Drug resistance and genomic characteristics of Salmonella enterica serovar London from clinical and food sources in Hangzhou City from 2017 to 2021 / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.

Comparative analysis on occupational hazards of three welding operations / 中华劳动卫生职业病杂志

Objective: To explore the occupational hazards caused by three kinds of welding operations, and to provide data support for individual protection. Methods: In October 2020, the welding fumes, metal elements and welding arc generated by three welding operations of argon gas shielded welding (JS80 welding wire) , manual welding (ZS60A welding rod) and carbon dioxide shielded welding (907A flux cored wire) were collected and measured in the welding laboratory. The samples were analyze and compare in the laboratory, and the differences of the occupational hazard factors of the three welding operations were judged. Results: The concentration of welding fume produced by carbon dioxide shielded welding, manual welding (ZS60A electrode) , and argon gas shielded welding (JS80 welding wires) were 6.80 mg/m(3), 6.17 mg/m(3), and 3.13 mg/m(3), respectively. The effective irradiance of the welding arc outside the welding mask from high to low is manual welding (ZS60A electrode) , carbon dioxide shielded welding (907A flux-cored welding wire) , and argon shielded welding (JS80 welding wire) , respectively 1 010.7, 740.9, 589.5 μW/cm(2). The long-wave ultraviolet UVA intensity generated by argon shielded welding (JS80 welding wire) is the largest, which is 1 500 μW/cm(2). The content of Mn in the three welding operations is the highest, and JS80 welding wire has the highest Mn content of 128493.2 mg/kg. 907A flux cored wire has the highest Ti content, which is 24355.5mg/kg. The electrode ZS60A has the highest Cu content, which is 24422.12 mg/kg. Conclusion: The intensity of occupational hazards is different in the three kinds of welding operations, so the methods of personal protective equipment, field exposure assessment and health monitoring should be more targeted.

The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching / 中华外科杂志

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

SET8 Inhibition Potentiates Radiotherapy by Suppressing DNA Damage Repair in Carcinomas / 生物医学与环境科学（英文）

Objective@#SET8 is a member of the SET domain-containing family and the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20me1). SET8 has been implicated in many essential cellular processes, including cell cycle regulation, DNA replication, DNA damage response, and carcinogenesis. There is no conclusive evidence, however, regarding the effect of SET8 on radiotherapy. In the current study we determined the efficacy of SET8 inhibition on radiotherapy of tumors and the underlying mechanism.@*Methods@#First, we explored the radiotherapy benefit of the SET8 expression signature by analyzing clinical data. Then, we measured a series of biological endpoints, including the xenograft tumor growth in mice and apoptosis, frequency of micronuclei, and foci of 53BP1 and γ-H2AX in cells to detect the SET8 effects on radiosensitivity. RNA sequencing and subsequent experiments were exploited to verify the mechanism underlying the SET8 effects on radiotherapy.@*Results@#Low expression of SET8 predicted a better benefit to radiotherapy in lung adenocarcinoma (LUAD) and invasive breast carcinoma (BRCA) patients. Furthermore, genetic deletion of SET8 significantly enhanced radiation treatment efficacy in a murine tumor model, and A549 and MCF7 cells; SET8 overexpression decreased the radiosensitivity. SET8 inhibition induced more apoptosis, the frequency of micronuclei, and blocked the kinetics process of DNA damage repair as 53BP1 and γ-H2AX foci remained in cells. Moreover, RNF8 was positively correlated with the SET8 impact on DNA damage repair.@*Conclusion@#Our results demonstrated that SET8 inhibition enhanced radiosensitivity by suppressing DNA damage repair, thus suggesting that SET8 potentiated radiotherapy of carcinomas. As new inhibitors of SET8 are synthesized and tested in preclinical and clinical settings, combining SET8 inhibitors with radiation warrants consideration for precise radiotherapy.

Quality of life and related factors in patients with interstitial cystitis/bladder pain syndrome / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the quality of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS), to compare the difference between IC/BPS and overactive bladder (OAB) pain syndrome, and to explore the related factors affecting the quality of life of IC/BPS patients.@*METHODS@#The demographic data of female outpatients with IC/BPS in Beijing Hospital and other medical centers in China were collected. The quality of life of the patients was investigated by multi-angle questionnaires and compared with the data of OAB patients. According to the influence degree of quality of life, the patients with IC/BPS were divided into mild-moderate group and severe group.@*RESULTS@#In this study, 109 patients with IC/BPS were included. The average age was (46.4±14.3) years and the average course of disease was (39.4±51.6) months. Compared with the OAB patients, the patients in IC/BPS group had a longer average course of disease (P=0.008), a lower proportion of the patients of first visit for the disease (P < 0.001), a higher score of the American Urological Association symptom index (AUA-SI) (P < 0.001), a lower body mass index (BMI) ratio (P=0.016), and a lower incidence of constipation (P=0.006). IC/BPS had the greatest impact on family life, followed by social activity. The score of IC/BPS related symptoms on family life was significantly higher than that of the OAB group (P=0.003). The top three symptoms of the IC/BPS patients were pain (45%), frequency (28%) and urgency (17%). The score of quality of life in the IC/BPS patients was significantly higher than that in the OAB patients (P < 0.001). Caffeine intake (P=0.034) and constipation (P=0.003) might be the factors influencing the quality of life of the patients with IC/BPS.@*CONCLUSION@#IC/BPS has a great influence on the quality of life of patients. Caffeine intake and constipation may be related factors affecting the quality of life of patients with IC/BPS. Urologists should recommend changes in diet and lifestyle to reduce symptoms and improve the patients' quality of life.

Analysis of semen quality of 38 905 infertile male patients during 2008-2016 in Wenzhou, China / 亚洲男科学杂志(英文版)

This study analyzed the trend in semen quality of infertile male patients in Wenzhou, China, based on the data obtained from 38 905 patients during 2008-2016 in The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). The results showed that only 24.9% of the patients had normal semen quality. For the semen quality of infertile male patients, that of the workers and 40-year-olds was significantly worse than the other occupational and age groups. For all the infertile patients, low semen volume, asthenozoospermia, and teratozoospermia accounted for 8.4%, 50.5%, and 54.1%, respectively. During 2008-2016, the annual mean percentage of fast forward motile spermatozoa, percentage of total forward motile spermatozoa, and percentage of spermatozoa with normal morphology decreased linearly with slopes of -2.11, -2.59, and -0.70, respectively. The proportion of patients with asthenozoospermia and multi-abnormal spermatozoa increased during 2008-2016 with slopes of 4.70 and 4.87, respectively, while for low semen volume, it decreased with a slope of -0.47 in the same time period. The proportion of patients with teratozoospermia increased from 2008 to 2011 and from 2011 to 2016 with slopes of 17.10 and 2.09, respectively. In general, the deteriorating trend of semen quality of infertile male patients in Wenzhou was obvious. Future efforts should be made to reveal the adverse influences on semen quality, such as occupational exposure, environmental quality, and living habits. Furthermore, more pervasive reproduction health education is necessary.

Research Progress on Chemical Constituents and Pharmacological Effects of Asari Radix et Rhizoma / 中国实验方剂学杂志

Asari Radix et Rhizoma （ARR） is a traditional Chinese medicine for relieving exterior syndrome， and its roots and stems contain rich chemical components， including volatile oils （terpenoids， aromatics and aliphatics）， lignans， flavonoids， etc. Clinically， it has been traditionally used for the treatment of diseases such as phlegm and cough， anemofrigid cold， rheumatic arthralgia due to its ability to spread cold. Modern pharmacological studies have shown that ARR played beneficial roles in analgesic， anti-inflammatory， antitussive， antiasthmatic， antiviral， antibacterial， sedative， antioxidative， and antidepressant responses， antihypertension， as well as tumor suppression. The current studies on the chemical composition of ARR mainly focused on volatile components， and little information is available for the occurrence and pharmacological effects of non-volatile components. In addition， there is a lack of clear classification of chemical components and the distribution of chemical components in medicinal parts and the origin of species. Therefore， in this study， the authors reviewed a large number of literature on the chemical compositions and pharmacological effects of ARR， and hoping to provide a reference for further pharmacological research and the new drug development of ARR.

The sphingosine-1-phosphate/RhoA/Rho associated kinases/myosin light chain pathway in detrusor of female rats is down-regulated in response to ovariectomy / 中华医学杂志(英文版)

BACKGROUND@#Dysuria is one of the main symptoms of genitourinary syndrome of menopause, which causes serious disruption to the normal life of peri-menopausal women. Studies have shown that it is related to decrease of detrusor contractile function, but the exact mechanism is still poorly understood. Previous results have suggested that the sphingosine-1-phosphate (S1P) pathway can regulate detrusor contraction, and this pathway is affected by estrogen in various tissues. However, how estrogen affects this pathway in the detrusor has not been investigated. In this study, we detected changes of the S1P/RhoA/Rho associated kinases (ROCK)/myosin light chain (MLC) pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.@*METHODS@#Thirty-six female Sprague-Dawley rats were randomly divided into SHAM (sham operation), OVX (ovariectomy), and E groups (ovariectomy + estrogen), with 12 rats in each group. We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting, respectively. We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay. Finally, we compared results between the groups with one-way analysis of variance.@*RESULTS@#The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased, as compared with SHAM group. The percent decreases of the components in the S1P pathway were as follows: sphingosine kinase 1 (mRNA: 39%, protein: 45%) (both P  0.05). The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows: ROCK2 (protein: 41%, mRNA: 36%) (both P  0.05). In addition, all of the above-mentioned decreases could be reversed after estrogen supplementation (E group vs. SHAM group) (all P > 0.05).@*CONCLUSION@#In this study, we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor, which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.

Isolation and identification of endophytic fungi from Chelidonium majus and their antifungal activity / 中国中药杂志

In order to find new source of antifungal agents, eleven cultivable endophytic fungi were isolated from the roots,stems and leaves of Chelidonium majus by traditional method. Seven of them were identified as Colletotrichum(L1, L2, L3, S1, S3, S4, S5), and three of them were identified as Fusarium(R1,R2,R3) by morphological features and molecular biological technology. The antifungal activity test showed that all the tested fungi displayed some inhibitory activity against five common plant pathogens(C. gloeosporioides, Curvularia lunata, Pyricularia oryza, Alternaria alternate and A. brassicae), and their inhibition rate of some test items were over 60%. Among them, R1, S2, S3 and S4 were more potent than others. This study enriches the understanding of endophytes from Ch. majus and provides a basis for the study of new microbial fungicides.

Efficacy of CD19 Chimeric Antigen Receptors T Cells in the Treatment of Relapsed Patients with B Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To study the long-term efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of relapsed patients with B-cell acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#A total of 7 patients with B-cell ALL relapsed after allo-HSCT were treated with CD19 CAR-T cells from September 2015 to March 2018. Among them, 6 had hematological recurrence and 1 had positive of MRD. They all were treated with a single infusion of CAR-T cells. FC chemotherapy regimen was administered before transfusion. The median number of CAR-T cells transfused was 6.0 (range 4.0-8.6) )×10/kg. Long-term efficacy and toxicity were evaluated.@*RESULTS@#Bone marrow examination performed at d 30 after CAR-T infusion showed that all 7 patients achieved complete remission and MRD negative, grade I CRS for 1 case and grade II CRS for 6 cases, two of them had mild neurotoxicity, which was controlled by treatment. Two patients presented grade VI intestinal GVHD after CAR-T infusion. The median follow-up time was 18 months (range 12-42). Follow-up showed that two patients relapsed at 9 months and 14 months after treatment, out of 2 patients one died of progressive disease and the other reachived the hematological remission, but MRD was positive after CD22 CAR-T cell therapy. At present, five patients are disease-free survival, moreover showed complete donor chimerism. One year after CAR-T cell therapy, the results of immune reconstitution showed that CD4 level was more than 300×10/L in 5 patients who disease-free survived. Among them, 3 patients had poor recovery of immunoglobulin and received gamma globulin replacement therapy.@*CONCLUSION@#All patients are followed up for at least one year. The preliminary efficacy and safety are satisfactory. CAR-T cell infusion is an effective method for the treatment of B-ALL recurrence after allo-HSCT.

Health Financial Analysis on the Department Budget and the Differences of Final Accounts in the National Health and Family Planning Commission / 中国卫生经济

Objective:To analyze the differences between department budget and final accounts of health finance in the National Health and Family Planning Commission(NHFPC).Methods:It used the degree of deviation to evaluate the differences between department budget and final accounts with the data of NHFPC department revenue and expenditure from 2010 to 2016.Results:The department over-budget revenue and expenditure was large in scale,with high percentage in budget.The degree of deviation of over-budget expenditure had declined obviously since 2013,but over-budget revenue was still high.Income from undertakings accounted for a high proportion and grew fast.The growth rate of health cost was higher than that of GDP and resident income.Conclusion:It recommended to enhance the theory of health finance,deepen payment method reform,improve the department budget management mechanism,speed up to establish modem scientific health financial system and reduce health costs and residents' medical burdens.

Role of mast cells in experimental autoimmune prostatitis in rats / 中华男科学杂志

Objective@#To investigate the role of mast cells in chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS).@*METHODS@#Forty-five male SD rats were equally randomized into a control, an experimental autoimmune prostatitis (EAP) model, and an intervention group. The EAP model was made in the latter two groups by subcutaneous injection of mixed suspension of complete Freund's adjuvant and prostate tissue, while the controls were treated subcutaneously with 0.9% sodium chloride. Tactile allodynia was quantified in the pelvic region of the control and EAP animals using Von-Frey filaments at 5, 10, 20, 30 and 40 days. After successful establishment of the EAP model, the rats of the intervention group were injected intraperitonieally with cromolyn sodium for 10 days, and meanwhile tactile allodynia was detected in the rats of the intervention and EAP model groups every other day. Then the prostates of the rats were harvested for HE and toluidine blue staining and measurement of the expression of mast cell tryptase by immunohistochemistry and Western blot.@*RESULTS@#Von-Frey assessment showed a more severe pelvic pain in the EAP model than in the control rats, but milder in the intervention group than in the EAP models. HE staining revealed infiltration of lymphocytes and neutrophils in the prostate and congestion surrounding the gland in the EAP model rats, but none in the controls. However, both the infiltration and congestion were significantly alleviated in the intervention group. Toluidine blue staining shown that. Compared with the control group, the total count of mast cells and the number degranulated mast cells were markedly increased in the EAP models (P <0.01) but decreased in the intervention group (P <0.05). Both immunohistochemistry and Western blot manifested that the expression of tryptase in the mast cells was remarkably upregulated in the EAP (both P <0.01) but down-regulated in the intervention group (P <0.05 and P <0.01).@*CONCLUSIONS@#Both the total count of mast cells and the number of degranulated mast cells are significantly increased in the prostate of EAP rats. Mast cells are one of the most important mediators of type Ⅲ prostatitis-induced chronic pelvic pain, which can be used as a target for the intervention and treatment of type Ⅲ prostatitis.

Clinical Significance of Monitoring T Lymphocyte Subsets after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between T lymphocyte subsets and the incidence of graft-versus-host disease (GVHD) and its clinical significance of monitoring the changes of T lymphocyte subsets dynamicly on 1, 3, 6, 12 month after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Twenty cases received allo-HSCT in Department of Hematology of General Hospital of Beijing Military Command from January 2013 to January 2014, including 10 males and 10 females with average age of 20.3 years (3-46 years old), among them 4 cases rectived HLA matched transplantation and 16 cases rectived HLA mismatched transplantation. The levels of T lymphocyte subsets including CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD4(+)CD25(high) FOXP3(+) in the peripheral blood were manitored with flow cytometry (FCM) on +1, +3, +6, +12 month after transplantation dynamicly.</p><p><b>RESULTS</b>(1) Follow up to March 2015, the levers of CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD4(+) CD25(high) FOXP3(+) showed a different degree of recovery after transplantation for all cases and returned to the lever of pre-transplantation on 12 month basically, and CD8(+) T cells recovered earlier than CD4(+) T cells, while the decrease of CD4(+) T cells lasted more than 1 year; The proportion inversion of CD4(+)/CD8(+) also lasted for more than 1 year;(2) The level of CD4(+) CD25(high) FOXP3(+) in patients with acute GVHD was lower than that in patients without acute GVHD.</p><p><b>CONCLUSION</b>The dynamic monitoring of the T lymphocyte subsets, especially CD4(+) CD25(high) FOXP3(+) after transplantation has importent clinical significance, it can forecast the incidence of acute GVHD before symptoms appeared; the dynamic monitoring of the T-lymphocyte subsets also can be used as reference indicator for prediction of GVHD, theraby it can reduce mortality of patients after transplantation.</p>

Clinical Efficacy of Haploidentical Allo-HSCT of Reduced Intensity Preconditioning Combined with Induced Immune Tolerance after Transplantation for Severe Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of haploidentical allo-HSCT in combination of reduced intensity preconditioning combined with cyclophosphamid (CTX)-induced immune tolerance after transplanitation for treatment of severe aplastic anemia (SAA).</p><p><b>METHODS</b>A total of 15 patients with SAA received the haploidentical allo-HSCT of reduced intensity preconditioning combined with CTX-induced immune tolerance after transplartation in the General hospital of Beijing military command of chinese PLA from June 2012 to December 2014. The reduced intensity preconditioning regimen consisted of CTX, fludarabine, busulfex and amti-lymphocyte immunoglobin; the immune tolerance was induced with CTX (50 mg/kg·d) on day 3 after transplantation; the HSC donors were father and mother of patients. The GVHD was prevented by inmunosuppression consisted of cyclosporine A(CsA), methotrexate and tacrolimus. The aduvese reaction and disease-free survival (DFS) were observed in all the patients.</p><p><b>RESULTS</b>All the SAA patients achieved hematopoietic reconstitution with 100% donor hematopoiesis, and all the T lymphocyte subsets increased. Out of 15 patients, 3 cases died of complication, and the DFS rate was 80% with a median follow-up of 19.8 month (6-36 months).</p><p><b>CONCLUSION</b>The haploidentical allo-HSCT of reduced intensity preconditioning combined with CTX-induced immune tolerance after transplantation is safet and effective for SAA patients, that may be applied to clinical therapy.</p>

Advances of the interaction between valproic acid and carbapenem antibiotics / 中国药学杂志

To critically evaluate the mechanisms of the interaction between valproic acid and carbapenem antibiotics. Research about the interaction between valproic acid and carbapenem antibiotics related case reports those were indexed from the Pubmed database. Studies to explain the decrease were carried out using rats and monkeys by the following mechanism; absorption, distribution, metabolism, and excretion of valproic acid. Carbapenem antibiotics induced a decrease of plasma concentration of valproic acid in epileptic patients during valproic acid therapy, resulting in the recurrence of epileptic seizures. Therefore, therapy with valproic acid and carbapenem antibibiotics should be avoided.

Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats / 中国天然药物

The present study was designed to investigate the effects of Laminaria japonica (Laminaria) on pharmacokinetics of glycyrrhetinic acid (GA) following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid (GL). The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter Tmax. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.

Isolation and immunomodulatory activity of bursal peptide, a novel bursal peptide from the chicken bursa of Fabricius

The bursa of Fabricius (BF), which is unique to birds, serves as the central humoral immune organ and plays a significant role in B lymphocyte differentiation. In this study, a new bursal peptide (BP-IV) was isolated from BF, which promoted colony-forming unit pre-B formation and regulated B cell differentiation. BP-IV also exerted immunomodulatory effects on antigen-specific immune responses via both humoral and cellular immunity in chicken and mice that had been immunized with inactivated avian influenza virus (AIV; H9N2 subtype), including enhancing AIV-specific antibody and cytokine production. The results of this study provided novel insights into the use of a potential candidate reagent for B cell development and future immuno-pharmacological use.

The potential molecular effects of bursal septpeptide II on immune induction and antitumor activity

The bursa of Fabricius (BF) is the acknowledged central humoral immune organ in birds. Bursal septpeptide II (BSP-II) is an immunomodulatory bioactive peptide isolated from BF. To understand the effects of BSP-II on immune induction, gene expression profiles of hybridoma cells treated with BSP-II were evaluated. Pathway analysis showed that regulated genes were involved in cytokine-cytokine receptor interactions, T cell receptor signaling pathway, and pathway in cancer. It was observed that BSP-II reduced tumor cells proliferation and stimulated p53 expression. These results indicate potential mechanisms underlying the effects of the humoral immune system on immune induction, including antitumor activities. Our study has provided a novel insight into immunotherapeutic strategies for treating human tumors.

Therapeutic efficacy of second allo-HSCT for aplastic anemia after failure of first allo-HSCT / 中国实验血液学杂志

This study was purposed to evaluate the curative efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) after failure of the first allo-HSCT in aplastic anemia patients, the cause of implant failure after allo-HSCT and clinical data of 10 severe aplastic anemia (SAA) patients in the second allo-HSCT were retrospectively analyszed. The second HSCT conditioning programs include: cyclophosphamide (CTX) + fludarabine (FLU)+ anti-thymocyte globulin (ATG) combination chemotherapy for 3 cases; CTX + FLU + white busulfan (Bu) + ATG combination chemotherapy for 7 cases. The prevention regimen of graft-versus-host disease (GVHD) include cyclosporine (CsA), mycophenolate mofetil (MMF) and methotrexate (MTX). The median count of mononuclear cell infusion was 12.17 (5.99-18.12)×10(8)/kg. The CD34(+) cell count was 5.2 (3.8-10.9)×10(6)/kg. The results showed that 10 evaluable patients achieved hematopoietic reconstitution with absolute neutrophil >0.5×10(9)/L, platelets >20×10(9)/L at 15d (8-21d) and 17d (11-27d) after transplantation. The grade I aGVHD occurred in 2 case, grade II in 1 case, chronic GVHD in 3 cases. Transplant-related deaths occurred in 4 cases. The disease-free survival rate, transplant-related mortality, GVHD after transplantation were 60%, 40% and 50% respectively. It is concluded that the second allo-HSCT is an effective therapy for aplastic anemia after allo-HSCT implant failure.

Retrospective analysis of therapeutic efficacy of haploidentical allogeneic hematopoietic stem cell transplantation for severe aplastic anemia / 中国实验血液学杂志

This study was purposed to investigate the therapeutic efficacy of haploidentical allogeneic hemopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA), and evaluate the safety of this treatment by retrospective analysis. A total of 21 patients with SAA (13 cases of SAA-I, 8 cases of SAA-II) were treated with haploidentical allo-HSCT. Donors were the relatives of the patients (12 were the parents, 9 were the siblings). The conditioning regimen contained cyclophosphamide, fludarabine and antithymocyte globulin. Methylaminopterin, mycophenolate mofetil and cyclosporin A were used for preventing graft versus host disease (GVHD). The chimerism rate was monitored periodically after successful graft. The long survival rate, incidence and severity of complication, such as GVHD, infection, and so on were analyzed. The results showed that 15 out of 21 patients were survived for 16 (3-46) months, survival rate was 71.4%. Graft tailure happened in one case who died of mycetes septicemia at 43 days after allo-HSCT. Two patients died of pulmonary infection at 6 days and 10 days respectively after transplantation. Rejection happened in one case at 3 months who died of pulmonary infection at 17 days after the second transplantation with the same donor. Two patients died of IV grade intestinal GVHD at 35 days and 52 days. GVHD occurred in 14 of 21 patients, the accumulative incidence was 66.7%, 5 cases of them were severe. It is concluded that the therapeutic efficacy of haploidentical allo-HSCT is effective for SAA and with slighter complications.