Objective:To investigate the clinical features and prognosis of multiple myeloma(MM)patients who resisted to the combination of bortezomib,lenalidomide and dexamethasone(VRD). Methods:The clinical features and prognosis of 150 patients with newly diagnosed MM in Beijing Chaoyang Hospital who were treated with VRD from January 2015 to January 2020 were retrospectively analyzed by SPSS software. Results:Among a total of 150 MM patients,21 patients resisted to VRD,including 14 patients with primary refractory to VRD and 7 patients with early relapse.In the VRD-resistant group(n=21),the median age of patients was 58 years(37-70 years),and female patients were more common(61.9％);Durie-Salmon stage:17 patients were DS stage Ⅲ,4 patients were DS stage Ⅱ;44.4％of those patients were cytogenetic high risk.CD20 positive rate was higher in the VRD-resistant group(P=0.014).The overall survival(OS)of MM patients in the VRD-resistant group was significantly lower than that in the VRD-nonresistant group(34 months vs not achieved,P＜0.001).In the VRD-resistant group,the median OS of MM patients receiving autologous hematopoietic stem cell transplantation was significantly longer than that of non-transplant patients(34 months vs 16 months,P=0.038).Drug resistance and non-autologous transplantation are independent adverse prognostic factors for newly diagnosed MM patients receiving VRD induction chemotherapy.COX multivariate analysis showed that age＞65,cytogenetic high risk and non-autologous stem cell transplantation may be adverse prognostic factors for VRD-resistant MM patients. Conclusion:Positive CD20 was more common in MM patients with VRD resistence,which may indicate more aggressive biological characteristics in VRD-resistent MM patients.The VRD-resistent MM patients had poor prognosis,they can obtain disease remission from salvage chemotherapy including daratumumab,and the survival of them also can be improved after autologous stem cell transplantation.

Copper plays a very important role in the physiological activities of the body. Copper metabolism disorders due to various reasons can disrupt the copper homeostasis of the body to cause a deficiency or excess of copper,resulting in a series of pathological processes that eventually lead to cell death and organ dysfunction. Cuproptosis,a newly discovered cell death mechanism,is related to copper overload. Cuproptosis has been confirmed in Wilson's disease,which is of great significance for future research on the mechanism and treatment of copper metabolism disorders.

Objective:To investigate clinicopathological features of 4 cases of intravascular large B-cell lymphoma (IVLBCL) .Methods:Clinical and pathological data were collected from 4 patients with histopathologically confirmed IVLBCL in Department of Dermatology, Peking Union Medical College Hospital from January 2020 to November 2020, and retrospectively analyzed.Results:The 4 patients were aged 57 - 76 years, including 2 males and 2 females. Of the 4 patients, all had neurological symptoms, 3 had fever, 3 exhibited impaired exercise tolerance and suffocation, and 3 exhibited pitting edema of the body. Case 1 presented with a cherry hemangioma-like papule measuring 0.2 cm in diameter on the back, and case 2 with telangiectasia on the left breast and upper abdomen. Six skin samples were taken from the 4 patients for histopathological and immunohistochemical studies, and tumor cells were found in 1 cherry hemangioma-like lesion and 1 lesion of telangiectasia, as well as in 2 of 4 normal skin samples. Histopathological findings mainly were dilated dermal blood vessels filled with large atypical mononuclear cells, and the atypical mononuclear cells were positive for CD20 immunohistochemically.Conclusion:For those patients with suspected IVLBCL, hemangioma-like and telangiectasia lesions tend to show characteristic histopathological and immunohistochemical findings, and a biopsy of normal skin can facilitate early diagnosis of IVLBCL.

Objective:To evaluate the effect of electroacupuncture (EA) on Golgi apparatus stress in the rats with endotoxin-induced acute lung injury (ALI).Methods:Twenty clean-grade male Sprague-Dawley rats, aged 2 months, weighing 160-185 g, were divided into 4 groups ( n=5 each) according to a random number table method: control group (C group), endotoxin group (LPS group), EA plus endotoxin group (EA+ LPS group), and sham EA plus endotoxin group (SEA+ LPS group).The model of endotoxin-induced ALI was developed by intravenous injection of lipopolysaccharide (LPS) 5 mg/kg in anesthetized animals.Bilateral Zusanli (ST36) and Neiguan (PC6) acupoints were stimulated with an electric stimulator for 30 min once a day at 1-4 days before and during model preparation in group EA+ LPS.In group SEA+ LPS, acupuncture needles were inserted to the surface of ST36 and PC6 acupoints with no current stimulation, and the other parameters were the same as those previously described in group EA+ LPS.Blood samples were collected from the abdominal aorta at 6 h after development of the model for measurement of concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum by enzyme-linked immunosorbent assay.The animals were sacrificed and lungs were removed for microscopic examination of the pathological changes of lung tissues (with a light microscope) and morphological changes of Golgi apparatus (with a transmission electron microscope) and for determination of wet to dry lung weight (W/D) ratio, cell apoptosis index (by TUNEL), activity of superoxide dismutase (SOD) (by WST-1 method), content of malondialdehyde (MDA) (by TBA method), and expression of Golgi matrix protein 130 (GM130), Golgin-84 and Golgi phosphoprotein 3 (GOLPH3) protein and mRNA in lung tissues (by Western blot or real-time polymerase chain reaction). Results:Compared with group C, the lung injury score, W/D ratio, cell apoptosis index, serum IL-6 and TNF-α concentrations and MDA content were significantly increased, SOD activity was decreased, the expression of GM130 and Golgin-84 protein and mRNA was down-regulated, the expression of GOLPH3 protein and mRNA was up-regulated ( P<0.05), and Golgi apparatus was swollen and vacuolated in the other three groups.Compared with group LPS, lung injury score, W/D ratio, cell apoptosis index, serum IL-6 and TNF-α concentrations and MDA content were significantly decreased, SOD activity was increased, the expression of GM130 and Golgin-84 protein and mRNA was up-regulated, the expression of GOLPH3 protein and mRNA was down-regulated ( P<0.05), and swelling and vacuolization of Golgi apparatus were reduced in group EA+ LPS, and no significant change was found in the parameters mentioned above in group SEA+ LPS ( P>0.05). Conclusions:The mechanism by which EA reduces endotoxin-induced ALI may be related to inhibition of Golgi apparatus stress in lung tissues of rats.

Objective:To investigate the effects of deep learning-based AiContour ??versus atlas-based Raystation ?? automatic contouring methods on the contouring of organs-at-risk on CT images of patients with rectal cancer who undergo radiotherapy, providing evidence for clinical application. Methods:Fifty patients with rectal cancer who received treatment during January to June 2020 in Zhejiang Provincial People's Hospital (Affiliated Hospital of Hangzhou Medical College) were included in this study. The CT images from 20 patients with rectal cancer that had been contoured by experienced radiotherapist were selected as target images and automatically contoured using the data template library of AiContour ?? and Raystation ?? automatic contouring methods. Hausdorff distance, mean distance to agreement, dice similarity coefficient, Jaccard coefficient were used to quantitatively evaluate the accuracy of the volume of contour of organs-at-risk automatically sketched by the two methods. Results:There was no significant difference in Hausdorff distance in left femoral head [(6.81 ± 2.66) vs. (7.24 ± 2.10)], right femoral head [(7.38 ± 3.91) vs. (8.14 ± 3.71)], pelvis [(24.00 ± 9.01) vs. (24.66 ± 9.67)] between AiContour ?? and Raystation ?? automatic contouring methods ( tleft femoral head = -0.831, tright femoral head = -0.821, tpelvis = -0.357, all P > 0.05). Significant differences were observed in mean distance to agreement, dice similarity coefficient and Jaccard coefficient of organs-at-risk (all P < 0.05). The mean values of dice similarity coefficient automatically sketched by AiContour ?? method were > 0.7. The DSC of left kidney, right kidney, rectum and bladder automatically sketched by Raystation ?? method were < 0.7, and the dice similarity coefficient values of other organs-at-risk automatically sketched by Raystation ?? method were > 0.7. In addition, Hausdorff distance, mean distance to agreement and Jaccard coefficient values of organs-at-risk automatically sketched by AiContour ?? method were superior to those automatically sketched by Raystation ??. Conclusion:After slight modification, the organs-at-risk automatically sketched by AiContour ?? and Raystation ?? methods can meet clinical requirement. The contouring effects provided byAiContour ?? method were superior to those provided by Raystation ?? method.

OBJECTIVE: To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism. METHODS: Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene. RESULTS: The proband carried a compound heterozygous mutation in the SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c.1295A>G (p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G [p.N432S]) to be harmful. Compared to the mother, expression of SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, SIK3 expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that Sik3 gene has a marked higher level of expression in the brain. CONCLUSION The SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.
Animals ; Autism Spectrum Disorder/genetics* ; Epilepsy/genetics* ; Male ; Mice ; Mutation ; Mutation, Missense ; Protein Kinases ; Protein Serine-Threonine Kinases/genetics* ; Whole Exome Sequencing

Objective:To study whether aspirin has inhibitory effect on microglia activation induced by Poly-IC and its mechanism.Methods:Microglia cell line BV2 were cultured in vitro to establish a Poly-IC stimulation-induced microglia cell immune activation model. The experiment groups were divided into control group (no treatment), model group (Poly-IC 10 μg/ml), high dose aspirin group (1 mmol/L aspirin), low dose aspirin group (0.1 mmol/L aspirin), high dose aspirin pretreatment group (Poly-IC 10 μg/ml + 1 mmol/L aspirin) and low dose aspirin pretreatment group (Poly-IC 10 μg/ml + 0.1 mmol/L aspirin). The phagocytosis ability of microglia cells, reactive oxygen species (ROS) and Iba1 protein expression were detected by using immunofluorescence method. The expression of the inflammatory cytokines Il-1β, Il-6, Il-10, TNF-α and cox-2 mRNA in microglia cells were detected by real-time quantitative PCR (RT-qPCR).Results:Compared with the control group, the morphology of microglia cells in model group changed significantly, and the phagocytosis ability and production of reactive oxygen species (ROS) increased. At the meantime, the expression of Iba1 protein was strongly decreased. In the model group, The mRNA expressions of IL-1β(20.55±1.92), IL-6 (63.98±7.83), TNF-α (16.84±3.19), COX-2 (6.78±0.42) were higher than IL-1β(1.01±0.14), IL-6 (0.95±0.17), TNF-α (1.22±0.38), COX-2 (0.87±0.11) in the control group. (Il-1β ( t=26.14), Il-6 ( t=10.22), TNF-α ( t=17.06) and COX-2 ( t=37.07), all P<0.01). In the aspirin pretreatment group, the phagocytic ability of microglia cells was inhibited compared with the model group, and the production of reactive oxygen species (ROS) reduced. The expression of Iba1 protein was also partly recovered. Meanwhile, the effect of the high aspirin dose pretreatment group on pro-inflammatory factors IL-1β(9.95±0.52), IL-6 (39.64±6.89), TNF-α(1.57±0.42), COX-2 (2.47±0.14)were lower than those in the model group significantly.(IL-1β: t=14.18, IL-6: t=3.69, TNF-α: t=16.68, COX-2: t=27.03, all P<0.01). Conclusion:Aspirin has an inhibitory effect on microglial activation induced by Poly-IC, which may be related with inhibiting the expression of inflammatory factors.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

Objective: This study investigated the efficacy and safety of a combination of lenalidomide, bortezomib, and dexametha-sone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical features and responses of 48 patients with NDMM who were treated with RVD from January 2015 to May 2019 in Beijing Chaoyang Hospital were retrospectively analyzed. Results: The median age of the 48 patients was 59 years (range: 34-79). Among these, 44 patients were Durie-Salmon stageⅢ, 15 were ISS stageⅡ, 19 were ISS stageⅢ, and 12 had plasmacytoma; 32.5% of all patients were cytogenetic high-risk. All patients re-ceived a median of four cycles (range: 1-9) of the RVD regimen as induction treatment. The overall response rate was 97.9%, with 35.4% of patients achieving complete response (CR) or better. The rate of very good partial remission (VGPR) or better was increased from 64.1% (after two cycles) to 84.6% (after four cycles). The mean collection of CD34+cells was 4.2 (± 2.6)×106/kg. Negative minimal residual disease (MRD), as indicated by next-generation flow (NGF), was achieved in 20.6% of patients after induction. Two patients with positive MRD after induction became MRD negative after transplantation. Two patients developed grade 3 or 4 hematologic toxic-ity. No nonhematologic toxicity of grade 3 or 4 was observed. Conclusions: In patients with NDMM, RVD treatment resulted in signifi-cantly improved response rates and exhibited an acceptable risk-benefit profile, with no adverse impact on stem cell collection. RVD combined with transplantation significantly improved the negative rate of MRD, as indicated by NGF.

Objective: To investigate the effect of nutritional risk screening tool (NRS-2002) upon the clinical efficacy and survival outcomes in patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) receiving concurrent chemoradiotherapy. Methods: Clinical data of 105 LAESCC patients treated with concurrent chemoradiotherapy in Zhejiang Provincial People′s Hospital from January 2013 to December 2015 were retrospectively analyzed. Nutritional status screening was performed using the NRS-2002 scale. The rate comparison was analyzed by using chi-square test. Kaplan-Meier survival analysis was adopted to calculate the survival rate. Log-rank test was utilized to statistically analyze the differences in survival outcomes. Cox regression model was used for uni-and multi-variate analyses. Results: Prior to concurrent chemoradiotherapy, 37.1% of patients had the nutritional risk. Patients with NRS-2002 score ≥3 had a significantly higher incidence of ≥ grade 3 toxic reactions compared with their counterparts obtaining NRS-2002 score of 1-2(P=0.007). The median overall survival (OS) and progression-free survival (PFS) of all patients were 17.0 and 11.8 months. The OS and PFS of patients with NRS-2002 score ≥ 3 were significantly lower than those of their counterparts obtaining NRS-2002 score of 1-2(both P=0.000). Multivariate analysis demonstrated that NRS-2002 score of ≥3 was an independent prognostic factor for OS (P=0.000) and PFS (P=0.001). Conclusions NRS-2002 tool reveals that patients with esophageal cancer possess a relatively high nutritional risk. Prior to treatment, NRS-2002 score of ≥3 is significantly correlated with an increasing risk of toxic reactions and decreasing survival rate, which is worthy of subsequent investigation.