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【Objective】 To evaluate the clinical efficacy and prognostic factors in multiple myeloma (MM) patients treated with autologous hematopoietic stem cell transplantation (auto-HSCT). 【Methods】 The clinical data of 155 MM patients newly diagnosed and suitable for transplantation in our hospital from 2014 to 2021 were retrospectively analyzed. They were divided into auto-HSCT group and non-auto-HSCT group according to the treatment mode. The clinical efficacy, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Furthermore, the prognostic factors of auto-HSCT group were analyzed. 【Results】 ① There were 51 patients in auto-HSCT group and 104 patients in non-auto-HSCT group. There was no statistical difference in baseline characteristics except age between the two groups. ② Hematopoietic reconstruction was achieved in all patients in auto-HSCT group, and no transplantation-related mortality was found. ③ The clinical efficacy of pre-and post-transplantation was compared in auto-HSCT group. sCR/CR rate was significantly increased after transplantation (P=0.041). The effective remission rate (≥VGPR) was also higher (P=0.05). As for the best efficacy, sCR/CR rate and effective remission rate were both significantly higher in auto-HSCT group than in non-auto-HSCT group (P=0.001). ④ In auto-HSCT group, by the end of follow-up, the median OS was not reached, the median PFS was 30.5 months, and 3-year OS and PFS was 87% and 40.3%, respectively. In non-auto-HSCT group, the median OS was 61 months, the median PFS was 21 months, and 3-year OS and PFS was 65.3% and 33.1%, respectively. It indicated that OS was significantly prolonged in auto-HSCT group (P=0.004). PFS was also prolonged but without significant difference (P=0.065). ⑤ Analysis of prognostic factors in auto-HSCT group showed that decreased PLT (P=0.038) and increased serum-adjusted calcium (P=0.017) were independent risk factors for OS, decreased PLT (P=0.005), female (P=0.018) and disease status of PR or worse before transplantation (P=0.012) were independent risk factors for PFS. 【Conclusion】 Auto-HSCT can improve the remission rate, prolong OS in MM patients, and possibly prolong PFS. Increased serum-corrected calcium and decreased PLT are independent prognostic factors for OS in patients treated with auto-HSCT. Decreased PLT, female, and disease status of PR or worse before transplantation are independent prognostic factors for PFS.
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Anaplastic thyroid cancer (ATC) is a rare malignancy, accounting for 1%-2% of all thyroid cancers, however, ATC accounts for the majority of deaths from thyroid cancer. Currently, the main comprehensive treatments are surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy. Based on the latest American Thyroid Association guidelines and the related literatures, we summarize the most reasonable and effective therapeutic strategies to improve the survival rate of patients with ATC as well as the quality of life.
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Objective:To investigate the association of abdominal fat distribution with glycolipid metabolism and diabetic complications in patients with T2DM.Methods:Totally 357 inpatients with T2DM were collected from the Endocrinology Department of our hospital. All patients received quantitative computed tomography to measure the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and were divided into three groups depending on the tertile of VAT value: T1 group (VAT<162.0 cm 2), T2 group (162.0≤VAT<221.1 cm 2), T3 group (VAT≥221.1 cm 2). The incidences of diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy, peripheral atherosclerosis, and cardia-cerebrovascular disease were examined in all patients. Results:HbA 1C level in T1 group was higher than that in T3 group( P<0.05). High density lipoprotein-cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) in T1 group were higher compared with those in T2 and T3 groups ( P<0.05). Male proportion, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), 24h urinary albumin, diabetic kidney disease and peripheral atherosclerosis in T2 and T3 groups were higher than those in T1 group ( P<0.05). Fasting C- peptide (FCP) and modified homeostasis model assessment for insulin resistance (HOMA-IR) in T3 group were higher than those in T1 and T2 group ( P<0.01). VAT and SAT were positively correlated with BMI, FCP, and HOMA-IR (p<0.01). VAT was positively correlated with age, SBP, DBP, TG, 24h urinary albumin, diabetic kidney disease, peripheral atherosclerosis, and cardia-cerebrovascular disease ( P<0.05), while inversely correlated with HbA 1C, HDL-C, and eGFR ( P<0.05). SAT was positively correlated with total cholesterol and low density lipoprotein-cholesterol ( P<0.01), while negatively correlated with peripheral atherosclerosis ( P<0.01). Multivariate logistic regression analysis showed that VAT was still a risk factor for diabetic kidney disease after adjusted by age, BMI, SBP and fasting plasma glucose( P=0.013). Conclusion:VAT and SAT are associated with blood lipids and insulin resistance, while VAT seems to be a risk factor for diabetic kidney disease.
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Objective@#To compare the abdominal fat distribution in patients with primary aldosteronism (PA) and essential hypertension (EH), and to analyze the correlation between abdominal fat area and indexes such as glycolipid metabolism and insulin resistance.@*Methods@#Forty-five PA and 55 EH patients were collected from inpatients in the First Affiliated Hospital of Zhengzhou University for suspicious secondary hypertension, from September 2016 to February 2019. All patients received quantitative computed tomography to measure the total abdominal fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) when receiving adrenal CT detection. Visceral obesity was defined as VFA≥130 cm2. The percentage of visceral fat area in total abdominal fat area (V%=VFA/TFA), the ratio of visceral fat area to subcutaneous fat area (V/S=VFA/SFA) and the percentage of visceral obesity were calculated.@*Results@#TFA and VFA in EH group were higher than those in PA group matched by age, gender, and body mass index (BMI, all P<0.01), and there were no statistically significant differences in SFA, V%, V/S, and the percentage of visceral obesity between the two groups. In PA group, TFA and VFA were positively correlated with homeostasis model assessment of insulin resistance index (P<0.01), TFA was positively correlated with triglycerides (TG) and low density lipoprotein-cholesterol, while SFA was positively correlated with TG (all P<0.05).@*Conclusion@#Compared with EH patients matched by age, gender, and BMI, TFA and VFA in PA patients are lower. Abdominal fat area is associated with insulin resistance and blood lipids in PA patients, while VFA exerts a greater effect on insulin resistance than that of TFA and SFA.
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Objective To compare the abdominal fat distribution in patients with primary aldosteronism (PA) and essential hypertension (EH), and to analyze the correlation between abdominal fat area and indexes such as glycolipid metabolism and insulin resistance. Methods Forty-five PA and 55 EH patients were collected from inpatients in the First Affiliated Hospital of Zhengzhou University for suspicious secondary hypertension, from September 2016 to February 2019. All patients accepted quantitative computed tomography to measure the total abdominal fat area ( TFA), visceral fat area ( VFA), and subcutaneous fat area ( SFA) when accepted adrenal CT detection. Visceral obesity was defined as VFA≥130 cm2. The percentage of visceral fat area in total abdominal fat area (V%=VFA/TFA), the ratio of visceral fat area to subcutaneous fat area (V/S=VFA/SFA) and the percentage of visceral obesity were calculated. Results TFA and VFA in EH group were higher than those in PA group matched by age, gender, and body mass index (BMI, all P＜0.01), and there were without statistically significant differences in SFA, V%, V/S, and the percentage of visceral obesity between the two groups. In PA group, TFA and VFA were positively correlated with homeostasis model assessment of insulin resistance index ( P＜0. 01), TFA was positively correlated with triglycerides ( TG) and low density lipoprotein-cholesterol, while SFA was positively correlated with TG (all P＜0.05). Conclusion Compared with EH patients matched by age, gender, and BMI, TFA and VFA in PA patients are lower. Abdominal fat area is associated with insulin resistance and blood lipids in PA patients, while VFA exerts a greater effect on insulin resistance than that of TFA and SFA.
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Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
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Familial partial lipodystrophy type 2 (FPLD2) is an autosomal dominant disorder caused by mutations in LMNA gene,which is characterized by adolescent onset selective subcutaneous fat loss with metabolic abnormalities such as insulin resistance.Severe insulin resistance can cause acanthosis nigricans,pseudoacromegaly,ovarian dysfunction,glucose,and lipid metabolism disorders.Therefore,it is often misdiagnosed as metabolic syndrome,type 2 diabetes,polycystic ovary syndrome,acromegaly,and Cushing's syndrome.Through the analysis of the diagnosis and treatment of a case of FPLD2 with acromegaly,and the importance of tracing the origin of the disease is emphasized and also does the role of genetic testing in diagnosis.It suggests that clinicians should pay attention to the fat distribution of those similar patients,and make diagnosis and treatment timely.
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Objective To screen the optimal RNA interference sequence of acute monocytic leukemia associated antigen 22 (MLAA-22) gene in order to study gene function of it. Methods MLAA-22 coding sequence (CDS) was cloned by reverse transcription polymerase chain reaction (RT-PCR) and the CDS was inserted in to pEGFP-N1-3FLAG vector to construct eukaryotic expression vector of MLAA-22. At the same time, four RNA interference sequences were designed and cloned to the vector. Expression vector and RNA interference vector were co-transfected into 293T cells, and the optimal RNA interference sequence was screened by fluorescence and Western blot analyses. Results MLAA-22 eukaryotic expression vector pEGFP-N1-3FLAG and four RNA interference vectors were successfully constructed. After co-transfected 293T cells, KD2 was selected as the optimal interference sequence of MLAA-22. Conclusion KD2 is an optimal interference sequence for targeting MLAA-22 antigen gene.
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Objective To make the chromosome karyotype analysis of 130 patients with leukemia by using the improved chromosome short-term culture method.Methods We optimized the main factors with a single factor gradient experiment in short-term culture of bone marrow chromosome, including colchicines concentration, duration of action of colchicines,and hypotonic time.On this basis,we conducted the three-factors and three-level orthogonal experiment to achieve improved bone marrow chromosome preparation system,which was later applied in 130 patients with leukemia in our hospital.Results The orthogonal experiment results showed that the optimum conditions were colchicines concentration of 0.07 μg/mL,colchicines action time of 80 min,and hypotonic time of 35 min during the preparation of the bone marrow chromosome.Using this method,the chromosome preparation success rate reached 97.69% and the detection rate of abnormal karyotype reached 82.3% in the chromosome karyotype analysis.Conclusion Bone marrow chromosome preparation system with colchicines concentration of 0.07 μg/mL and colchicines action time of 80 min,and hypotonic time of 35 min is worthy of clinical promotion.
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Objective To explore the prognostic value of modified Glasgow prognostic score (mGPS) and risk factors in predicting overall survival (OS) in the castrate-resistant prostate cancer (CRPC) treated with docetaxel-based chemotherapy.Methods We retrospectively analyzed the data of 48 consecutive Chinese patients with CRPC received docetaxel-based chemotherapy in our institution from January 2008 to January 2012.Patients were divided into three groups according to the mGPS:0,1 and 2 score groups,and compare the OS among the three groups.Variables that were influenced the efficacy of chemotherapy were included in the univariate analysis and multivariate model.Survival analysis was performed using Kaplan-Meier curves,and the differences in overall survival rates were assessed using the Logrank test.Results The follow-up was performed until April 2014.There were 48 CRPC patients including mGPS 0 score group 30 cases,mGPS 1 score group 11 cases and mGPS 2 score 7 cases.The median OS was 22,11,9 months,respectively,P＜0.01.Univariate analysis showed that:prechemotherapy baseline total prostate-specific antigen (tPSA),Eastern Cooperative Oncology Group (ECOG) score,the number of chemotherapy cycle,visceral metastasis and PSA response were associated with poor prognosis (P＜0.05).Multivariate analysis showed that:prechemotherapy mGPS 1-2 score,baseline tPSA＞60 μg/L,the number of cycles of chemotherapy≤5,with visceral metastasis and PSA response in patients with CRPC were independent risk factors for prognosis in the CRPC treated with docetaxel-based chemotherapy.Conclusion mGPS is an independent risk factor for prognosis in the CRPC patients treated with docetaxel-based chemotherapy.
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Objective To propose an optimal therapeutic scheme, finite element analysis was used to evaluate the biome?chanical status of femoral head under daily activities. Methods Non?necrotic femoral head volunteers (11 people) and necrotic femoral head patients (7 cases) were included in this study. All these participants were divided into two groups:control group and abnormal group. The DICOM imaging files of each participant were imported into ScanIP software to form a mask showing the prox?imal femurs. Then the finite element models of proximal femurs were progressively reconstructed. The generated models were im?ported into Abaqus, and the forces were added on these models to simulate daily activities, including standing, sitting, upstairs, and squatting etc. The loads and boundary conditions of digital daily activities simulation were collected from Orthoload database. All of the femoral finite element models were progressed in Abaqus under above activity conditions. After the models were pro?cessed, stress concentrating region was defined in each models respectively, which expressed the main bearing structure in each model based on the result of finite element analysis. At last, the elastic modulus (E?modulus) and strain of the stress concentrating region in each femoral model were extracted and calculated. Results There was no significant difference in age, weight, and height between these two groups. In control group, no significant differences of E?modulus (7 125±745 MPa on left, and 7 112±751 MPa on right) and strain (micro?strain:952 on left, and 954 on right)were found between their bilateral proximal femurs;however in abnormal group, the patients' E?modulus (5 798±1036 MPa on normal side, and 6 667±888 MPa on necrotic side) and strain (mi?cro?strain:1 261 on normal side, and 987 on necrotic side) of necrotic side were significantly lower than normal side. As to all the daily activities which were considered in this study, in abnormal group, the E?modulus among each postures of abnormal side were significantly lower than the E?modules of healthy side;the micro?strain in downstairs was also significantly lower than other pos?tures. Conclusion Daily activities with different intensity could generate different mechanical effects on femoral head, espe?cially on necrotic femoral head. The higher intensity of posture, the greater damage would be found in necrotic femoral head.
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Multiple myeloma is common in the older population and is treated mainly with chemotherapy. However, chemotherapy-related side effects imitate the clinical manifestations of Sheehan's syndrome, which leads to misdiagnosis and missed diagnosis, particularly for older patients without a clear history of postpartum hemorrhage. Therefore, when older women with malignant myelomas show refractory hyponatremia and gastrointestinal disorders while under chemotherapy, a diagnosis of Sheehan's syndrome should be considered. The early detection of the disorder will guarantee timely individualized treatment.
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[Objective]To discuss the clinical effect of fludarabine and busulfan (Bu+Flu) as a low toxicity myeloablative conditioning regimen for allogeneic peripheral blood stem cell transplantation (allo-HSCT)in leukemia patients.[Methods]Clinical data of 13 patients with hematological malignancies receiving conditioning regimen with Bu+Flu for allo-HSCT were analyzed retrospectively.Conditioning regimen was Bu+Flu,compalriot mismatched and unrelated transplantation combined with rabbit anti-human thymocytes immune globulin (ATG).CsA+short course of methotrexate or CsA + mycophenolate mofetil were used to prevent graft-versus-host disease (GVHD).DNA sequencing of short tandem repeat (STR)polymorphism analysis method was performed for identification of donor stem cells implantation.[Results]13 patients all tolerated with this conditioning regimen well,no serious complications occurred.Neutrophil engraftment was at 9-15 days (median 11 days),platelet engraftment at 8-25 days (median 13 days).10 patients achieved hematopoiesis reconstitution with their full donor chimerisms confirmed by STR-DNA analysis.Acute GVHD occurred in 5 cases,accounting for 38.5％.Chronic GVHD occurred in 4 cases of 10 patients could be assessed,accounting for 40.0％.Severe GVHD more than Ⅱ degree did not happen.1-39 months (median time 11 months)of follow-up revealed the overall survival rate of 76.9％(10/13),disease-free survival of 61.5％ (8/13).The causes for death were relapse in all.[Conclusion]The conditioning regimen with Bu+Flu has low toxicity,well tolerance and better effect.
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Objective To investigate the effect of endoplasmic reticulum stress (ERS)-associated apoptosis on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) in rats. Methods Eighteen healthy male Wistar rats undergoing UUO were sacrificed at 3,7,14 days after operation. Additional seven rats underwent sham operation. Histological changes were observed by HE and Masson staining. Immunohistochemistry was performed on renal tissue for α-smooth muscle actin (α-SMA). Chromatometry was used to detect the content of hydroxyproline. Apoptosis cells were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the electrophoresis analysis of genome DNA. The mRNA expression of glucose-regulated protein 78 (GRP78), which are important markers of ERS, were detected by RT-PCR. Western blotting was used to assess the protein level of GRP78 and cysteinyl aspartate specific proteinase-3 (caspase-3). Results Compared with sham operation group, the degree of renal interstitial and the level of hydroxyproline content of UUO group increased significantly (P<0.05). Immunohistochemistry staining indicated that a-SMA extensively expressed in renal tubular and interstitial cells. The apoptotic cells in the renal tubular and interstitium were continuously increased from day 3 to the end of experiment of UUO group. As early as 3 days after surgery, the mRNA level of GRP78 in UUO group increased compared with sham operation group (P<0.01), while the protein expression increased on day 7 after surgery (P<0.01). Prolonged ERS triggered apoptosis, the protein expression of caspase-3 increased significantly on day 3 after surgery (P< 0.05), and the expression sustained high level during the experiment afterwards. There was a positive correlation between GRP78 protein expression and hydroxyproline content (r =0.657, P< 0.01) as well as caspase-3 protein expression (r=0.714, P<0.01). Conclusions UUO induces a significant up-regulation in endoplasmic reticulum molecular chaperones at early stage, indicating that ERS response is activated in the rat kidney. Prolonged ERS can lead to renal tubular and interstitial cell apoptosis, and caspase-3-mediated ERS associated apoptosis may contribute to the fibrosis.
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OBJECTIVE:To study the safety and efficacy of Neuroform self-expanding stent for symptomatic intracranial artery stenosis.METHODS:A total of 37 patients with symptomatic intracranial artery stenosis received treatment at the Department of Neurosurgery,Affiliated Hospital of Behua University and Xuanwu Hospital were selected,who were ineffective to anticoagulation and antiplatelet treatment,including 24 males and 13 females,aged from 49 to 72 years,mean aged 64 years.All patients were received Neuroform self-expanding stent following angiography.RESULTS:All patients underwent PTAS with mean preoperative stenosis were reduced from 64% to 24% after percutaneous transluminal angioplasty (PTAS).The technically successful rate was 100%.All the patients were received a 6-22 month follow-up (average 13 months).The average artery stents was retrieved by 50%-90% after stent deployment.There was no arterial dissection,acute occlusion of the target artery or symptomatic distal emboli.Within the follow-up period,1 patient endured asymptomatical artery full occlusion.Two stents were implanted simultaneously in 3 patients,1 of them suffered bilateral vertebral artery stenosis,and 2 had right vertebral arterial and basilar artery stenosis.One patient suffered acute in-stent thrombosis and recovered after thrombolytic therapy.No pathogenetic condition was aggravated in the follow-up.CONCLUSION:The application of Neuroform self-expanding stent can alleviate the ischemic symptoms of patients with vertebrobasilar stenosis and elevate the operative safety and effectiveness.However,further study is needed to evaluate the long-term therapeutic effect.
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Objective To investigate the effects of oxidative stress on the expressions of transforming growth factor-?1(TGF-?1) and transforming growth factor-? receptor Ⅰ(TGF-?RⅠ) in rat unilateral ureteral obstruction(UUO) models.Methods Thirfty Wistar rats were randomly assigned into three groups:SOR group(sham-operated group,n=7);UUO group(operation group,n=11);US group(spironolactone 50 mg?kg-1?d-1 by daily gastric gavage after UUO,n=12).All the rats were killed 14 d after surgery.Renal fibrosis was assessed by the determination of tissue hydroxyproline(HYP) content.Malondialdehyde(MDA),superoxide dismutase(SOD) as well as aldosterone(ALD) content were measured.Histological changes were observed by HE and Masson staining.Immunohistochemistry was performed to detect the expressions of TGF-?1 and TGF-?RⅠ.Western blotting was used the determine the expression of TGF?RⅠ protein.Results Compared with sham group,the ALD contents in plasma and kidney tissues in UUO group significantly increased(P
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Objective To construct an expression vector directed by hU_(6)snRNA promoter for synthesizing small RNA and to identify its functional activity in the gastric carcinoma cells——SGC-7901.Methods Using human genomic DNA as template,U_(6) snRNA promoter was obtained by PCR method,and then cloned into PUC19 vector to produce the recombinant plasmid PUC-hU_6-extra,which was sequenced and then transfected into gastric carcinoma cell——SGC-7901 with liposome.The effect of expression directed by U_6 promoter was detected by RT-PCR method,and the cell proliferation curve analysis was performed by stained dye.Results The hU_6 snRNA promoter with the first 27 nucleotides followed were successfully cloned into PUC19 plasmid.The recombinant vector could efficiently transcribe small RNA molecules and exerted no effect on cell proliferation in SGC-7901 cells in vitro.Conclusion We have successfully constructed the recombinant PUC-hU_6-extra plasmid vector that can efficiently transcribe small RNA molecules directed by hU_6 snRNA promoter in the gastric carcinoma cells——SGC-7901.