Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).@*METHODS@#In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.@*RESULTS@#Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.@*CONCLUSIONS@#In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Molecular mechanism of ligustilide attenuating OGD/R injury in PC12 cells by inhibiting ferroptosis / 中国中药杂志

The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.

Effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the expression of Fas/FADD/Caspase-8 of death receptor pathway in rats with primary ovarian insufficiency / 中国针灸

OBJECTIVE@#To explore the effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the ovarian function in the rats with primary ovarian insufficiency (POI) and the potential effect mechanism based on the Fas/FADD/Caspase-8 of death receptor pathway.@*METHODS@#Forty-eight female SD rats were randomly divided into a blank group, a model group, a medication group and an acupuncture group, with 12 rats in each group. Except in the blank group, the rats in the other groups were intraperitoneally injected with cyclophosphamide to establish the POI model. In the acupuncture group, after successful modeling, the intervention was given with "Zhibian" (BL 54)-to- "Shuidao" (ST 28) needle insertion, once daily, 30 min in each intervention; and the duration of intervention was 4 weeks. In the medication group, estradiol valerate tablets were administered intragastrically, 0.09 mg•kg-1•d-1, for 4 weeks. The general situation and the estrous cycle of the rats were compared among groups. Using ELISA, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) in the serum were detected. HE staining was adopted to observe the morphological changes of ovarian tissue of rats. The protein expression of Fas, FADD and Caspase-8 in ovarian tissue was detected with immunohistochemistry and Western blot.@*RESULTS@#After modeling, except the rats of the blank group, the rats of the other groups had dry fur, lost hair, low spirits, reduced food intake, increased urination and loose stool. After intervention, the stool became regular gradually in the acupuncture group and the medication group. The percentage of estrous cycle disturbance was increased in the rats of the model group when compared with the blank group (P<0.01); in comparison with the model group, the percentages of estrous cycle disturbance were reduced in the acupuncture group and the medication group after intervention (P<0.01). When compared with the blank group, the body mass and E2 content in the serum were lower (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were increased (P<0.01) in the model group. Compared with the model group, the body mass and E2 contents in the serum were higher (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were reduced (P<0.01) in the acupuncture group and the medication group.@*CONCLUSION@#"Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion can effectively improve the ovarian function of POI rats, and its effect mechanism may be related to regulating the serum sex hormone levels, reducing the expression of Fas, FADD and Caspase-8 in ovarian tissue and retarding apoptosis of ovarian cells.

Effect of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on the expression of apoptosis-related factors in rats with premature ovarian insufficiency based on oxidative stress / 中国针灸

OBJECTIVE@#To explore the possible mechanism of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on premature ovarian insufficiency (POI) from the perspective of oxidative stress.@*METHODS@#Sixty female SD rats were randomly divided into a blank group, a model group, a sham acupuncture group, a medication group, and an acupuncture group, 12 rats in each group. Except the blank group, the rats in the remaining groups were intraperitoneally injected with cyclophosphamide to establish the POI model. After the model was successfully established, the rats in the acupuncture group were treated with acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28), with a depth of about 12 mm, and the needle was retained for 30 min; the acupuncture was given once a day, for a total of 4 weeks. The rats in the sham acupuncture group were treated with blunt-head needle to tap the skin surface of "Zhibian" (BL 54), without penetrating the skin, once a day for 4 weeks. The rats in the medication group were treated with estradiol valerate by gastric gavage for 4 weeks. After the intervention, the level of reactive oxygen species (ROS) in the ovarian tissue was detected by fluorescence probe; the expression of c-Jun N-terminal kinase (JNK), forkhead box O1 (FoxO1), tumor suppressor gene protein 53 (p53) and p53 up-regulated modulator of apoptosis (Puma) mRNA and protein in ovarian tissue were detected by real-time fluorescence quantitative PCR and Western blot.@*RESULTS@#Compared with the blank group, the level of ROS and the expression of JNK mRNA, p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the model group were increased (P<0.01). Compared with the model group, the level of ROS and the expression of p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the sham acupuncture group were slightly reduced, but the difference was not statistically significant (P>0.05). The level of ROS and the expression of JNK mRNA, p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the acupuncture group and the medication group were reduced (P<0.01).@*CONCLUSION@#Acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) could improve the level of oxidative stress, down-regulate the expression of apoptosis-related factors JNK, FoxO1, p53 and Puma induced by oxidative stress, and inhibit the premature failure of ovarian reserve function caused by apoptosis of ovarian granulosa cells in POI rats.

Efficacy and safety of rituximab in children and adolescents with mature B-cell non-Hodgkin's lymphoma: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis.@*METHODS@#The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis.@*RESULTS@#The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24).@*CONCLUSIONS@#The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.

Clinical features and prognosis of children with Burkitt's lymphoma: an analysis of 62 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and chemotherapy response of Burkitt's lymphoma (BL) in children and the influence of rituximab on the prognosis of children with BL.@*METHODS@#A retrospective analysis was performed for the medical data of 62 children with BL, including clinical features, therapeutic efficacy, and prognostic factors. The Cox regression model was used to identify the factors associated with poor prognosis in children with BL. According to whether rituximab was used, the children with advanced (stage III/IV) BL were divided into two groups: chemotherapy plus rituximab and chemotherapy alone. The prognosis was compared between the two groups.@*RESULTS@#For these 62 children, the median age of onset was 5 years (range 1-14 years), and there were 58 boys (94%) and 4 girls (6%). The primary site was abdominal cavity in 41 children (66%), and head and neck in 16 children (26%). There were 1 child with stage I BL (2%), 8 with stage II BL (13%), 33 with stage III BL (53%), and 20 with stage IV BL (32%). The median follow-up time was 29 months, with progression/recurrence observed in 15 children (24%), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±5.2% and 77.3%±5.8%, respectively. For the children with stage III/IV BL, there was a significant difference in the 3-year the OS rate between the chemotherapy plus rituximab group (16 children) and the chemotherapy alone group (30 children) (93.3%±6.4% vs 65.6%±9.9%, P=0.042), while there was no significant difference in the 3-year EFS rate between the two groups (86.2%±9.1% vs 61.8%±10.1%, P>0.05). The Cox regression analysis showed that central nervous system involvement, lactate dehydrogenase >1 000 U/L, and early incomplete remission were the factors associated with poor prognosis (P<0.05).@*CONCLUSIONS@#Chemotherapy combined with rituximab can improve the prognosis of children with stage III/IV BL. Central nervous system involvement, elevated lactate dehydrogenase level, and early incomplete remission may indicate a poor prognosis in children with BL.

Effects of total flavonoids of Rhododendra simsii on ameliorating brain injury via G protein-coupled SOCE pathway mediated by STIM and Orai in subacute phase of ischemia/reperfusion / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect of total flavonoids of Rhododendra simsii (TFR) on improving cerebral ischemia/reperfusion injury (CIRI) and its relationship with STIM/Orai-regulated operational Ca2+influx (SOCE) pathway. METHODS Oxygen-glucose deprivation/reoxygenation (OGD/R) PC12 cells were used to simulate CIRI in vitro, and the intracellular Ca2+ concentration and apoptosis rate of PC12 cells were detected by laser confocal microscope and flow cytometry, respectively. The regulation of STIM/Orai on SOCE was analyzed by STIM/Orai gene silencing and STIM/Orai gene overexpression. The CIRI model was established by MCAO in SD rats. The activities of inflammatory cyto?kines IL-1, IL-6 and TNF-αin serum were detected by ELISA. The pathological changes of ischemic brain tissue and the infarction of rat brain tissue were detected by HE staining and TTC staining. The protein and mRNA expression levels of STIM1, STIM2, Orai1, caspase-3 and PKB in brain tissue were detected by Western blotting and RT-qPCR, respectively. RESULTS The results of in vitro experiment showed that the fluorescence intensity of Ca2+ and apoptosis rate in PC12 cells treated with TFR were significantly lower than those in OGD/R group, and this trend was enhanced by SOCE antagonist 2-APB. STIM1/STIM2/Orai1 gene silencing significantly reduced apoptosis and Ca2+overload in OGD/R model, while TFR combined with overexpression of STIM1/STIM2/Orai1 aggravated apoptosis and Ca2+overload. In the in vivo experiment, TFR significantly reduced the brain histopathological damage, infarction of brain tissue, the contents of IL-1, IL-6 and TNF-α in the serum in MCAO rats and down-regulated the expression of STIM1, STIM2, Orai1 and caspase-3 protein and mRNA in the brain tissue, and up-regulated the expression of PKB. The above effects were enhanced by the addition of 2-APB. CONCLUSION The above results indicate that TFR may reduce the contents of inflammatory factors and apoptosis, decrease Ca2+ overload and ameliorate brain injury by inhibiting SOCE pathway mediated by STIM and Orai, suggesting that it has a protective effect against subacute CIRI.

Langerhans cell histiocytosis involving the oral and maxillofacial region: an analysis of 12 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of Langerhans cell histiocytosis (LCH) involving the oral and maxillofacial region in children.@*METHODS@#A retrospective analysis was performed for the clinical data of 12 children with LCH involving the oral and maxillofacial region who were hospitalized and treated from September 2012 to September 2017, including clinical manifestations, pathological features, treatment and prognosis.@*RESULTS@#Of the 12 children, 8 (67%) had multiple system involvement and 7 (58%) had the involvement of organs at risk. Bone was the most common affected site (11 children, 92%), among whom 7 children had the involvement of the mandible. Oral soft tissue involvement manifested as gingival ulcer or hyperplasia in 4 children, loose teeth in 5 children, oral mucosal lesions in 2 children, and nodular lesions in 1 child. Pathological examination showed positive CDla in 11 children and positive CD207, CD68, S-100, and LCA in 12 children. Surgery combined with chemotherapy was the major treatment method, and surgical resection alone was performed for focal lesions. After treatment, 11 children were cured or improved and 1 gave up treatment and was lost to follow-up. No recurrence was observed.@*CONCLUSIONS@#LCH children with oral and maxillofacial involvement often have the involvement of multiple systems and organs at risk, with the mandible as the most common affected site. These children may also have the involvement of gingiva, oral mucosa and teeth. Surgery combined with chemotherapy is the major treatment method, and the patients generally have a good prognosis without recurrence.

Nondestructive Assessment of Glycosaminoglycans in Engineered Cartilages Using Hexabrix-Enhanced Micro-Computed Tomography

It is very useful to evaluate the content and 3D distribution of extracellular matrix non-destructively in tissue engineering. This study evaluated the feasibility of using micro-computed tomography (µCT) with Hexabrix to measure quantitatively sulfated glycosaminoglycans (GAGs) of engineered cartilage. Rabbit chondrocytes at passage 2 were used to produce artificial cartilages in polyglycolic acid scaffolds in vitro. Engineered cartilages were incubated with Hexabrix 320 for 20 min and analyzed via µCT scanning. The number of voxels in the 2D and 3D scanning images were counted to estimate the amount of sulfated GAGs. The optimal threshold value for quantification was determined by regression analysis. The 2D µCT images of an engineered cartilage showed positive correlation with the histological image of Safranin-O staining. Quantitative data obtained with the 3D µCT images of 14 engineered cartilages showed strong correlation with sulfated GAGs contents obtained by biochemical analysis (R² = 0.883, p < 0.001). Repeated exposure of engineered cartilages to Hexabrix 320 and µCT scanning did not significantly affect cell viability, total DNA content, or the total content of sulfated GAGs. We conclude that µCT imaging using Hexabrix 320 provides high spatial resolution and sensitivity to assess the content and 3D distribution of sulfated GAGs in engineered cartilages. It is expected to be a valuable tool to evaluate the quality of engineered cartilage for commercial development in the future.

Expression of PI3-K, PKB and GSK-3 β in the skeletal muscle tissue of gestational diabetes mellitus

OBJECTIVE@#To analyze the expression of phosphatidylinositol 3 kinase (PI3-K), protein kinase B (PKB) and glycogen synthase kinase 3 beta (GSK-3 β) in skeletal muscle tissue of gestational diabetes mellitus (GDM).@*METHODS@#A total of 90 cases of pregnant women were divided into observation group and control group according to the occurrence of GDM with 45 cases in either, and the expression of PI3-K, PKB, GSK-3 β mRNA expression in skeletal muscle tissue was compared between two groups.@*RESULTS@#The total PI3-K p85 protein was significantly higher in the observation group compared with the control group, the activity of PI3-K was lower than that of the latter; The total PKB, GSK-3 β protein in skeletal tissue had no significant difference between two groups, while the serine phosphorylation levels of PKB and GSK-3β were significantly lower in observation group compared with the control group.@*CONCLUSIONS@#The downregulation of PI3-K, PKB and GSK-3βin skeletal tissue of GDM caused by phosphorylation dysfunction of signaling molecules is the reason for insulin resistance and transporter function decline which lead to GDM.

Effect of electro-acupuncture on clinical outcomes and ovarian hyperstimulation syndrome in in vitro fertilization and embryo transplantation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of electro-acupuncture (EA) on clinical outcomes and the occurrence of ovarian hyperstimulation syndrome (OHSS) in in vitro fertilization and embryo transplantation.</p><p><b>METHODS</b>Totally 109 patients who routinely received in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at Reproductive Center were assigned to the control group (56 cases) and the EA group (53 cases) according to even and odd-numbered date. Patients in the control group received controlled ovarian hyperstimulation (COH) referring to GnRH-a long protocol. On the basis of COH, those in the EA group received EA from the day of Gn injection to the day of embryo transfer. Estradiol (E2), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and angiotensin (AT) II were measured in all patients on the day of hCG injection, the day of ovum pick up (OPU), and the day of embryo transfer (ET), respectively. The oocyte retrieval rate, good quality embryo rate, clinical pregnancy rate, the abortion rate, and the occurrence of OHSS were compared between the two groups.</p><p><b>RESULTS</b>Compared with the control group, serum E2 levels on the day of OPU and the day of ET were significantly lower in the EA group (P < 0.05). On the day of OPU levels of VEGF and IL-6 also significantly decreased (P < 0.05). Serum levels of VEGF and IL-6 reached the highest line on the day of hCG in the two groups, and then showed a decreasing trend. Compared with the control group at the same time point, serum levels of VEGF and IL-6 obviously decreased on on the day of OPU, hCG, and ET (P < 0.05). The occurrence of OHSS and the canceling rate of transplant cycle were significantly lower in the EA group than in the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>EA, as an adjunctive therapy, could reduce the occurrence of OHSS in IVF. Besides, it did not decrease good embryo rates and pregnancy rates in IVF-ET, which might be associated with lowering local vascular permeability of ovaries.</p>

Performance of the CKD-EPI creatinine-cystatin C glomerular filtration rate estimation equations in a multiethnic Asian population

<p><b>INTRODUCTION</b>Clinical practice guidelines recommend using creatinine-based equations to estimate glomerular filtration rates (GFRs). While these equations were formulated for Caucasian-American populations and have adjustment coefficients for African-American populations, they are not validated for other ethnicities. The Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) recently developed a new equation that uses both creatinine and cystatin C. We aimed to assess the accuracy of this equation in estimating the GFRs of participants (healthy and with chronic kidney disease [CKD]) from a multiethnic Asian population.</p><p><b>METHODS</b>Serum samples from the Asian Kidney Disease Study and the Singapore Kidney Function Study were used. GFR was measured using plasma clearance of 99mTc-DTPA. GFR was estimated using the CKD-EPI equations. The performance of GFR estimation equations were examined using median and interquartile range values, and the percentage difference from the measured GFR.</p><p><b>RESULTS</b>The study comprised 335 participants (69.3% with CKD; 38.5% Chinese, 29.6% Malays, 23.6% Indians, 8.3% others), with a mean age of 53.5 ± 15.1 years. Mean standardised serum creatinine was 127 ± 86 μmol/L, while mean standardised serum cystatin C and mean measured GFR were 1.43 ± 0.74 mg/L and 67 ± 33 mL/min/1.73 m2, respectively. The creatinine-cystatin C CKD-EPI equation performed the best, with an estimated GFR of 67 ± 35 mL/min/1.73 m2.</p><p><b>CONCLUSION</b>The new creatinine-cystatin C equation estimated GFR with little bias, and had increased precision and accuracy in our multiethnic Asian population. This two-biomarker equation may increase the accuracy of population studies on CKD, without the need to consider ethnicity.</p>

Sorting,identification and enrichment of side population cells in acute monocytic leukemia THP-1 Cells / 中华实用儿科临床杂志

Objective To assay and determine whether the human acute monocytic leukemia cell line THP-1 contains side populations (SP) cells,and to increase the proportion of SP cells using cytarabine (Ara-C).Methods Fluorescent microscope and flow cytometry (FCM) were employed for detecting the percentage of SP cells in THP-1 cells.Then,SP and non-SP (NSP) subpopulations were collected and identified.Finally,THP-1 cells were incubated with different concentrations of Ara-C for 24 hours and detected the proportion of SP cells,respectively.Results The results demonstrated that the percentage of SP cells was (1.81 ± 0.99) ％ in THP-1 cells.A majority of the SP cells remained in the G0/G1 phase,and the expressions of CD34 + and CD34 + CD38-and the proliferative ability of the SP cells were higher than those of NSP cells (P ＜ 0.05).The mRNA expression of multidrug resistance genes (ABCG2,ABCB1),apoptosis regulation genes (Bcl-2) and the Bcl-2/Bax ratio of SP cells were higher than those of NSP cells.SP cells have been shown to be more tumorigenic than NSP cells.After co-culture with Ara-C,the proportion of SP cells increased significantly and presented in a concentration-dependent manor.Conclusions All of these findings suggest that the THP-1 cell line contains SP cells and the SP cells possess some intrinsic stem cell properties.The proportion of SP cells can be increased when co-cultured with Ara C,and this technique is a useful and important application for the study of LSCs.

Role of alcohol-metabolizing enzymes gene polymorphisms and environmental exposure on colorectal cancer: a case-only study / 中华流行病学杂志

<p><b>OBJECTIVE</b>This study was designed to explore the interactions of alcohol dehydrogenase 1B (ADH1B) rs1229984, aldehyde dehydrogenase 2 (ALDH2)(rs671) and cytochrome P4502E1(CYP2E1)rs1329149 with environmental factors and the interactions between genetic factors in the susceptibility of colorectal cancer (CRC). Roles of genetic factors in the development of colorectal cancer were also studied.</p><p><b>METHODS</b>With a case-only study design, 472 colorectal cancer cases were enrolled between 2007 and 2009 in this study. Data on demographic characteristics, histories of environmental exposure and clinico-pathological parameters were obtained from all the participants through written questionnaires. Genotypes were determined by Sequenom MassARRAY system. Unconditional logistic regression analysis was employed to explore the gene-environment interactions and gene-gene interactions. χ(2) test and unconditional logistic regression were used to evaluate the roles of polymorphisms on the risk of metastasis to CRC.</p><p><b>RESULTS</b>Overweighted individuals that carrying at least one of the ADH1B rs1229984 G alleles presented significant increase on the risk to colorectal cancer(OR = 1.720, 95%CI:1.038-2.848,ORadj = 1.785, 95%CI:1.061-3.002). Modest interaction was seen between smoking and ADH1B(rs1229984) only before the adjustment of data, by sex, age and drinking status(OR = 0.597, 95% CI:0.387-0.921, ORadj = 0.922, 95%CI:0.509-1.669). Correlations between polymorphisms and the Dukes stage were not found.</p><p><b>CONCLUSION</b>Overweight presented significant interaction with G allele of ADH1B rs1229984 in the susceptibility of CRC. None of the rs1229984, rs671 and rs1329149 exhibited significant influence on the development of CRC.</p>

Effectiveness of anti-CD47 antibody and Ara-C combination targeting therapy NOD/SCID mouse of myeloid leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the prognostic significance of CD47 in a NOD/SCID mouse model of acute myeloid leukemia (AML) and the best strategy for targeted therapy for this disease.</p><p><b>METHODS</b>CD34(+)CD38(-) leukemia stem cells (LSCs) were separated and transplanted into NOD/SCID mice to establish a mouse model of acute monocytic leukemia (AMoL). Anti-human CD47 antibody, alone or combined with cytosine arabinoside (Ara-C), was used to treat the mice with AMoL for 7-14 days, and therapeutic efficacy was assessed. LSCs were cultured together with mouse macrophages in culture medium containing anti-CD47 or anti-CD45 monoclonal antibody for 2 hours, to observe the phagocytic ability of macrophages to LSCs.</p><p><b>RESULTS</b>CD34(+)CD38(-) LSCs existed among THP-1 cells, with a content of about (0.12 ± 0.06)%, and a mouse model of AML was successfully established after the purified CD34(+)CD38(-) LSCs (97.0% ± 1.7%) were transplanted into NOD/SCID mice. The in vivo experiment showed that mice with AMoL had the most significant decrease in CD33(+)CD45(+) leukemia cells in peripheral blood and bone marrow and survived the longest after being treated with Ara-C (7 days) plus anti-CD47 monoclonal antibody (14 days) (P < 0.01). After 2 hours of in vitro culture, the phagocytic index in the culture medium containing anti-CD47 monoclonal antibody was significantly higher than in the culture medium containing anti-CD45 monoclonal antibody (76.9% ± 12.2% vs 7.60% ± 2.4%; P < 0.05).</p><p><b>CONCLUSIONS</b>High expression of CD47 is an adverse prognostic factor in AML. Combination therapy with anti-CD47 monoclonal antibody and Ara-C can effectively eliminate leukemia cells and LSCs, demonstrating great clinical significance in curing AML.</p>

The characteristics of vascular endothelial injuries induced by extreme environmental factors / 中国应用生理学杂志

Vascular endothelium plays an important role in regulating vascular homeostasis. Over the past years, it has become clear that endothelial dysfunction is a key event of pathophysiological changes in the initiation and progression of injuries induced by extreme environmental factors. The present review summarizes current understanding of vascular endothelial dysfunction induced by hypoxia, cold and heat, and provides the information for prevention and treatment of environmental exposure injuries.

The acclimatization to extreme environments and its physiological mechanisms / 中国应用生理学杂志

Acclimatization is a process of biological adaptation when exposed to environmental factors such as hypoxia, cold and heat for prolonged periods of time, where non-genetical variations play a role in allowing subjects to tolerate hypoxic, cold or hot environments. This review focuses on the characteristics and mechanisms of acclimatization found through major research advances by our institute. First, the mechanisms underlying the acclimatization to extreme environments are complex. In our investigations, the physiological changes of multiple systems including the nervous, circulatory, respiratory, and hemopoietic system were demonstrated when the acclimatization to hypoxia was developed, and the underlying significance of hypoxia-inducible factor-1 (HIF-1) was investigated. Second, it is suggested that the development of acclimatization to extreme environments is complicated. Hypoxia and cold coexist at high altitude. Our investigations revealed the characteristics of negative cross-relationship in the acclimatization to hypoxia and cold. And third, it is interesting for us to understand that acclimatization to extreme environments is transferable among individuals, and the characteristics of heat acclimatization-inducing factor (HAlF) were presented. The above findings will provide a theoretical guidance for protective operations and help to establish a solid foundation for future research related to acclimatization.

Efficacy of immunosuppressive therapy for children with aplastic anemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effectiveness and safety of immunosuppressive therapy (IST) in the treatment of childhood aplastic anemia (AA) and to study the main factors influencing the effectiveness.</p><p><b>METHODS</b>The clinical data of 55 children with severe aplastic anemia (SAA) and 51 children with chronic aplastic anemia (CAA) were retrospectively analyzed. All patients received IST from January 2007 to December 2010.</p><p><b>RESULTS</b>In children with CAA, the effective rate of antithymocyte globulin (ATG) plus cyclosporine A(CsA) combination therapy was significantly higher than that of CsA alone (80% vs 44%; P<0.05); in children with SAA, the effective rate of ATG plus CsA combination therapy was also significantly higher than that of CsA alone (75% vs 40%; P<0.05). No patients developed clonal disease such as myelodysplastic syndrome, paroxysmal nocturn hemoglobinuria or acute myelocytic leukemia. In patients treated with the ATG plus CsA combination therapy, the response rate was relatively high for children whose disease course was less than six months, bone marrow hematopoietic area was more than 40%, had no severe infections, and experienced granulocyte colony stimulating factor (G-CSF) reaction during the early treatment; however, it was not related to AA subtypes and age.</p><p><b>CONCLUSIONS</b>ATG plus CsA combination therapy is effective and safe in the treatment of childhood AA. The disease course, bone marrow hematopoietic area, severe infections and G-CSF reaction to early treatment are the main factors influencing the therapeutic effects.</p>

Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.</p><p><b>METHODS</b>This 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.</p><p><b>RESULTS</b>A total of 1447 children with ADHD (mean age (9.52 ± 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 ± 2.71) versus the score at baseline (10.45 ± 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study.</p><p><b>CONCLUSION</b>This open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.</p>

Expression of estrogen receptor alpha in the testis of infertile men with spermatogenic arrest / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the association of spermatogenic arrest with the expression of estrogen receptor alpha (ERalpha) in human testes.</p><p><b>METHODS</b>We examined the testicular biopsy specimens of 120 infertile men by HE staining, detected the expression of ERalpha in the specimens of those with spermatogenic arrest by the two-step immunohistochemical method, and compared the results with those of 10 healthy men.</p><p><b>RESULTS</b>Of the 120 specimens from the infertile men, 31 (25.8%) met the diagnostic criteria of spermatogenic arrest. In the testis tissue of normal men, ERalpha expressed in Sertoli, myoid and Leydig cells, but not in spermatogenic cells, while in the testis tissues of those with spermatogenic arrest, ERalpha expressed lowly in Sertoli, myoid and Leydig cells, with statistically significant differences in immunostaining intensity between the two groups (P < 0.05).</p><p><b>CONCLUSION</b>Androgen receptor (AR) and ERalpha may play a coordinating role in facilitating spermatogenesis. Spermatogenic arrest may be related to a complex series of disorders in cell signal transduction involving AR, ERalpha and HSP90.</p>