Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

ObjectiveTo investigate the clinical efficacy and surgical experience of hermo-expandable metallic prostate stent in the treatment of elderly high-risk BPH patients.MethodsRetrospective analysis was performed on 38 patients with BPH who underwent implantation of hermo-expandable metallic prostate stent from January 2017 to October 2018 in the General Hospital of Eastern Theater Command. The patients were 72 to 89 years old, with preoperative international prostatic symptom score (IPSS) of 25.6±4.1 points, maximum flow rate of urine (MRF) of (4.8±1.2) mL/s, and residual urine volume (RUV) (160.7±70.5) mL. Urinary catheters were placed in 7 patients for 4-8 days due to acute urinary retention.ResultsExcept for the failure in one case, all 37 patients were successfully implanted with the prostate stent at one time, and they urinated immediately after the operation without serious operation-related complications. Follow-up was conducted for 3 months, and the IPSS and RUV of the 37 patients were (15.6±4.3) and (40.7±12.9) mL respectively, which were significantly lower than those before the operation (P<0.05). MRF was (11.1±4.3) mL/s, significantly higher than that before surgery (P<0.05). 22 cases in this group were followed up for 2 years, and their IPSS, MRF and RUV were all stable.ConclusionThe thermo-expandable metallic prostate stent for the treatment of dysuria caused by BPH is effective, reliable and less traumatic. It is a preferred choice for the treatment of the aged BPH patients who are at a high risk and not suitable for surgery.

Objective: To investigate the surgical techniques and clinical effect of Memokath transurethral spiral thermo-expandable prostatic stent (STEPS) implantation in the treatment of BPH. METHODS: From January 2017 to January 2018, 26 BPH patients underwent Memokath transurethral STEPS implantation, 9 under the flexible cystoscope and the other 17 under the rigid cystoscope. The patients were aged 62－91 years old, with a prostate volume of 32－78 ml, postvoid residual urine volume (PVR) of (67.3 ± 11.2) ml, maximum urinary flow rate (Qmax) of (6.3 ± 1.8) ml/s, and IPSS score of 26.7 ± 5.7. Eight of the patients had preoperative urinary retention, of whom, 6 received catheterization and 2 had undergone cystostomy for bladder fistula before STEPS implantation. RESULTS: The operations lasted 15－30 minutes and were successfully completed in 24 cases while stent-shedding occurred in the other 2. Twenty-two of the patients achieved spontaneous urination immediately after surgery and 2 experienced bladder clot embolism. At 3 month after surgery, 24 of the patients showed significant improvement in PVR (［21.4 ± 7.7］ ml), Qmax (［18.3 ± 4.7］ ml/s) and IPSS (8.3 ± 2.1), and 13 exhibited no statistically significant difference from the baseline in the IIEF-5 score (14.1 ± 1.1 vs 14.3 ± 1.0, P > 0.05). At 12 months, all the patients were found with markedly improved urination but no adverse events except recurrent urinary tract infection in 2 cases. CONCLUSIONS Memokath STEPS implantation, with its advantages of simple operation, high safety, definite effectiveness, non-influence on sexual function, is a new effective surgical option for the treatment of BPH.

BACKGROUNDPlasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.

METHODSThe healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.

RESULTSIn this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).

CONCLUSIONSThis study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.

Screening is the bottleneck of directed evolution. In order to address this problem, a series of novel semi-rational designed strategies have been developed based on combinatorial active-site saturation test and iterative saturation mutagenesis, including single code saturation mutagenesis, double code saturation mutagenesis and triple code saturation mutagenesis. By creation of "small and smart" high qualified mutant libraries and combinatorial mutagenesis of specific sites, these new strategies have been successfully applied in multiparameter optimization, e.g. stereo/regioselectivity and activity. This review summarized recent advances in directed evolution and its applications in biocatalysis field.

Background: Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB). Methods: Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis. Results: IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively). Conclusions IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.
Adult ; Alanine Transaminase ; blood ; Antigens, Surface ; Case-Control Studies ; Cytokines ; blood ; DNA, Viral ; Female ; Hepatitis B ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Male ; Young Adult

BACKGROUNDHepatitis B is an immune response-mediated disease. The aim of this study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1 cells and cytokine levels in acute hepatitis B (AHB) patients and chronic hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active phases.

METHODSThirty chronic HBV-infected patients in the immune-tolerant phase (IT group) and 50 chronic hepatitis B patients in the immune-active (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy individuals (HI group) were enrolled in the study. Th cell proportions in peripheral blood, cytokine levels in plasma, and serum levels of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen were detected.

RESULTSThe Th1 cell percentage and Th2/Th1 ratio in the HBV infection group (including IT, IC, and AHB groups) were significantly different from those in HI group (24.10% ± 8.66% and 1.72 ± 0.61 vs. 15.16% ± 4.34% and 2.40 ± 0.74, respectively; all P < 0.001). However, there were no differences in the Th1 cell percentages and Th2/Th1 ratios among the IT, IC, and AHB groups. In HBV infection group, the median levels of Flt3 ligand (Flt3L), interferon (IFN)-γ, and interleukin (IL)-17A were significantly lower than those in HI group (29.26 pg/ml, 33.72 pg/ml, and 12.27 pg/ml vs. 108.54 pg/ml, 66.48 pg/ml, and 35.96 pg/ml, respectively; all P < 0.05). IFN-α2, IL-10, and transforming growth factor (TGF)-β2 median levels in hepatitis group (including patients in AHB and IC groups) were significantly higher than those in IT group (40.14 pg/ml, 13.58 pg/ml, and 557.41 pg/ml vs. 16.74 pg/ml, 6.80 pg/ml, and 419.01 pg/ml, respectively; all P < 0.05), while patients in hepatitis group had significant lower Flt3L level than IT patients (30.77 vs. 59.96 pg/ml, P = 0.021). Compared with IC group, patients in AHB group had significant higher median levels of IL-10, TGF-β1, and TGF-β2 (22.77 pg/ml, 10,447.00 pg/ml, and 782.28 pg/ml vs. 8.66 pg/ml, 3755.50 pg/ml, and 482.87 pg/ml, respectively; all P < 0.05).

CONCLUSIONSCompared with chronic HBV-infected patients in immune-tolerance phase, chronic HBV-infected patients in immune-active phase and AHB patients had similar Th2/Th1 ratios, significantly higher levels of IFN-α2, IL-10, and TGF-β. AHB patients had significantly higher IL-10 and TGF-β levels than chronic HBV-infected patients in immune-active phase.

OBJECTIVETo investigate the clinical features, treatment strategy and risk factors affecting the prognosis of elderly patients with non-small cell lung cancer (NSCLC) complicated by chronic obstructive pulmonary disease (COPD).

METHODSWe retrospectively analyzed the data of elderly patietns (>60 years) with newly diagnosed NSCLC complicated by COPD at the Geriatric Institution of General Hospital of PLA between January, 2000 and June, 2015. The clinical data collected included history of smoking, pulmonary function test results, initial treatments, TNM stage, chief complaints, comorbidities and laboratory tests. The Cox proportional hazards regression model was used to explore the prognostic factors in these patients.

RESULTSA total of 200 NSCLC patients were reviewed, of which 107 (53.5%) patients had the co-morbidity of COPD as confirmed by spirometry using bronchodilator test. The median survival of the patients with NSCLC complicated by COPD was 45.8 months with 1-, 3-, 5-, and 10-year survival rates of 80.4%, 55.4%, 41.0% and 20.0%, respectively. Stratification analysis showed that patients with COPD Gold grades 1 and 2 had a significant longer median overall survival (51.7 and 43.1 months, respectively) than those with grade 3/4 (16.9 months; P=0.020 and 0.043, respectively). Univariate and multivariate analyses using Cox proportional hazards regression model showed that an older age, a higher Gold grade, advanced disease stage (stages III and IV), squamous cell carcinoma, nonsurgical initial treatment, coughing and an elevated serum CEA level were independent risk factors for shorter survival of the patients.

CONCLUSIONMultiple prognostic factors can affect the outcomes of elderly patients with NSCLC complicated by COPD, and a higher COPD Gold grade that fails to respond to treatment within 3 months is the independent risk factor for survival of the patients.

BACKGROUNDHepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a.

METHODSA total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months.

RESULTSBaseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss.

CONCLUSIONSPatients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.

Antiviral Agents ; administration & dosage ; therapeutic use ; Drug Administration Schedule ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B, Chronic ; drug therapy ; metabolism ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Kinetics ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the value of real-time RNA simultaneous amplification and testing (SAT) in the detection of Ureaplasma urealyticum (UU) in the semen of infertile males and its clinical significance. METHODS: We collected semen samples from 542 infertility patients and 120 normal fertile men as controls in the Andrology Clinic of Nanjing General Hospital from March to September 2015. We detected UU infection in the samples using the culture method and SAT technology, respectively. RESULTS: All the UU positive cases (except 4 false positive cases) detected by the culture method were also shown to be positive in SAT. The UU detection rate of SAT was significantly higher than that of the culture method both in the infertility patients (54.1 vs 19.7%, P<0.05) and in the normal controls (42.5 vs 12.5%, P<0.05). CONCLUSIONS SAT is a rapid and accurate method for detecting UU infection in semen samples, with a higher sensitivity and accuracy than the culture method, and it can also be used to evaluate the therapeutic effects. However, the culture method has its own advantages, such as low requirement of technical equipment, easy operation, and possibility of drug sensitivity test at the same time. Therefore, SAT and the culture method can be used alternatively according to the clinical need.
Andrology ; Humans ; Infertility, Male ; microbiology ; Male ; Nucleic Acid Amplification Techniques ; RNA, Bacterial ; analysis ; Semen ; chemistry ; microbiology ; Semen Analysis ; Ureaplasma Infections ; diagnosis ; Ureaplasma urealyticum ; genetics ; isolation & purification