrophages at the late stage of infection. Collectively, our results demonstrate that B. melitensis 16M may use the VirB IV secretion system of Brucella to interact with SUMO-related proteins during infection of host cells, which interferes with SUMO function and promotes pathogen survival in host cells.
Animals ; Apoptosis ; Brucella melitensis ; Brucella ; Immunologic Factors ; Macrophages ; Mice ; Plasmids

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson's disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson's Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.
Adult ; Aged ; Brain Mapping ; Connectome ; Deep Brain Stimulation ; methods ; Female ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neural Pathways ; diagnostic imaging ; physiology ; Oxygen ; blood ; Parkinson Disease ; diagnostic imaging ; pathology ; therapy ; ROC Curve ; United Kingdom

Objective To evaluate the application of a self-designed handy body position scaffold in the fluoroscopy for lower limb surgery.Methods We reviewed the intraoperative X-ray films of 161 patients with lower limb fracture who had undergone intraoperative fluoroscopy using our self-made handy body position scaffold during surgery from October 2013 to May 2017.They were 105 males and 56 females,aged from 10 to 91 years (mean,39.7 years).There were 42 femoral fractures of middle or lower shaft,12 fractures of medial or lateral condyle or tibial plateau,96 tibiofibular fractures,7 ankle fractures and 4 foot fractures.The operation time,intraoperative fluoroscopy time,intraoperative bleeding,rate and time of fracture union,and complications were recorded.Results All the 161 patients completed intraoperative fluoroscopy and radiography uneventfully,indicating that the handy body position scaffold effectively maintained the body position of the affected ipsilateral lower limb.The body position scaffold was slightly deviated due to one overweight (121 kg) patient when the knee joint was flexed 90°,but the fluoroscopy and radiography was completed after adjustment of the C-arm roentgenographic machine.The operation time averaged 71.5 minutes (from 28 to 119 minutes),the X-ray exposure time 9.8 seconds (from 6 to 31 seconds),and the intraoperative bleeding 157.2 mL (from 80 to 500 mL).The 161 patients obtained follow-up for 5 to 22 months (average,14.1 months).The rate of primary union was 97.5％ (157/161).The time for fracture union averaged 8.8 weeks (from 4 to 17 weeks).Fracture nonunion occurred in one case,and delayed union in 3 cases.The final follow-ups revealed normal functional recovery of the affected knees and ankles,but no limb shortening,or no rotational,lateral or anteroposterior angulation deformity.Conclusion In the lower limb surgery,the intraoperative fluoroscopy can be completed better with the aid of our self-designed handy body position scaffold that prevents movement of the affected lower limb and lowers the risk of radiation exposure.