Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area / 中国实验血液学杂志

OBJECTIVE@#To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area.@*METHODS@#The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes.@*RESULTS@#Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05).@*CONCLUSION@#The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.

Effects of massive blood transfusion on serum electrolyte balance and inflammatory factor levels in patients with severe trauma / 中国基层医药

Objective:To investigate the effects of massive blood transfusion on serum electrolyte balance and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with severe trauma.Methods:A total of 83 patients with severe trauma who received treatment in Eastern District of LiHuili Hospital, Ningbo Medical Center between July 2019 and December 2020 were included in this study. All of them underwent blood transfusion. They were divided into massive blood transfusion group ( n = 29) and general blood transfusion group ( n = 54) according to the volume of blood transfused. Changes in coagulation function, electrolyte, liver-kidney function and inflammatory factor levels pre- and post-blood transfusion were compared between massive blood transfusion and general blood transfusion groups. Results:At 1 day after blood transfusion, activated partial thromboplastin time (APTT) and prothrombin time (PT) in the massive blood transfusion group were (45.64 ± 2.78) seconds and (17.71 ± 2.08) seconds, respectively, which were significantly longer than those in the general blood transfusion group [(41.02 ± 2.80) seconds, (15.35 ± 1.72) seconds, t = 5.53, 7.18, P < 0.05). At 1 day after blood transfusion, levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the massive blood transfusion group were (1.84 ± 0.32) μg/L, (113.72 ± 13.34) ng/L, (28.94 ± 4.22) mg/L, respectively, which were significantly increased compared with those measured before blood transfusion [(1.28 ± 0.29) μg/L, (95.18 ± 10.64) ng/L, (16.48 ± 3.37) mg/L, t = 6.98, 5.85, 12.42, all P < 0.05]. Levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the general blood transfusion group were (1.34 ± 0.27) μg/L, (98.54 ± 9.62) ng/L, (20.05 ± 3.30) mg/L, respectively at 1 day after blood transfusion, which were significantly increased compared with those measured before blood transfusion [(1.23 ± 0.26) μg/L, (94.22 ± 8.82) ng/L, (16.16 ± 3.39) mg/L, t = 2.15, 2.43, 6.04, all P < 0.05]. At 1 day after blood transfusion, serum levels of tumor necrosis factor-α and C-reaction protein in the massive blood transfusion group were significantly higher than those in the general blood transfusion group ( t = 7.53, 10.59, both P < 0.05). At 1 day after blood transfusion, serum levels of K + and Ca 2+ in the massive blood transfusion group were (3.56 ± 0.54) mmol/L and (1.87 ± 0.28) mmol/L, respectively, which were significantly lower than those in the general blood transfusion group [(4.27 ± 0.34) mmol/L, (2.26 ± 0.24) mmol/L, t = 7.34, 6.65, both P < 0.05]. Serum levels of alanine aminotransferase and aspartate aminotransferase in the massive blood transfusion group were (52.46 ± 20.27) U/L, (82.37 ± 31.15) U/L, respectively, which were significantly higher than those in the general blood transfusion group [(37.57 ± 10.31) U/L, (49.35 ± 10.14) U/L, t = 4.44, 7.14, both P < 0.05)]. The incidence of abnormal liver function in the massive blood transfusion group was significantly higher than that in the general blood transfusion group [62.07% (18/29) vs. 29.63% (16/54), χ2 = 10.13, P < 0.05)]. Conclusion:The internal environment of patients with severe trauma will change after massive blood transfusion. Their coagulation function, inflammatory factors, liver function and electrolyte balance should be monitored in time.

A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis / 中华血液学杂志

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

Effect of Jiedu Huayu Granules on Inflammatory State of Patients with Chronic Hepatic Failure with Toxic Heat and Stasis Syndrome / 中国实验方剂学杂志

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ2=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ2=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.

Relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity / 中华内分泌代谢杂志

Objective:Explore the relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity(baPWV) in community population.Methods:Questionnaire, physical examination, blood tests, and baPWV detection were applied to a community based population. Finally, 3 912 subjects with complete data were included in the study. The relationship between sleep duration, time to fall asleep and PWV was evaluated with binary logistic regression analysis. Results:Being adjusted for age, sex, prevalence of diabetes, sleep condition, body mass index, blood glucose, blood pressure, dyslipidemia, ankle-brachial index, sleep duration and time to fall asleep were correlated with PWV. The risk of PWV abnormalities was increased in the≥8 h group compared to the 6-8 h group( OR=1.155, 95% CI 0.995-1.367, P=0.037). The risk of abnormalities PWV was higher in the group with sleep time after 00: 00 than in the group -23: 00( OR=1.482, 95% CI 1.008-2.179, P=0.045). Conclusion:Long sleep duration(≥8 h) and late sleep time(after 00: 00) may be associated with higher risk of atherosclerosis.

Mechanism of Traditional Chinese Medicine and Its Compound on Liver Fibrosis / 中国实验方剂学杂志

Hepatic fibrosis refers to the pathological process of abnormal proliferation of intrahepatic connective tissue caused by various pathogenic factors, resulting in the excessive accumulation of extracellular matrix (ECM) in the liver and the formation of fibrous scar. Its continuous deterioration will gradually develop into liver cirrhosis, liver failure, liver cancer and other serious liver diseases. Because liver fibrosis and early liver cirrhosis can be reversed, it is very important to control the reversible process of liver fibrosis for the prevention and treatment of liver cirrhosis and liver cancer. In recent years, it has been found that traditional Chinese medicine(TCM) has the characteristics of multi-target, less toxic and side effects and good effect in the treatment of liver fibrosis. In this paper, the mechanism of anti-hepatic fibrosis of TCM and its compound was summarized. TCM can regulate transforming growth factor-β (TGF-β), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and other growth factors to inhibit the activation of (HSCs) and induce the apoptosis of activated HSCs, promote the expression of adiponectin and inhibit the secretion of leptin, inhibit the inflammatory reaction of liver, resist oxidant stress, inhibit the capillarization of hepatic sinusoidal endothelial cells, so as to effectively prevent the progress of liver fibrosis. Therefore, TCM can inhibit the development of liver fibrosis through multi-mechanism and multi-level, and is one of the important means to treat liver fibrosis.

Allogeneic CAR-T for treatment of relapsed and/or refractory multiple myeloma: four cases report and literatures review / 中华血液学杂志

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

miR-9 inhibits the proliferation and migration of esophageal cancer EC109 cells by regulating GOLPH3 / 临床检验杂志

Objective@#To investigate the expression level of miR-9 in esophageal cancer and its effect on the biological function of esophageal cancer cells. @*Methods@#The expression levels of miR-9 and Golgi phosphoprotein 3 (GOLPH3) in esophageal cancer and its adjacent tissues were detected by real-time fluorescence quantitative PCR (qRT-PCR). The miR-9 mimics was transfected into esophageal cancer EC109 cells, and the expression level of miR-9 was detected by qRT-PCR. The effects of overexpression of miR-9 on the biological function of EC109 cells were determined by the MTT assay, plate colony formation assay, Transwell migration assay and flow cytometry. The wild and mutant GOLPH3 double luciferase reporter gene vectors were constructed, and luciferase activity was detected. The effects of overexpression of miR-9 on the expression levels of GOLPH3 mRNA and protein were detected by qRT-PCR and Western blot. @*Results@#Compared with the adjacent tissues, the expression level of miR-9 in esophageal cancer tissues decreased significantly (P＜0.01), while that of GOLPH3 increased significantly (P＜0.01). Compared with the negative control group, the expression level of miR-9 in EC109 cells transfected with miR-9 mimics increased significantly (P＜0.01), and the proliferation and migration ability of the EC109 cells decreased obviously (P＜0.01). The cell cycle of the EC109 cells was blocked in G2/M phase (P＜0.01). The dual luciferase reporter assay, qRT-PCR and Western blot confirmed that miR-9 could bind with GOLPH3 specifically (P＜0.01), and mediate the degradation of GOLPH3 mRNA (P＜0.01), which led to the decrease of GOLPH3 protein expression level (P＜0.05). @*Conclusion@#MiR-9 is low expression in esophageal cancer, and may participate in the occurrence and development of esophageal cancer by regulating GOLPH3.

Inhibitory effect of KyoT2 overexpression on proliferation and migration of airway smooth muscle cells in mice with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of KyoT2 on the proliferation and migration of airway smooth muscle cells (ASMCs) in mice with asthma.</p><p><b>METHODS</b>Ovalbumin (OVA) was used to establish the asthmatic model of airway remodeling in BALB/c mice. ASMCs were isolated and cultured, and primarily cultured ASMCs were used as the control group. The expression of KyoT2 in ASMCs was measured in the control and asthma groups. After the ASMCs from asthmatic mice were transfected with pCMV-Myc (empty vector group) or pCMV-Myc-KyoT2 plasmid with overexpressed KyoT2 (KyoT2 expression group) for 48 hours, RT-PCR and Western blot were used to measure the mRNA and protein expression of KyoT2, the MTT assay and BrdU assay were used to measure the proliferation of ASMCs, and Transwell assay was used to measure the migration of ASMCs. Western blot was used to determine the effect of KyoT2 overexpression on the protein expression of RBP-Jκ, PTEN, and AKT.</p><p><b>RESULTS</b>Compared with the control group, the asthma group had significantly downregulated expression of KyoT2 in ASMCs, and the KyoT2 expression group had significantly upregulated expression of KyoT2 in ASMCs (P<0.05). Compared with the empty vector group, overexpressed KyoT2 significantly inhibited cell proliferation and migration, downregulated the expression of RBP-Jκ and AKT, and upregulated the expression of PTEN.</p><p><b>CONCLUSIONS</b>Overexpressed KyoT2 can inhibit the proliferation and migration of ASMCs through the negative regulation of RBP-Jκ/PTEN/AKT signaling pathway.</p>

Study on performance evaluation indicators of central venous pressure measuring system for critical patients in clinical trials / 中国实用护理杂志

Objective We aimed to study the performance evaluation indicators of central venous pressure (CVP) measuring system for ICU patients in clinical trials and discuss its impact factors.Methods Ac-cording to the performance evaluation indicators of CVP measuring system based on the Delphi method,a form was created to evaluate the continuous CVP monitoring of 197 ICU patients and then the data were collected.A comparative analysis was performed to verify the factors affecting the performance of CVP measuring system.Results The performance of CVP measuring system was affected by the number of threeway switches,vasoactive drugs and positive end-expiratory pressure,the statistical value was 8.577,-6.773and 3.244.There were no statistically significant differences with respect to performance evaluation indicators of CVP measuring system among the patients with different body positions.Conclusions The performance evaluation indicators of CVP measuring sys-tem proves to be feasible and practical by clinical empirical research.Their influencing factors were dis-cussed and they offer a valuable reference for the determination of the performance of CVP measuring sys-tem in clinical practice.

Clinical application of the OPLAC for hip replacement surgery / 重庆医学

Objective To observe the efficacy ,safety and patient acceptance of the artificial airway with the oro‐pharyngo‐laryn‐gead airway cap(OPLAC) for hip replacement surgery in patients with intravenous‐inhalation combined anesthesia .Methods Sev‐enty eight cases of patients receiving the hip replacement surgery were included ,42 patients were to be adopted to establish artificial airway with the OPLAC for intravenous‐inhalation combined anesthesia ,another 36 patients treated with heath side‐lying position hypobaric spinal‐epidural anesthesia .There are two groups ,the oro‐pharyngo‐laryngead airway cap group(OPLAC ,n=42) and hy‐pobaric combined spinal‐epidural anesthesia group (CESA ,n=36) .Monitor the changes of respiratory and circulatory parameters of the two groups before the start of anesthesia ,anesthetic after 10 min ,30 min ,1 h ,and handling marrow ,observing occurrence of complications (delirium ,sore throat ,nausea ,vomiting ,deep vein thrombosis) ,following up the degree of satisfaction of patients and surgeons for anesthesia .Results The respiratory and circulatory parameters of the OPLAC group during anesthesia induction and maintenance were relatively stable ,on the other hand ,significant cyclic inhibition (blood pressure and heart rate decresing ) and re‐spiratory rate declining were observed in the CESA group after anesthesia ,cases with the use of atropine and dopamine significantly more than OPLAC group .The circulation and breath in the OPLAC group were relatively stable when handling marrow ,while cir‐culation fluctuating Significantly in the CESA group (blood pressure decreasing and heart rate increasing ) .The incidence of delirium in the CESA group was significantly higher than OPLAC group .The patient satisfaction of the OPLAC group was significantly bet‐ter than the CESA group .Conclusion The artificial airway with OPLAC for hip replacement surgery in patients with intravenous‐inhalation combined anesthesia is safe ,effective ,and satisfactory .

Relationship of Adiponectin and Insulin Resistance in Patients with Chronic Kidney Disease / 天津医药

Objective To investigate the changes of serum and urinary adiponectin (ADPN) levels and insulin resis-tance (IR) states in patients with chronic kidney disease (CKD), and to explore their relationship thereof. Methods A total of 487 patients with CKD stages 2-5 were enrolled in this study, and 30 healthy subjects were served as control group. The se-rum ADPN levels in urine samples were examined by ELISA. The level of fasting insulin (FINS) was detected by radioimmu-noassay. Blood routine test, liver and kidney functions, blood glucose, serum lipids, 24 h urinary protein excretion and endoge-nous creatinine clearance rate (Ccr) and body mass index (BMI) were observed and calculated. The differences of ADPN lev-els in serum and urine samples and homeostasis model assessment for insulin resistance (Homa-IR) were compared between groups. Results The serum and urine ADPN levels and Homa-IR were higher in CKD patients than those of controls (P＜0.05). With the decline in renal function, the ADPN and Homa-IR levels were increased gradually (P＜0.05). The value of se-rum ADPN was significantly higher in patients with CKD stages 3-5 and high Homa-IR. The ADPN levels and Homa-IR were positively related to lipid parameters and 24 h urinary protein, and negatively correlated with hemoglobin and serum al-bumin in patients with CKD (P ＜ 0.05). Conclusion CKD patients had higher ADPN level and more significant IR. The ADPN and IR were correlated with serum lipids, hemoglobin, albumin and urinary protein. Dynamic monitor of ADPN level may have clinical significance in judging metabolic disorders in CKD patients.

Construction of a new oncolytic virus oHSV2hGM-CSF and its anti-tumor effects / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to construct a new oncolytic virus oHSV2hGM-CSF and evaluate its oncolytic activity in vitro and in vivo in parallel with oHSV1hGM-CSF.</p><p><b>METHODS</b>oHSV2hGM-CSF was a replication-competent, attenuated HSV2 based on the HG52 virus (an HSV2 strain). It was engineered to be specific for cancer by deletion of the viral genes ICP34.5 and ICP47 and insertion of the gene encoding hGM-CSF. To measure the in vitro killing effect of the virus, 15 human tumor cell lines (HeLa, Eca-109, PG, HepG2, SK/FU, CNE-2Z, PC-3, SK-OV3, A-549, 786-0, MCF-7, Hep-2, HT-29, SK-Mel-28, U87-MG) and mouse melanoma (B16R) cell line were seeded into 24-well plates and infected with viruses at MOI = 1 (multiplicity of infection, MOI), or left uninfected. The cells were harvested 24 and 48 hours post infection, and observed under the microscope. For animal studies, the oncolytic viruses were administered intratumorally (at 3-day interval) at a dose of 2.3 x 10(6) PFU (plaque forming unit, PFU) for three times when the tumor volume reached 7-8 mm3. The tumor volume was measured at 3-day intervals and animal survival was recorded.</p><p><b>RESULTS</b>Both oHSV2hCM-CSFand oHSV1hGM-CSF induced widespread cytopathic effects at 24 h after infection. OHSV2hGM-CSF, by contrast, produced more plaques with a syncytial phenotype than oHSV1hGM-CSF. In the in vitro killing experiments for the cell lines HeLa, HepG2, SK-Mel-28, B16R and U87-MG, oHSV2hGM-CSF eradicated significantly more cells than oHSV1hGM-CSF under the same conditions. For the mouse experiments, it was observed that oHSV2hGM-CSF significantly inhibited the tumor growth. At 15 days after B16R tumor cells inoculation, the tumor volumes of the PBS, oHSV1hGCM-CSF and oHSV2hGM-CSF groups were (374.7 +/- 128.24) mm3, (128.23 +/- 45.32) mm3 (P < 0.05, vs. PBS group) or (10.06 +/- 5.1) mm3 (P < 0.01, vs. PBS group), respectively (mean +/- error). The long term therapeutic effect of oHSV2hGM-CSF on the B16R animal model was evaluated by recording animal survival over 110 days after tumor cells inoculation whereas all the mice in the PBS group died by day 22 (P < 0.01). The anti-tumor mechanism of the newly constructed oHSV2hGM-CSF against B16R cell tumor appeared to include the directly oncolytic activity and the induction of anti-tumor immunity to some degree.</p><p><b>CONCLUSION</b>The findings of our study demonstrate that the newly constructed oHSV2hGM-CSF has potent anti-tumor activity in vitro to many tumor cell lines and in vive to the transplanted B16R tumor models.</p>

Generation of a herpes simplex virus-permissive mouse melanoma cell line B16RHSV / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To generate an oncolytic herpes simplex virus (oHSV) permissive mouse melanoma cell line B16RHSV, preserving the tumorigenic ability in syngeneic mice.</p><p><b>METHODS</b>The herpes simplex virus entry mediator (HVEM) gene was amplified by PCR from human melanoma cell line A375, and cloned into pGEM-T Easy vector for sequencing. The HVEM gene was then cloned into pcDNA3 vector to generate pcDNA3-HVEM for transfection of mouse melanoma cell line B16-F10 cells. After that, the putative transfected cells were selected in full growth medium containing G418. The HVEM-expressing cells were isolated by immunomagnetic bead separation. The mouse melanoma cell line expressing oHSV receptor-HVEM, designated as B16RHSV, was generated. The permissibility of B16RHSV cells to oHSV infection was examined with green fluorescence protein (GFP)-expressing oHSV (oHSVGFP). To investigate the tumorigenic ability of both cells in vivo, 2×10(5) cells in 100 µl were subcutaneously inoculated into the right flanks of C57/BL mice.</p><p><b>RESULTS</b>In vitro, the B16RHSV mouse melanoma cells were shown by fluorescence microscopy capable of being infected by oHSVGFP. In vivo, the B16RHSV cells, like their wild type counterpart, grew to form melanoma in syngeneic mice.</p><p><b>CONCLUSION</b>A herpes simplex virus-permissive mouse melanoma cell line was established. Its tumorigenicity remained unchanged.</p>

Identification of occult disseminated tumor cells by recombinant herpes simplex virus expressing GFP (HSV(GFP)) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To develop a novel rapid protocol for the detection of occult disseminated tumor cells by a recombinant herpes simplex virus expressing GFP (HSV(GFP)).</p><p><b>METHODS</b>Tumor cells of seven cell lines were exposed to HSV(GFP) and then examined for GFP expression by fluorescence microscopy. Various numbers of tumor cells (10, 100, 1000, 10 000) were mixed into 2 ml human whole blood, separated with lymphocytes separation medium, exposed to HSV(GFP), incubated at 37°C for 6 - 24 h and then counted for the number of green cells under the fluorescence microscope. Some clinical samples including peripheral blood, pleural effusion, ascites, spinal fluid from tumor-bearing patients were screened using this protocol in parallel with routine cytological examination.</p><p><b>RESULTS</b>HSV(GFP) was able to infect all 7 tumor cell lines indicating that the HSV(GFP) can be used to detect different types of tumor cells. The detection sensitivity was 10 cancer cells in 2 ml whole blood. In the clinical samples, there were 4/15 positive by routine cytological examination but 11/15 positive by HSV(GFP), indicating a higher sensitivity of this new protocol.</p><p><b>CONCLUSION</b>Recombinant herpes simplex virus-mediated green fluorescence is a simple and sensitive technique for the identification of occult disseminated cancer cells including circulating tumor cells (CTCs).</p>

Impact of disease status on outcomes of allogeneic hematopoietic stem cell transplantation in patients with refractory and relapsed acute myeloid leukemia / 中国实验血液学杂志

The study was aimed to evaluate the impact of disease status on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory and relapsed acute myeloid leukemia (AML). 32 patients with refractory and relapsed AML received allo-HSCT after myeloablative conditioning regimen, including 17 patients in no-remission (NR) and 15 patients in complete remission (CR) at the time of transplant. Treatment related adverse events, relapse rate and leukemia free survival (LFS) were analyzed. The results showed that the parameters of sex, age, cytogenetic risk and transplant procedures were comparable between the two groups. 30 patients had successful engraftment, except one had graft failure and one died from severe veno-occlusive disease in the NR group. The incidences of aGVHD in NR group and CR group were 47.1% (8 patients) and 33.5% (5 patients) respectively. Out of comparable patients, 5 from 9 patients in NR group developed with cGVHD, and 4 from 11 patients in CR group were subjected to cGVHD. There were no statistic difference in incidences of aGVHD and cGVHD between two group. Compa-red with CR group, NR group had a higher treatment-related mortality (29.4% vs 14.3%, P = 0.392) and relapse rate (42.9% vs 26.7% P = 0.300), but there was no significant difference. With a median follow-up of 13 (1 - 124) months, 6 patients remained alive in both of the two groups, and the 2 year LFS of them were parallel (35.3% vs 40.0%, P = 0.267). Among these 32 patients, overall survival (OS) was better in patients with age < 35 years (P = 0.044) and with the appearance of cGVHD (P = 0.046). It is concluded that allo-HSCT is an effective salvage therapy for patients with refractory and relapsed AML, and the overall outcome seems unrelated to the disease status (NR or CR) before transplantation. As such, for refractory and relapsed AML patients in non-remission, performance of allo-HSCT to achieve long-term survival is feasible.

Study on status of needle-stick and other sharps injuries among healthcare workers in a general hospital / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To understand the prevalence of hospital healthcare workers (HCWs) with needle-stick and other sharps injuries, and to provide the basic data for intervention study.</p><p><b>METHODS</b>A retrospective investigation was conducted with questionnaires for needle-stick and other sharps injuries from January 1- to December 31 of 2009 among 1201 healthcare workers in a general hospital.</p><p><b>RESULTS</b>The total number of needle-stick and other sharps injuries among 1201 healthcare workers in 2009 was 4320, the number of needle-stick and other sharps injuries for each person was 3.58 and the incidence of needle-stick and other sharps injuries was 78.85 %. The subjects with the high risk of needle-stick and other sharps injuries were from the department of gynecology and obstetrics, surgical department, intensive care unit and emergency room, the incidences and the average numbers of episodes were 94.67% and 4.51 per person, 93.09% and 4.46 per person, 85.44% and 3.08 per person, 76.62 % and 4.55 per person in 2009, respectively. The operations resulting in the needle-stick and other sharps injuries were the breaking glass preparation (ampoule or vial), withdrawing needles, preparing sharp devices and performing an operation, the incidences were 46.96%, 30.97%, 25.73% and 14.49%, respectively. Needle-stick and other sharps injuries were mainly caused by ampoules, winged steel needle, disposable syringes, suture needles and scalpels, the incidences were 47.04%, 37.22%, 31.31%, 17.65% and 7.08%, respectively.</p><p><b>CONCLUSION</b>Healthcare worker are still at risk of needle- stick and other sharps injuries, which was related to the profession, department, medical manipulation and medical apparatus and instruments. Special and comprehensive measurements for preventing the needle-stick and other sharps injuries should be taken actively.</p>

Research progresses in the pathogenesis of anaplastic large cell lymphoma / 癌症

Anaplastic large cell lymphoma (ALCL) is a distinct subset of T-cell non-Hodgkin's lymphoma. As a consequence of its low incidence, general pathogenic consideration of ALCL is lacking. In this review, we summarize the pathogenesis, epidemiology, clinical manifestations, and treatment of ALCL, so as to better understand key stages of the development of this disease and provide valuable information for future treatment.

Quantitative analysis of HBV cccDNA from liver biopsy specimens in HBV carriers: correlation with serological makers and sera HBV DNA / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of sera HBV DNA and serological makers with hepatic tissue HBVcccDNA in chronic HBV carriers.</p><p><b>METHODS</b>Real time fluorescence quantitative polymerase chain reaction (RT-PCR) were used to detect HBV covalently closed circular DNA (cccDNA) and total intrahepatic HBV DNA from 30 needle-biopsy specimens as well as HBV DNA in sera in chronic HBV carriers. Quantification of the HBsAg, HBeAg in sera were quantified using Chemiluminescence immunoassay.</p><p><b>RESULTS</b>HBVcccDNA can be detected in chronic HBV carriers, which rang from 3.15 x 10(3) copies/mg to 1.06 x 10(7) copies/mg. There was a positive correlation between the cccDNA and HBVtDNA (r = 0.375, P < 0.05), but there was no correlation between the cccDNA and sera HBV DNA (P = 0.174). There was a positive correlation between cccDNA and sera HBsAg quantification (r = 0.562, P < 0.001) but no correlation with sera HBeAg qantification (r = 0.152, P > 0.05).</p><p><b>CONCLUSION</b>HBV cccDNA can be replicated stably in hepatic tissue in all chronic HBV carriers. HBV DNA in sera can not be indicated hepatic tissue cccDNA level. While HBsAg quantification in sera can be used as a marker of cccDNA quantification in hepatic tissue to some extent.</p>