[Analysis of epidemiological characteristics and risk factors of catheter-associated urinary tract infections in patients with perineal and/or hip burns].

Objective: To explore the epidemiological characteristics and risk factors of catheter-associated urinary tract infections in patients with perineal and/or hip burns. Methods: This study was a retrospective case series study. From January 2018 to December 2022, 260 patients with perineal and/or hip burns and urinary catheters indwelling who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of the Second Affiliated Hospital of Zhejiang University School of Medicine, including 192 males and 68 females, aged 20-93 years. The total incidence of catheter-associated urinary tract infections in patients with perineal and/or hip burns, the detection of pathogenic bacteria, and the resistance of major Gram-negative and Gram-positive bacteria to commonly used antimicrobial drugs in clinic were recorded. According to whether catheter-associated urinary tract infection occurred or not, the patients were divided into infection group (43 cases) and non-infection group (217 cases). The basic conditions including gender, age, total burn area, depth of perineal burn, depth of hip burn, and burn site on admission, complications of diabetes mellitus, inhalation injury, and hypoproteinaemia, invasive operations including tracheotomy and non-perineal/hip debridement/skin transplantation surgery, duration of catheter retention, number of urethral catheterization, and bladder irrigation of patients between the two groups were compared, and the independent risk factors influencing the occurrence of catheter-associated urinary tract infections in patients with perineal and/or hip burns were screened. Results: The total incidence of catheter-associated urinary tract infections in patients with perineal and/or hip burns in this study was 16.5% (43/260). The pathogens detected were predominantly Gram-negative, followed by fungi; the main Gram-negative bacterium was Klebsiella pneumoniae, and the main Gram-positive bacterium was Enterococcus faecalis. The resistance rates of Klebsiella pneumoniae to amoxicillin/clavulanic acid, amitraz, amikacin, ciprofloxacin, ceftriaxone, and levofloxacin were higher than 70.0%, the resistance rates of Klebsiella pneumoniae to cefoxitin, cefoperazone/sulbactam, cefepime, meropenem, imipenem, and piperacillin/tazobactam ranged from 56.3% to 68.8%, and the resistance rates of Klebsiella pneumoniae to ceftazidime and tigecycline were lower than 50.0%. The resistance rates of Enterococcus faecalis to ciprofloxacin and penicillin were both 85.7%, the resistance rates of Enterococcus faecalis to erythromycin, clindamycin, moxifloxacin, and tetracycline ranged from 14.3% to 57.1%, and the resistance rates of Enterococcus faecalis to linezolid, tigecycline, and vancomycin were all 0. The differences were statistically significant between the two groups in terms of gender, status of complication of hypoproteinaemia, depth of perineal burn, status of non-perineal/hip debridement/skin transplantation surgery, status of bladder irrigation, number of urethral catheterization, and duration of catheter retention of patients (with χ2 values of 7.80, 4.85, 10.68, 9.11, and 16.48, respectively, and Z values of -4.88 and -5.42, respectively, P<0.05). There were no statistically significant differences in the age, total burn area, complications of diabetes mellitus and inhalation injury, burn site, depth of hip burns, and status of tracheotomy of patients between the two groups (P>0.05). Multifactorial logistic regression analysis showed that gender, deep partial-thickness perineal burns, non-perineal/hip debridement/skin transplantation surgery, bladder irrigation, and duration of catheter retention were the independent risk factors for catheter-associated urinary tract infections in patients with perineal and/or hip burns (with odds ratios of 2.86, 2.63, 2.79, 2.34, and 1.04, respectively, with 95% confidence intervals of 1.21-6.73, 1.03-6.71, 1.03-7.59, 1.05-5.22, and 1.02-1.06, respectively, P<0.05). Conclusions: The incidence of catheter-associated urinary tract infections is high in patients with perineal and/or hip burns, with Klebsiella pneumoniae as the predominant pathogenic bacteria having a high resistance rate to commonly used antimicrobial drugs in clinic. Gender, deep partial-thickness perineal burns, non-perineal/hip debridement/skin transplantation surgery, bladder irrigation, and duration of catheter retention are the independent risk factors for catheter-associated urinary tract infections in patients with perineal and/or hip burns.

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

[Gray zone lymphoma: five cases report and literature review].

Objective: To investigate the clinical and pathological features, treatment, and prognosis of gray zone lymphoma (GZL) . Methods: From July 2, 2013, to February 10, 2021, the clinical and pathological features, treatment, and outcomes of five patients with GZL at the Blood Diseases Hospital, Chinese Academy of Medical Sciences were studied retrospectively. Results: There were one male and 4 females, with a median age of 28 (16-51) years at diagnosis. Four patients had mediastinal (thymic) involvement, two of which had superior vena cava obstruction syndrome, and 3 patients had extra-nodal involvement. There was one case with a limited Ann Arbor stage and 4 cases with a progressive stage. Three patients had cHL-like pathomorphology with scattered Hodgkin-like cells, strongly positive for CD20, positive for CD30, and CD15 was negative; the other two patients had both cHL and DLBCL morphology, with some areas resembling Hodgkin cells and some areas resembling immunoblasts, strongly positive for CD30, and CD15 but negative CD20. Two patients were treated with cHL-like regimens for induction and achieved only partial remission; after salvage therapy with enhanced DLBCL-like regimens, all achieved complete remission (CR) . Three patients were treated with enhanced DLBCL-like immunochemotherapy regimens for induction, and two patients were effective, one of whom achieved CR. Four patients who did not achieve CR were given second or third-line salvage therapy, and all of them recovered. One patient lost parity, one died of disease progression at 35.9 months after diagnosis, and the remaining three maintained sustained remission. Conclusions: GZL is uncommon, usually affects younger patients, is mediastinal and is diagnosed using path morphology and immunophenotype. Patients with newly diagnosed GZL appear to be more sensitive to DLBCL-like immunochemotherapy regimens; relapsed or refractory patients were tended with non-cross-resistant combination chemotherapy or with new drugs.

[Large B-cell lymphoma with IRF4 rearrangement: six case reports and a literature review].

Objective: To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed. Results: ①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity (n=five cases) and no starry sky pattern (n=6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions: LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity's pathogenesis, treatment options, and long-term prognosis still need to be explored further.

[Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis].

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

[Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma].

Objective: The study aims to explore the clinical and biological characteristics of patients with non-IgM lymphoplasmacytic lymphoma (LPL) . Methods: The clinical data of 340 patients with LPL admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were collected retrospectively, including 23 cases of the non-IgM LPL and 317 cases of the Waldenström's macroglobulinemia (WM) , from July 1993 to August 2020. The clinical and biological characteristics of the two groups were compared. Results: Among 23 patients with the non-IgM type LPL, two patients secreted monoclonal IgA, 14 patients secreted monoclonal IgG, and seven patients did not secrete monoclonal immunoglobulin. The median age of the non-IgM LPL and WM were both 62 (35-81) years old. Compared with the WM group, the proportion of women (56.5% vs 27.3%, P=0.007) , the proportion of splenomegaly (60.1% vs 43.8%, P=0.100) , and the proportion of extranodal invasion (21.7% vs 12.3%, P=0.672) in non-IgM LPL group were higher. Eighteen patients were tested for MYD88 gene mutation, and the overall mutation rate of MYD88 was 55.6%. In the non-IgM LPL group, a total of 17 patients received treatment, which had a comparable proportion (94.4% vs 92.7%, P=0.488) to the WM group. Sixteen patients were evaluated for efficacy, and the overall remission rate of the first-line treatment was 87.5%. The median follow-up time was 33.9 (3.5-125.1) months, and the median PFS and OS were both not reached. The 3-year PFS and OS rates were 71.4% and 68.9%, respectively. In the WM group, the median PFS was 66.2 months and the median OS was 78.1 months. Compared with the WM group, in the non-IgM group no significant differences in PFS (P=0.340) and OS (P=0.544) were seen. Conclusion: The clinical and biological characteristics of the non-IgM LPL and WM patients were similar. However, the proportion of women and extranodal involvement were higher in the non-IgM LPL group. The survival and prognosis of the non-IgM LPL patients were similar to those of the WM patients.

[Clinical analysis of fludarabine and cyclophosphamide combined with rituximab in the first-line treatment of 43 cases of chronic lymphoblastic leukemia].

Objective: To investigate the efficacy of fludarabine and cyclophosphamide combined with rituximab (FCR) in previously untreated patients with chronic lymphocytic leukemia (CLL) . Methods: The clinical data of 43 enrolled patients from May 2004 to December 2017 were analyzed the efficacy and survival results. Results: A total of 43 patients with 31 males and 12 females, and the median age was 58 years old (range 36 to72) before treatment. There were 8 patients with symptom B. The median number of peripheral blood lymphocyte was 26 (3-550) ×10(9)/L. IGHV unmutated was detected in 62.1% (18/29) patients, P53 deletion in 14% (6/43) patients, RB1 deletion in 18.6% (8/43) patients, Trisomy 12 in 25.6% (11/33) patients, ATM deletion in 16.7% (7/42) patients, respectively. The median number of treatment courses administered was 4 (range 2-6) . Twenty patients obtained CR (46.5%) , 18 patients obtained PR, 4 patients were SD, 1 patient was PD. The overall response rate (ORR) was 88.37%. Seven patients obtained MRD negative. After the median follow-up time of 51 (6-167) months, median PFS was 67 (29-105) months, median OS was not reach, 5-year PFS was (62.1±8.6) %, 10-year PFS was (31±14.3) %, 5-year OS was (70.5±8.3) %, and 10-year OS was (51.3±13.8) %. Less than 4 courses predicted adverse OS (P<0.05) . P53 deletion and less than 4 courses were associated with poor PFS (P<0.001) , and the prognostic value still remained after multivariate analysis[HR=7.65 (95%CI 1.74-33.60) , P=0.007; HR=3.75 (95%CI 1.19-11.80) , P=0.025]. Eighteen patients (41.9%) appeared grade 2-3 infection after chemotherapy, and 19 patients (44.2%) appeared grade 3-4 hematological adverse reactions. One patient (2.3%) was developed tumor lysis syndrome. All adverse reactions were controlled or recovered spontaneously. Conclusion: Previously untreated CLL patients treated with FCR had a high response rate and good survival rate, which is an important treatment choice for fit patients.

[The prognostic significance of POD24 in 106 cases with splenic marginal lymphoma with bone marrow invasion].

Objective: To explore the effect of progression of disease within 24 months (POD24) on overall survival (OS) of splenic marginal lymphoma (SMZL) with bone marrow invasion, and to compare the clinical characteristics between POD24 SMZL with non-POD24 SMZL patients. Methods: The SMZL patients with bone marrow invasions were retrospectively analyzed between January 2002 and January 2017 treated in our institute, and the patients with sufficient follow-up time to judge POD24 were evaluated the clinical characteristics and prognosis, patients who died of non-progressive factors were excluded. Results: 106 patients were enrolled with a median age of 57 (25-79) years old. ①Clinical characteristics: All patients presented with bone marrow invasion and splenomegaly, 59.4% (63/106) with huge spleen, 14.8% (15/101) with hepatomegaly. Complex karyotype were found in 22.7% (18/79) patients; 13q deletion, 11q (ATM) deletion, 17p (TP53) deletion, and CEP12 abnormality patients presented with the percentage of 5.1% (4/78) , 1.3% (1/72) , 2.5% (2/80) , and 7.5% (4/53) , respectively.②Survival analysis: Univariate analysis showed that POD24, HGB less than 100 g/L and FISH detection of trisomy 12 were poor prognostic factors of OS. Multivariate analysis showed that only POD24 had independent prognostic significance[HR=20.116 (95%CI 2.226-181.820) , P=0.008]. ③Subgroup features: Patients with POD24 had significantly higher rates of mediastinal lymphadenopathy (63.6%vs 18.9%, P=0.005) and complex karyotype (50.0%vs 17.9%, P=0.024) than those without POD24. While the incidence of abdominal lymphadenopathy, anemia, thrombocytopenia, the lower albumin, and the increasing lactate dehydrogenase were higher in POD24 patients, but with no statistically difference. Conclusion: POD24 is an independent prognostic factor of the OS in SMZL. SMZL patients with mediastinal lymphadenopathy and complex karyotypes when diagnosed have a higher risk of POD24.

[Clinical analysis of 24 patients of hairy cell leukemia treated by cladribine].

Objective: To investigate the curative effect of hairy cell leukemia by clatabine. Methods: The clinical data of 24 patients with hairy cell leukemia treated by cladribine from November 2006 to October 2017 were analyzed retrospectively, then the curative effect and adverse drug reaction were analyzed. Results: ① A total of 24 patients including 22 male and 2 female, and the median age was 49.5 years (range 33 to 76) at diagnosis. There were 20 patients with of splenomegaly (4 patients with mild splenomegaly, 4 moderate splenomegaly, and 12 massive splenomegaly), 3 patients with enlargement of lymph nodes, and 1 patients who had undergone splenectomy. Five patients were pancytopenia, 15 were cytopenia in 2 lineages, and 4 patients were cytopenia only in one lineage. The median ratio of HCL cells detected by flow cytometry in bone marrow was 21.79% (0.69%-68.96%). BRAF mutation was detected in 15 patients by first generation or next generation sequencing technology. ② Among 24 patients, 20 were treated with cladribine alone (one course in 19 patients, 2 courses in 1 patient), and 4 patients were treated with cladribine combined with rituximab (one course in 3 patients, 2 courses in 1 patient). Excepting 5 patients whose follow-up time was not reaching 6 months, 19 patients were evaluated for efficacy in 6-12 months after treatment: 9 patients obtained CR, 9 obtained unconfirmed CR (Cru), the other 1 obtained PR, the CR/CRu rate was 94.7%, the overall response rate (ORR) was 100.0%. ③ All the 24 patients appeared 2-4 grade hematological adverse reactions after cladribine treatment, which were mainly grade 3/4 neutropenia (66.67%) and grade 3/4 thrombocytopenia (29.2%). All the adverse reactions were controlled or recovered spontaneously. ④ After the median follow-up time of 15 (3-133) months, no progression, recurrence or death occurred in the patients. Both median OS and PFS were not reached. Conclusion: This study suggests that treatment of HCL with cladribine has high response rate, controllable adverse reactions and the good prognosis.

[Role of minimal residual disease detection by multiparameter flow cytometry in newly diagnosed multiple myeloma: an analysis of 106 patients].

Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62.2% vs 36.2%, χ(2)=6.536, P=0.011). ② Of 48 patients in complete remission (CR), 7 (14.6%) was MRD positive, 5 of them showed disease progression (PD) during the follow-up, and 3 died. The median progression free survival (PFS) was 19 months, and the median overall survival (OS) was 28 months, both were significantly shorter than the CR patients with MRD-negative (P<0.05). ③At a median follow-up of 38 months, MRD-negative patients showed significantly superior outcomes compared with MRD positive ones, the PFS was not reach versus 17 months and the OS was not reach for both (P<0.001). Patients were grouped into 4 categories according to their MRD levels: 1% or higher, 0.1% to less than 1%, 0.01% to less than 0.1%, or negative. It showed that the outcomes (PFS and OS) tended to be improved along with the tumor depletion. ④ Multivariate prognostic analysis showed that MRD was a powerful independent prognostic factor for PFS[HR=0.133 (95% CI 0.062-0.288) , P<0.001] and OS[HR=0.156 (95% CI 0.050-0.484) , P=0.001]. According to MRD and cytogenetics, the patients were classified into 4 groups. High risk patients with MRD negative presented a significantly better outcome than high risk patients with MRD-positive, and a similar one to the standard risk patients with MRD-negative. Conclusions: MRD negativity by MFC was more popular in MM patients undergoing ASCT. MRD was an independent prognostic factor in MM. And the prognosis of MM patients can be stratified according to the level of MRD. MRD-negative patients with high risk cytogenetics presented a similar outcome to the standard risk ones. MRD by MFC should therefore be considered more widely applied in the clinic.

[Clinical analysis of 70 chronic lymphocytic leukemia patients with trisomy 12 detected by FISH].

Objective: To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12). Methods: Clinical data of 330 CLL patients were analyzed retrospectively by using FISH (CEP12) to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients (70 cases) were compared with those CEP12 negative patients (260 cases). Results: Compared with CEP12 negative CLL patients, the proportion of hepatomegaly (13.6% vs 4.0%, P=0.011) and LDH>247 U/L (43.3% vs 18.5%, χ(2)=15.892, P<0.001) in CEP12 positive CLL patients were much higher, respectively. There were no significant differences between age, sex, clinical stage, ß(2)-microglobulin level, IGHV mutation ratio and splenomegaly/lymphadenopathy in these two subgroups. However, compared with CEP12 negative patients, CEP12 positive patients had higher ratio of FMC7 (23.8% vs 12.7%, χ(2)=4.730, P=0.030), and lower ratio of CD23 (95.2% vs 99.6%, P=0.033). The overall response rates (ORR) in Fludarabine (without Rituximab), Rituximab (with or without Fludarabine) and the traditional chemotherapy group (chlorambucil, CHOP or CHOP-like) were 77.5% (31/40), 84.8% (56/66) and 45.4% (50/110), respectively. The ORR of the traditional chemotherapy group was lower than that of the Fludarabine group and Rituximab group. For CEP12 positive patients, the ORR was inferior to CEP12 negative patients when only using Fludarabine (P<0.05). However, when using Rituximab, the difference could be eliminated, and the ORR was even a little higher in CEP12 negative patients (91.7% vs 81.0%, P=0.306). Compared with CEP12 negative patients, there were no significant differences in progression-free survival (PFS) (χ(2)=0.410, P=0.478) and overall survival (OS) (χ(2)=0.052, P=0.180) for CEP12 positive patients whom the median time from diagnosis to start treatment and OS time was 22.6 (95%CI 15.4-31.7) and 118.5 (95%CI 74.5-162.4) month while the 5-year PFS and OS were (52.9±7.6)% and (74.8±6.6)%. Conclusions: CEP12 positive CLL patients are more common in hepatomegaly and higher level of LDH. The traditional chemotherapy treatment had the lowest efficacy, and the curative effect of single use of fludarabine is not as good as that of CEP12 negative patients, however, when using Ritaximab, the efficacy could be comparable.

[Long-term follow-up of multiple myeloma after autologous hematopoietic stem cell transplantation: a single center results].

Objective: To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma (MM) , including induction therapy, autologous hematopoietic stem cell transplantation (ASCT) and consolidation and maintenance therapy. Methods: Clinical records of 144 patients with MM from January 1, 2005 to February 1, 2016 were retrospectively analyzed. Results: The overall response rate (ORR) after ASCT was 100.0%, in which the complete remission (CR) was 64.1% and the best treatment response rate of superior to PR was 89.4%. During a median follow-up of 47 months, patients with an overall survival (OS) and progression free survival (PFS) was 120.9 and 56.9 months respectively. 5y-OS (73.7±4.7) %, 7y-OS (60.5±6.3) %; 3y-PFS (69.2±4.2) %, 5y-PFS (47.8±5.3) %. The median OS and PFS between the first line transplantation group and salvage transplantation group were 120.9 months vs 50.1 months and 60.2 months vs 16.7 months (all P=0.000). In 127 patients with R-ISS staging, the median survival of Ⅰ, Ⅱ, Ⅲ stage was 120.9 months (n=43) , 88.4 months (n=64) , 35.6 months (n=20) , respectively (P=0.000). For subgroup analysis of survival in early and late ASCT, the median OS of patients with R-ISS stage Ⅲ (35.6 months vs 15.8 months, P=0.031) and the median PFS of two groups (phase Ⅰ: 72.1 months vs 18.9 months, P=0.000; Ⅱ: 53.4 months vs 16.7 months, P=0.012; Ⅲ: 28.5 months vs 5.9 months, P=0.001) were different. Multivariate analysis showed that only R-ISS and the degree of remission before transplantation had impact on OS (HR=8.486, 95% CI 2.549-28.255, P=0.003) and PFS (HR=2.412, 95% CI 1.364-4.266, P=0.002) , respectively. Conclusion: The combined protocol containing ASCT is effective for MM patients, improving remission rate and remission depth, prolonging PFS and OS. First line transplantation could significantly prolong the OS and PFS as compared with salvage transplantation. R-ISS and pre-transplantation remission depth are prognostic factors for survival.

[Clinical and bacteriological analysis of lymphoid tissue neoplasms patients with bacteria bloodstream infections].

Objective: To investigate the clinical status of lymphoid tissue neoplasms patients with bacteria bloodstream infections, bacteriology and drug susceptibility results, and provide the basis for rational clinical anti-infection option. Methods: A retrospectively analysis of clinical data and bacterial susceptibility test results of patients with bacteria bloodstream infections from September 2010 to December 2014 was conducted. Results: A total of 134 cases including 107 patients with bloodstream infections were enrolled. 84 cases were male, 50 cases were female, the median age was 31 (12-71) years old. 112 cases were agranulocytosis, and 106 cases were severe agranulocytosis (ANC<0.1×10(9)/L) . 27 cases underwent hematopoietic stem cell transplantation, 100 cases received chemotherapy[33 cases with VD (I) CP±L (vincristine+daunorubicin/idarubicin + cyclophosphamide + prednison±asparaginasum) induction chemotherapy, 41 cases with intensive chemotherapy of Hyper-CVAD/MA or MA (mitoxantrone+cytarabine) , 26 cases with other chemotherapy regimens], and 7 cases were infected without chemotherapy. 10 patients discharged from hospital owing to treatment abandoning, 120 cases were cured through anti-infective therapy, 2 patients died of bacteria bloodstream infections, 1 patient died of sudden cardiac, and 1 patient died of GVHD after allogenic hematopoietic stem cell transplantation. A total of 144 strains were isolated, including 108 strains (75.0%) of Gram-negative bacteria and 36 strains (25.0%) of Gram-positive cocci. The susceptibility of Gram-negative bacteria to the carbapenems was 98.00%, and the adjustment treatment rate of carbapenems was 3.0%. The susceptibility of Gram-negative bacteria to the other antibiotics was 60.30%, and the adjustment treatment rate was 90.5%. The susceptibility of Grampositive cocci to the carbapenems was 49.3%, and to glycopeptides and linezolid was 100.0%. Comparing all patients'empirical use of antimicrobial agents with the drugs susceptibility results of blood cultures, 80.1% of the patients'initial drug selection was sensitive. Conclusion: The lymphoid neoplasms patients experienced bacteria bloodstream infections most often after receiving the chemotherapy regimens of treating acute lymphoblastic leukemia. The majority type of bacteria was Gram-negative bacteria. Drug susceptibility test showed that susceptibility of Gram-negative bacteria to the carbapenems was the highest, and the treatment adjustment rate was obviously lower. The susceptibility of Gram-positive cocci to glycopeptides and linezolid was high, and which could be applied to the patients with Gram-positive cocci sepsis on basis of susceptibility results in general.

[IGHV mutational statue in patients with splenic marginal zone lymphoma].

Objective: To investigate the IGHV mutational status and its differences from Caucasian in splenic marginal zone lymphoma (SMZL). Methods: A retrospective study on 40 SMZL cases were performed to detect the V-D-J sequence of IGHV by plasmid cloning sequencing, comparing the data with the most homologous germ line V sequence in database, identifying the stereotype of patients through cluster analysis and alignment. The clinical and laboratory characteristics were compared between the patients with IGHV mutation and without mutations. Results: In SMZL patients, the proportion of IGHV mutations was 75%, consistent with data from Caucasian. In V region, the usage of V3-23 subtype was lower in Chinese patients compared with Caucasian (2.6% vs 18.0%, P=0.006), whereas the V2-70 subtype was used with high proportion (10.3% vs 0.8%, P=0.002). In D region, the D2-21 and D6-13 gene were used frequently (17.9% vs 2.3%, P<0.001; 12.8% vs 3.8%, P=0.046). One new stereotype was found, and the SMZL-biased V1-2 gene was mostly used (25.6%). The levels of IgG and IgA were significantly increased in IGHV without mutations as compared with mutations [10.70 (5.28-15.50) g/L vs 12.90 (7.71-23.50) g/L, 1.06 (0.21-3.13) g/L vs 1.66 (0.81-2.93) g/L, P=0.038, 0.040]. The only two 17p deletion patients were IGHV without mutaions. The progression free survival (PFS) was significantly prolonged in IGHV mutations (P=0.009), and there was no significant difference regarding to the overall survival between the two subgroups (P=0.430). Conclusion: The proportion of IGHV mutaions was similar to the data in Caucasian. There was disparity in the usage of V and D regions between Chinese and Caucasian, and the SMZL-biased V1-2 gene were used more frequently in Chinese patients. One new stereotype was identified. In the IGHV without mutations group, the levels of IgG and IgA were significantly increased.

Phoenixin: A candidate pruritogen in the mouse.

Phoenixin (PNX) is a 14-amino acid amidated peptide (PNX-14) or an N-terminal extended 20-residue amidated peptide (PNX-20) recently identified in neural and non-neural tissue. Mass spectrometry analysis identified a major peak corresponding to PNX-14, with negligible PNX-20, in mouse spinal cord extracts. Using a previously characterized antiserum that recognized both PNX-14 and PNX-20, PNX-immunoreactivity (irPNX) was detected in a population of dorsal root ganglion (DRG) cells and in cell processes densely distributed to the superficial layers of the dorsal horn; irPNX cell processes were also detected in the skin. The retrograde tracer, Fluorogold, injected subcutaneously (s.c.) to the back of the cervical and thoracic spinal cord of mice, labeled a population of DRG, some of which were also irPNX. PNX-14 (2, 4 and 8 mg/kg) injected s.c.to the nape of the neck provoked dose-dependent repetitive scratching bouts directed to the back of the neck with the hindpaws. The number of scratching bouts varied from 16 to 95 in 30 min, commencing within 5 min post-injection and lasted 10-15 min. Pretreatment of mice at -20 min with nalfurafine (20 µg/kg, s.c.), the kappa opioid receptor agonist, significantly reduced the number of bouts induced by PNX-14 (4 mg/kg) compared with that of saline-pretreated mice. Our results suggest that the peptide, PNX-14, serves as one of the endogenous signal molecules transducing itch sensation in the mouse.

Phoenixin: a novel peptide in rodent sensory ganglia.

Phoenixin-14 amide, herein referred to as phoenixin, is a newly identified peptide from the rat brain. Using a previously characterized rabbit polyclonal antiserum against phoenixin, enzyme-immunoassay detected a high level (>4.5 ng/g tissue) of phoenixin-immunoreactivity (irPNX) in the rat spinal cords. Immunohistochemical studies revealed irPNX in networks of cell processes in the superficial dorsal horn, spinal trigeminal tract and nucleus of the solitary tract; and in a population of dorsal root, trigeminal and nodose ganglion cells. The pattern of distribution of irPNX in the superficial layers of the dorsal horn was similar to that of substance P immunoreactivity (irSP). Double-labeling the dorsal root ganglion sections showed that irPNX and irSP express in different populations of ganglion cells. In awake mice, intrathecal injection of phoenixin (1 or 5 µg) did not significantly affect the tail-flick latency as compared to that in animals injected with artificial cerebrospinal fluid (aCSF). Intrathecal administration of phoenixin (0.5, 1.25 or 2.5 µg) significantly reduced the number of writhes elicited by intraperitoneal injection of acetic acid (0.6%, 0.3 ml/30 g) as compared to that in mice injected with aCSF. While not affecting the tail-flick latency, phoenixin antiserum (1:100) injected intrathecally 10 min prior to the intraperitoneal injection of acetic acid significantly increased the number of writhes as compared to mice pre-treated with normal rabbit serum. Intrathecal injection of non-amidated phoenixin (2.5 µg) did not significantly alter the number of writhes evoked by acetic acid. Our result shows that phoenixin is expressed in sensory neurons of the dorsal root, nodose and trigeminal ganglia, the amidated peptide is bioactive, and exogenously administered phoenixin may preferentially suppress visceral as opposed to thermal pain.