BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

Monoclonal gammopathy of neural significance (MGNS) belongs to the category of monoclonal gammopathy of clinically significance. It is an early-stage disease that mainly occurs in peripheral nerves and is not sufficient for the diagnosis of multiple myeloma or lymphoma. MGNS needs to be differentiated from neuropathies due to POEMS syndrome and light-chain amyloidosis; if necessary, nerve biopsy can be performed to clarify the relationship between peripheral nerve symptoms and lymphoplasmacytic disease. Treatment of MGNS is recommended to give intravenous gammaglobulin, plasma exchange and targeted anti-lymphoplasmacytic tumour therapy such as CD20 monoclonal antibody. Early recognition and intervention of MGNS, with multidisciplinary cooperation, will help to reduce the risk of malignancy and the incidence of disability.

Plasma cell disorders are a group of heterogeneous diseases originating from plasma cells, including multiple myeloma, plasma cell leukemia and light-chain amyloidosis, etc. Monoclonal plasma cells are detected in bone marrow and affected tissues, monoclonal immunoglobulin or components are detected in serum or urine, and some end-organs are injured. Plasma cell disorders accompanied by t(11;14) have unique biological characteristics and unsatisfactory response to proteasome inhibitors. With t(11;14) translocation, the expressions of cyclin D1 and anti-apoptotic protein bcl-2 are relatively high, which lead to the occurrence of plasma cell disorders and have implications for the prognosis of disease. Venetoclax is a bcl-2 inhibitor, and its single agent or combined with other drugs has achieved good efficacy in treatment of plasma cell disorders with t(11;14). This article reviews the progress of bcl-2 inhibitors in treatment of plasma cell disorders.

Objective:To investigate the expression of serum human phosphatidylethanolamine-binding protein 4 (hPEBP4) in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 59 symptomatic MM patients admitted to West Branch of Beijing Chaoyang Hospital from September 2016 to September 2018 were selected as the research objects. According to the CRAB symptoms [elevated serum calcium (C), kidney injury (R), anemia (A), bone lesions (B)], all patients were divided into 2 groups, including the active group of 44 patients with CRAB symptoms, and the response group of 15 patients who achieved at least partial remission after chemotherapy and symptom relief of CRAB. According to the degree of bone lesions (BL), 30 patients with severe bone-related events were grouped as the severe bone lesions (SBL) group, and 14 patients were grouped as the non-severe bone lesions (NSBL) group. According to the revised international prognostic staging system (R-ISS), patients in the active group were divided into three subgroups: stage Ⅰ, stage Ⅱ, and stage Ⅲ, including 26, 11 and 7 patients, respectively. A total of 15 healthy examination people whose gender and age matched those of the patients were treated as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of hPEBP4, tumor necrosis factor ligand superfamily member 14 (LIGHT/TNFSF14) and activin A of patients in different groups. Pearson was used to analyze the relationship of the expressions of multiple factors in the active group. The optimal cut-off value of multiple factors diagnosing MM was determined by using receiver operating characteristic (ROC) curve, and according to the cut-off value, the differences in overall survival (OS) of patients with different stratification were compared.Results:In the active group, the respond group, the healthy control group, the level of hPEBP4 was (1.48±0.64) μg/L, (1.49±0.75) μg/L, (0.31±0.10) μg/L, respectively; the level of LIGHT/TNFSF14 was (169±112) ng/L, (256±132) ng/L, (44±27) ng/L,respectively; the level of activin A was (383±266) ng/L, (223±79) ng/L, (234±85) ng/L, respectively; and the differences were statistically significant (all P<0.05). In the active group, the level of hPEBP4 was (1.06±0.60) μg/L, (1.15±0.50) μg/L, (1.73±0.68) μg/L, respectively in patients with stage R-ISSⅠ, R-ISSⅡ and R-ISS Ⅲ, and the difference was statistically significant ( F=3.287, P=0.032). The level of activin A was (219±55) ng/L, (247±117) ng/L, (450±215) ng/L, respectively among patients in stage R-ISSⅠ, R-ISSⅡ, R-ISS Ⅲ, and the level of activin A in stage R-ISS Ⅲ was higher than that in stage R-ISSⅠand R-ISSⅡ (all P < 0.05). The levels of LIGHT/TNFSF14 and activin A of SBL patients were higher than those of NSBL patients [(174±101) ng/L vs. (98±53) ng/L; (467±238) ng/L vs. (189±71) ng/L, all P < 0.05]. The level of hPEBP4 was positively correlated with the levels of M protein ( r=0.694, P < 0.01) and activin A ( r=0.252, P < 0.01) of IgG patients in the active group. ROC curve analysis showed that the optimal cut-off value of hPEBP4, LIGHT/TNFSF14, activin A diagnosing MM was 1.04 μg/L, 97.0 μg/L, 156.2 ng/L. The median overall survival (OS) time of patients with hPEBP4 >1.04 μg/L and hPEBP4 ≤ 1.04 μg/L was 57 months (95% CI 22-92 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05); while the median OS time of patients with activin A ≥ 156.2 ng/L and activin A < 156.2 ng/L was 61 months (95% CI 24-98 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05). Conclusions:High expression level of hPEBP4 is related with the progression of MM. It is positively related with the level of M protein and negatively with the OS of MM patients. It is suggested that hPEBP4 may be used as an important marker to judge disease progression and tumor burden in MM. LIGHT/TNFSF14 and activin A cooperate with hPEBP4 to participate in the pathological processes of tumor microenvironment of MM.

Objective:To explore the accuracy of determination of the pathogen in children with lower respiratory infection according to sputum properties and the selection of corresponding antibiotics.To analyze the relationship between children's age, length of hospital stays and sputum culture positive rate.Methods:From March 2015 to November 2016, 300 children with lower respiratory infection in the Seventh Affiliated Hospital of Guangxi Medical University were selected.The isolated sputums through the nasal cavity were cultured, the sputum properties and antibiotics used at the beginning and 3-4 days later(after sputum culture) were recorded.Results:The sputum culture showed that 110 of 300 cases with lower respiratory infection were positive.Main pathogens were streptococcus pneumoniae, E.coli, staphylococcus aureus, klebsiella pneumoniae subspecies.Compared with the children with positive sputum culture, for white phlegm sputum and yellow phlegm sputum, the children with sputum culture negative had higher accuracy of antibiotic use(white phlegm sputum: 64.4%, yellow phlegm sputum: 57.1%), the difference was statistically significant (χ 2=36.04, P<0.01). The bacteria positive rate and multiple resistance rate had no statistically significant differences in length of treatment time prior to admission(all P>0.05). However, the bacteria positive rate (hospital stay ≤7 d: 24.7%, hospital stay>7 d: 48.1%, χ 2=17.66) and multiple resistance rate (hospital stay≤7 d: 13.9%, hospital stay>7 d: 35.1%; χ 2=5.40) had statistically significant differences in the length of hospitalization(all P<0.05). The bacteria positive rates in different age groups were as follows: 1-6 months: 48.1%, >6-36 months: 28.3%, >36 months: 25.0%.Compared with the two others, the positive rate of 1-6 months was higher and had statistically significant difference (χ 2=13.64, P<0.05). Conclusion:Accuracy of antibiotics use has a certain relationship with sputum color or properties and the result of sputum culture, for white phlegm sputum and yellow phlegm sputum, the accuracy of antibiotics use is higher.Once identified pathogen, sensitive antibiotics should be adopted.Probably, bacteria positive rate and multiple resistance rate have a certain relationship with the length of hospital stay and age.

A 49-year-old woman was admitted to hospital with intermittent dizziness and fatigue for 7 years. The symptoms were aggravated and accompanied by bone pain for more than 4 months. She was referred to our hospital. Laboratory tests and imaging findings suggested that acquired Fanconi Syndrome (FS) was associated with smoldering multiple myeloma (MM). Renal biopsy and electron microscopy confirmed the diagnosis of proximal light chain tubular disease (LCPT). LCPT causes proximal tubular dysfunction, which is characterized by the cytoplasmic crystal deposition usually kappa monoclonal light chain in the proximal tubule. MM with FS and LCPT is less common in clinical practice because it is difficult to diagnose. This is a typical case focusing on the differential diagnosis of monoclonal gammopathy of renal significance(MGRS) such as LCPT and plasma cells diseases.

Light chain amyloidosis (AL) is a clonal plasma cell disease in which multiple organs of human body are damaged by amyloid misfolded by light chain of immunoglobulin. Its mechanism is still unclear. Clinically, heart failure, renal insufficiency and other organs failure are seen as prominent symptoms for the majority of patients. The main treatments include melphalan combined with dexamethasone or bortezomib or other target new drugs or autologous stem cell transplantation. Efficacy assessment depends on not only the serum free light chain and M protein levels to judge the hematological response, but also pro-brain natriuretic peptide and troponin I as biomarker to assess the heart and other vital organs function for better outcomes. In the era of new drugs, cardiac involvement is a determinant of survival and prognosis of AL patients. The modern AL treatment usually takes new drug targeted therapy against plasma cells, and combines with anti-amyloidosis treatment to clear the accumulation of amyloidosis chaperonin. Despite the promising advances in treatment, many problems need to be resolved.

Plasma cell leukemia (PCL) is a rare and aggressive malignant plasma cell tumor that is clinically susceptible to extramedullary lesions. It is classified into two types: primary PCL (pPCL) and secondary PCL (sPCL), of which 60 % are pPCL. The treatment of new drugs such as bortezomib and lenalidomide is important for improving the overall survival and disease-free survival of PCL, especially after induction of bortezomib-based chemotherapy,combined with autologous hematopoietic stem cell transplantation (auto-HSCT) can improve the survival of patients. Whether to adopt the next step of allogeneic hematopoietic stem cell transplantation (allo-HSCT) still needs further investigation. For young and suitable patients, early new drug-based regimen chemotherapy combined with auto-HSCT can be used, and if a suitable donor is available, the further allo-HSCT consolidation therapy is feasible. For elderly patients (≥65 years old), a new drug-based regimen can be used to induce chemotherapy, and further followed consolidation therapy plus maintenance therapy. Whether to take auto-HSCT after early induction chemotherapy depends on the individualized factors of the patient. The next generation anti-plasma cells drugs, monoclonal antibodies and other immunotherapies or new drugs in clinical trials are also worth exploring.

Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309

Objective Toexplore the application value of diffusion tensor imaging (DTI) in evaluating evaluation offunctional changes of the in patients with primary trigeminal neuralgia caused (PTN) by neurovascular compression. Methods 40 unilateral PTN patients and 40 healthy volunteers were enrolled in ourstudy.They allAll patients underwent the general sequences and DTI ,and then to measured the ADC and FA values of the trigeminal nerves. Results (1) Compared with contralateral side (0.408 ± 0.054)and bilateral sides in control group(0.423 ± 0.057), FA value of the ipsilateral side in PTN group(0.330 ± 0.056) was significant lower (P< 0.05)compared with the contralateral side (0.408 ± 0.054) and bilateral sides in control group (0.423 ± 0.057).The ADC value of ipsilateralside (2.052 ± 0.473)× 10-3 mm2/s was significantly higher (P < 0.05) thancompared withthe contralateral side (1.541 ± 0.266) ×10-3 mm2/s and bilateral sides in control group(1.431 ± 0.308) ×10-3 mm2/s. (2) An There's a nnegative correlation was found (r = -0.613,P < 0.001) between the loss of FA and the increase of ADC (r = -0.613,P < 0.001). Conclusion DTI could be used to evaluate the changes of neuratrophy and demyelination ,so it canmight be used of in diagnosis and treatment of PTNin further way.