Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Objective To evaluate the safety and efficacy of endoscopic ultrasound (EUS) guided ethanol ablation of benign insulinoma and compare its' advantages and disadvantages with surgical treatment. Methods From April 2011 to February 2016, clinical data of 38 patients with benign insulinoma treated by EUS-guided ethanol ablation or surgical treatment were retrospectively analyzed. Results 97.4% (37/38) patients had a typical clinical manifestation of Whipple's triad, and the I/G ratio of 82.9% patients (29/35) was more than 0.3 with their onset of hypoglycemia. The positive preoperative etiologic diagnosis rates of transabdominal ultrasonography, CT, MRI, PET/CT and EUS were 50.0%, 67.6%, 66.7%, 75.0%, 89.7% respectively. In the current study, 18 patients underwent EUS-guided ethanol ablation (EUS-FNI group) and 20 patients received surgicaltreatment (surgical group). Compared with the surgical group, the operation time, intraoperative hemorrhage volume, postoperative complications, length of stay and hospitalization costs were significantly reduced in the EUS-FNI group (P < 0.05). No treatment-related complications was observed in EUS-FNI group, while 40.0% (8/20) patients in surgical group had complications. During the follow-up period, all these patients maintained stable blood glucose without taking medication, and there's no recurrence of insulinoma in EUS-FNI group after the last treatment with alcohol injection; In surgical group, only 90.0% (18/20) patients had no recurrence, episode of hypoglycemia was less after the operation in 10.0% (2/20) patients. Conclusion EUS-guided ethanol ablation of benign insulinoma is safe and effective, compared with traditional surgical treatment, EUS-guided ethanol ablation is minimally invasive, costs less, recovers fast after treatment and has fewer complications.

Objective To evaluate the safety and efficacy of endoscopic ultrasonography(EUS) guided ethanol ablation in patients with insulinoma. Methods The data of 10 patients with insulinoma trea-ted at the First Affiliated Hospital of Guangxi Medical University from December 2013 to January 2015 were prospectively analyzed. Results The patients were given EUS-guided ethanol ablation with dose of 0. 10 to 2. 00 ml(average 0. 70 ± 0. 62 ml)in pancreatic lesions for 15 times. No complications were observed dur-ing and after the procedure. The blood glucose improved after the procedure[4. 8(3. 9-5. 5)mmol/ L VS 2. 4 (1. 9-2. 5)mmol/ L,P < 0. 05]and the serum insulin level significantly decreased[83. 7(40. 1-143. 5) pmol/ L VS 177. 3(66. 5-200. 6)pmol/ L,P<0. 05]. The average hospital stay was(4. 3±1. 5)days. The patients were followed up for 6-12 months. EUS indicated that the echo of pancreatic lesions changed from high to low. CE-EUS revealed low enhancement and lack of blood supply. Conclusion EUS-guided ethanol ablation may become a promising minimally invasive treatment for insulinoma because of its safety,efficacy and low price. Trail registration Clinical Trial.gov,NCT02121366.

OBJECTIVETo investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma.

METHODSClinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed.

RESULTSThe expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival.

CONCLUSIONNeuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.

Adenocarcinoma ; diagnosis ; pathology ; Biomarkers, Tumor ; metabolism ; Chromogranin A ; metabolism ; Disease Progression ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Secretagogins ; metabolism ; Stomach Neoplasms ; diagnosis ; pathology ; Synaptophysin ; metabolism

Objective To detect the serum expression level of Pokemon and explore its clinical value combines with AFP,AFP-L3 or DCP in hepatocellular carcinoma (HCC).Methods In this study,the serum levels of Pokemon,AFP,AFP-L3 and DCP in 30 patients with HCC,34 patients with benign liver diseases and 30 healthy controls were examined by enzyme-linked immunosorbent assay.Then,the clinical significance of Pokemon expression level was analyzed.In the end,the diagnostic evaluation of four serum biomarker alone detection was used to analyze the sensitivity,specificity,the area under the curve and Youden index in the diagnosis of HCC.Results The serum expression level of Pokemon in patients with HCC was (22.63 ± 6.82) ng/ml,which was significantly higher than that in the group with benign liver diseases and healthy controls [(3.54±1.26)ng/ml,t =8.594,P＜0.001;(1.95 ±0.57)ng/ml,t =10.021,P＜0.001].The expression level of Pokemon in HCC patients was correlated to tumor size (t =2.678,P =0.021) and TNM stag (t =2.578,P =0.034).The serum expression levels of AFP,AFP-L3 and DCP in patients with HCC were (774.56 ± 96.52) ng/ml,(26.37 ± 2.54) ng/ml and (93.49 ± 30.45) mAU/ml,which were significantly higher than those in the group with benign liver diseases [(22.21 ± 3.57) ng/ml,(7.05 ± 2.71) ng/ml,(34.68 ± 10.13) mAU/ml] and healthy controls [(14.65 ± 4.45) ng/ml,(3.84 ± 1.09) ng/ml,(25.87 ± 9.01)mAU/ml,F=58.46,P=0.000;F=12.47,P=0.000;F=23.41,P=0.000].The sensitivity and specificity of Pokemon,AFP,AFP-L3,DCP in the diagnosis of HCC were 84.6％ and 87.5％,52.5％ and 78.9％,95.0％ and 80.0％,77.1％ and 87.5％,respectively.Conclusion The enhanced Pokemon serum level,with its sensitivity and specificity higher than AFP,points out Pokemon may be a potentially useful biomarker to diagnose HCC.

PURPOSE: Several accelerated partial breast irradiation (APBI) techniques are being investigated in patients with early-stage breast cancer. The present study evaluated the feasibility, early toxicity, initial efficacy, and cosmetic outcomes of accelerated partial breast intensity-modulated radiotherapy (IMRT) for Chinese female patients with early-stage breast cancer after breast-conserving surgery. METHODS: A total of 38 patients met the inclusion criteria and an accelerated partial breast intensity-modulated radiotherapy (APBI-IMRT) plan was designed for each patient. The prescription dose was 34 Gy in 10 fractions, 3.4 Gy per fraction, twice a day, in intervals of more than 6 hours. RESULTS: Of the 38 patients, six patients did not meet the planning criteria. The remaining 32 patients received APBI-IMRT with a mean target volume conformity index of 0.67 and a dose homogeneity index of 1.06. The median follow-up time was 53 months and no local recurrence or distant metastasis was detected. The most common acute toxicities observed within 3 months after radiotherapy were erythema, breast edema, pigmentation, and pain in the irradiated location, among which 43.8%, 12.5%, 31.3%, and 28.1% were grade 1 toxicities, respectively. The most common late toxicities occurring after 3 months until the end of the follow-up period were breast edema, pigmentation, pain in the irradiated location, and subcutaneous fibrosis, among which 6.2%, 28.1%, 21.9%, and 37.5% were grade 1 toxicities, respectively. Thirty-one patients (96.8%) had fine or excellent cosmetic outcomes, and only one patient had a poor cosmetic outcome. CONCLUSION: It is feasible for Chinese females to receive APBI-IMRT after breast conserving surgery. The radiotherapeutic toxicity is acceptable, and both the initial efficacy and cosmetic outcomes are good.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; Edema ; Erythema ; Female ; Fibrosis ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Neoplasm Metastasis ; Pigmentation ; Prescriptions ; Radiotherapy ; Radiotherapy, Intensity-Modulated* ; Recurrence

In previous study,glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro.In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism,34 male pups were randomly assigned to NS group,low dose GA (LGA,5 μmol GA/g body weight) group and high dose GA (HGA,10 μmol GA/g body weight) group.These pups were subcutaneously administered with three injections from postnatal day 3 to 22 at 7:30 am,15:00 pm and 22:30 pm and killed 12 h after the last injection.Microscopic pathology in corpus striatum was evaluated by HE staining.The apoptotic cells were identified by TUNEL staining.The transcript levels of caspase-3,8,9,Bax,Bcl-2 were detected by using real-time PCR and the protein levels of procaspase-3 and the active fraction were evaluated by Westem blotting.In LGA and HGA groups,ventricle collapse,cortical atrophy by a macroscope and interstitial edema,vacuolations,widened perivascular space of bilateral striatum by a microscope were observed.TUNEL assay revealed that the apoptotic cells were increased in LGA and HGA groups.The transcript of caspase-3 was up-regulated to 2.5 fold,accompanied by the up-regulation of caspase-9,Bax and down-regulation of Bcl-2.The protein levels ofprocaspase-3 and the active fraction were up-regulated in LGA and HGA groups.The rat model for GA Ⅰ showed mitochondrial apoptotic pathway may be involved in the GA-induced striatal lesion.Further studies should be taken to investigate the underlying mechanisms.

In previous study, glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro. In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism, 34 male pups were randomly assigned to NS group, low dose GA (LGA, 5 μmol GA/g body weight) group and high dose GA (HGA, 10 μmol GA/g body weight) group. These pups were subcutaneously administered with three injections from postnatal day 3 to 22 at 7:30 am, 15:00 pm and 22:30 pm and killed 12 h after the last injection. Microscopic pathology in corpus striatum was evaluated by HE staining. The apoptotic cells were identified by TUNEL staining. The transcript levels of caspase-3, 8, 9, Bax, Bcl-2 were detected by using real-time PCR and the protein levels of procaspase-3 and the active fraction were evaluated by Western blotting. In LGA and HGA groups, ventricle collapse, cortical atrophy by a macroscope and interstitial edema, vacuolations, widened perivascular space of bilateral striatum by a microscope were observed. TUNEL assay revealed that the apoptotic cells were increased in LGA and HGA groups. The transcript of caspase-3 was up-regulated to 2.5 fold, accompanied by the up-regulation of caspase-9, Bax and down-regulation of Bcl-2. The protein levels of procaspase-3 and the active fraction were up-regulated in LGA and HGA groups. The rat model for GA I showed mitochondrial apoptotic pathway may be involved in the GA-induced striatal lesion. Further studies should be taken to investigate the underlying mechanisms.

Methylmalonic aciduria (MMA) is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase (MCM,mut complementation group) or in the synthesis of the MCM cofactor adenosylcobalamin (cbl complementation groups).The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry (GC-MS),and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions (exon 2-13) and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424A＞G (p.T142A),c.786T＞G (p.S262R),c.808G＞C(p.G270R),c.1323_1324insA,c.1445-1G＞A and c.1676+77A＞C were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682C＞T (p.R228X) and c.323G＞A (p.R108H) were also found in this study.In addition,six previously described single nucleotide polymorphism (SNP),c.636A＞G (p.K212K),c.1495G＞A(p.A499T),c.1595A＞G (p.H532R),c.1992G＞A (p.A664A),c.2011G＞A (p.V671I) and c.1677-53A＞Gwere identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.

Methylmalonic aciduria (MMA) is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase (MCM, mut complementation group) or in the synthesis of the MCM cofactor adenosylcobalamin (cbl complementation groups). The defects in the mut complementation group accounts for the largest number of patients with isolated MMA. At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now. This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients. Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry (GC-MS), and from some of their parents as well. Amplification and direct sequencing of the MUT coding regions (exon 2-13) and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations. In this group, six novel mutations in the MUT gene, c.424A>G (p.T142A), c.786T>G (p.S262R), c.808G>C (p.G270R), c.1323_1324insA, c.1445-1G>A and c.1676+77A>C were identified. p.T142A and p.G270R were respectively detected at a heterozygous level in one patient. Two previously reported mutations, c.682C>T (p.R228X) and c.323G>A (p.R108H) were also found in this study. In addition, six previously described single nucleotide polymorphism (SNP), c.636A>G (p.K212K), c.1495G>A (p.A499T), c.1595A>G (p.H532R), c.1992G>A (p.A664A), c.2011G>A (p.V671I) and c.1677-53A>G were identified. In this study, we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.