Analysis on the influencing factors for re-positive nucleic acid test result in discharged COVID-19 patients in Chengdu / 中国胸心血管外科临床杂志

@#Objective    To analyze the influencing factors for re-positive nucleic acid test in discharged corona-virus disease 2019 (COVID-19) patients in Chengdu, Sichuan Province, and to provide data support for the epidemics prevention and control. Methods    The clinical data of 660 discharged COVID-19 patients from January 23, 2020 to February 28, 2021 in our center were retrospectively analyzed. The patients were divided into two groups according to the reexamination of virus nucleic acid, including a negative group [549 patients, including 428 males and 121 females with a median age of 33.0 (28.0, 48.0) years] and a positive group [111 patients, including 76 males and 35 females with a median age of 39.0 (28.0, 51.0) years]. The clinical data of the two groups were compared. Results     The re-positive rate of the discharged patients was 16.82%. Univariate analysis showed that the re-positive rate of females was higher than that of males (χ2=4.608, P=0.032). The re-positive rate of confirmed patients was higher than that of asymptomatic infected patients (χ2=8.140, P=0.004). The re-positive rate of domestic patients was higher than that of imported patients (χ2=9.178, P=0.002). The counts of CD3+ (P=0.038), CD4+ (P=0.048) and CD8+ (P=0.040) T lymphocytes in the negative group were higher than those in the positive group. The binary logistic regression analysis showed that the clinical classification and CD8+ T lymphocyte count were independent risk factors affecting the recurrence of virility. Conclusion    The gender, origin, T lymphocyte subsets count and clinical type are the influencing factors for re-positive result, and clinical type and CD8+ T lymphocyte count are the independent influencing factors for re-positive result. Therefore, improving the immunity of infected patients, as well as early detection and timely treatment are effective means to reduce the re-positive occurrence.

Sesquiterpenoids from the leaves of Sarcandra glabra / 中国天然药物

Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC50 values at 20.00 ± 1.30 μmol·L-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.

Analysis on the imported Coronavirus Disease 2019 related cluster epidemic in rural areas of Chengdu / 中华预防医学杂志

An epidemiological investigation was carried out on a local cluster of outbreak caused by imported cases of Coronavirus Disease 2019 (COVID-19) in rural areas of Chengdu in December 2020, to find out the source of infection and the chain of transmission. According to

Associations of Hand-Foot-Mouth disease incidence among children of different age groups in kindergartens / 中国学校卫生

Objective@#To explore the associations of Hand-Foot-Mouth disease (HFM) among children of different age groups in kindergartens, and to provide scientific evidence for HFM prevention and control.@*Methods@#Cluster sampling was used to select 9 912 children from 40 kindergartens. The major caregivers of children were invited to participate into the study and fulfill a self-administered questionnaire that consisted of general background, hand washing and the history of HFM among children in the recent 1 year. Chi-square and binary logistic regression were applied,to analyze the influencing factors of HFM among children of different age groups.@*Results@#In the 2 year-old-group, children who were male (OR=1.76, 95%CI=1.24-2.50), had the major caregiver with high school educational background or below (OR=1.54, 95%CI=1.06-2.24), had family income more than 100 000 yuan or more per year(OR=1.49, 95%CI=1.01-2.20), children whose major caregiver seldom wash hands immediately after coming home(OR=2.10, 95%CI=1.05-4.19)，and 3-5 times per week(OR=2.07, 95%CI=1.26-3.41) were more likely to have HFM. In the 3 year-old-group, the more time children spent in the outdoors, the less likely they got HFM(3-5 times per week: OR=0.58, 95%CI=0.43-0.81; ≥6 times per week: OR=0.45, 95%CI=0.29-0.70). Children whose major caregiver did not use soap were more likely to have HFM(OR=1.67, 95%CI=1.11-2.49). In the 4 year-old-group, children who occasionally took toys when going out were less likely to get HFM (vs always, OR=0.57, 95%CI=0.38-0.88). No significant factors were found in the 5 year-old-group.@*Conclusion@#The behaviors and activities of major caregivers and children could influence the HFM incidence.To prevent HFM, it was advised that the major caregivers should wash hands immediately after coming home, and develop the habit of using soap for handwashing together with children at the earlier age, and encourage children to take more outside-door activities according to the age characteristics. Attention should be paid to avoid contaminating takeout snacks, and to clean the takeout toys timely.

Analysis of Medical Cases of Coronavirus Disease-2019 Treated with Haoqin Qingdantang / 中国实验方剂学杂志

Coronavirus disease-2019 (COVID-19) is highly contagious. In the early stages of the disease, the symptoms of coldness, dampness and depression in the lungs often appear, including fever, fatigue, soreness, dry cough, poor appetite, and white greasy tongue coating. During the development of the disease, the damp toxin epidemic often enters the inner and generates heat, and the damp heat epidemic toxin blocks pleurodiaphragmatic sites, the triple energizer and lungs, with manifestations of chest tightness, shortness of breath, exacerbation after exercise, or high fever without bringing down, poor appetite, bitterness in mouth, fatigue, diarrhea, loose stools, and yellow and thick tongue fur. As the pathogen can go outward or enter more deeply inside to cause death at the moment, it is the crucial time to treat the disease. In this study, Haoqin Qingdantang was used to clear dampness and heat, reconcile Shaoyang channel and recover the triple energizer, detoxify the dampness fever epidemic toxin, and block the toxin inside, with a good efficacy. This prescription focuses on smoothing the Shaoyang gallbladder channel and the triple energizer, and regards the spleen and stomach as the acquired essence. In the prescription, Erchentang reconciles the spleen and stomach, elevates clear Qi and lower turbid Qi. Bupleuri Radix is added to increase its detoxification function, and Paeoniae Rubra Radix is added to circulate the blood and prevent pathogen from the blood. When the condition improves, Sweet Wormwood Herb and talc are often withdrawn, and Codonopsis is added to nourish the spleen and stomach, to strengthening vital qi to eliminate pathogenic factor. Based on the cases of COVID-19 treated in Wuhan Jinyintan Hospital, this paper summarized some experience of applying Haoqin Qingdantang.

Effects of Yiqi Huayu Hutan decoction on pulmonary fibrosis in rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of Yiqi Huayu Hutan decoction on pulmonary fibrosis of rats which induced by bleomycin.@*METHODS@#The rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin hydrochloride (5 mg/kg). Sixty SD rats were randomly divided into the normal group (group N), the model group (group M), the positive control group (group Y), group of low concentration (group LC), group of medium concentration (group MC) and group of high concentration of Yiqi Huayu Hutan decoction (group HC). After 4 weeks, the experimental groups were treated with low concentration decoction, medium concentration decoction and high concentration decoction respectively, and the Y group was treated with hydrocortisone acetate, the Group N and group M were treated with saline by intragastric administration. Twelve weeks later, rats were killed and the pathomorphism of pulmonary tissues of each group was observed by HE staining and Masson staining. Further, the expressions of transforming growth factor-β1(TGF-β1), Snail1, E-cadherin and Fibronectin in pulmonary tissues of each group were detected by qTR-PCR and Western blot.@*RESULTS@#Compared with the model group, the collagen sediment in the interstitial was reduced in the experimental groups, especially in the group of medium concentration, which was observed by HE staining and Masson staining .Compared with the model group, the expressions of TGF-β1, Snail1 and Fibronectin protein in pulmonary tissues of the treatment groups were decreased in the experimental group, especially in the group of medium concentration, which were detected by qRT-PCR and Western blot.@*CONCLUSION@#Yiqi Huayu Hutan decoction can significantly improve the pulmonary fibrosis which is induced by bleomycin, and the mechanism is related to the inhibition of the expression of TGF-β/Snail pathway of transcription TGF-β1.

Effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion induced myocardial injury in mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice.@*METHODS@#Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot.@*RESULTS@#Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA.@*CONCLUSIONS@#The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.

Effect of dexmedetomidine on apoptosis and CHOP in hypoxia/reoxygenation injury A549 cell / 中国应用生理学杂志

OBJECTIVES@#To investigate the effects of dexmedetomidine (Dex) on injury of A549 cells induced by hypoxia/reoxygenation(H/R)and the influence of C/EBP homologous protein (CHOP) expression.@*METHODS@#Logarithmic growth phase A549 cells(it originated from alveolar type Ⅱ epithelial cell line) were randomly divided into 4 groups (=10):normoxic control group (N), Dex group (D), hypoxia/reoxygenation group (H), hypoxia/reoxygenation + Dex group(HD). At the beginning of modeling, 1 nmol/L Dex was puted into D and HD groups. N and D groups were cultured in the normoxic incubator for 30 h. H and HD group were incubated in the anoxic cultivation for 6 h, fo llowed by normoxic culture for 24 h. Then A549 cells were observed under the inverted microscope to observe the morphological changes. Cell activity was detected by cell counting Kit-8(CCK-8) and the apoptosis index(AI) was detected by in situ end labeling (TUNEL) method. The expression of CHOP、glucose-regulated protein of molecular weight 78 kDa (Grp78)、cysteinyl aspirate-specificprotease-3 (caspase-3) protein and CHOP、Grp78 mRNA were detected by Western blot and RT-PCR.@*RESULTS@#Compared with N group, the number of adherent cells in H group decreased significantly, and cell morphology changed. The absorbance value in H group decreased obviously (<0. 01). The AI value and expression of CHOP, Grp78, caspase-3 proteins and CHOP, Grp78 mRNA were significantly increased (<0.01). Compared with H group, the cell damage in HD group was decreased, the absorbance value increased (<0.01), the number of apoptosis cells decreased relatively (<0.01), the expression of CHOP, caspase-3 protein and CHOP mRNA decreased (<0. 01).@*CONCLUSIONS@#Dex has notable effects against H/R injury, which may be related to effective inhibition of apoptosis mediated by the CHOP's signal path.

The effect of Yiqi Wenyang Huoxue Huatan Fang on hypoxia-hypercarbia induced pulmonary hypertension and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of Yiqi Wenyang Huoxue Huatan Fang (YWHHF) on alleviating hypoxia-hypercarbia pulmonary hypertension by inhibiting endothelial-mesenchymal transition (EndoMT) BMP-7/Smads pathway.@*METHODS@#Fifty male healthy SD rats of clean grede, weighting (180~220) g, were randomly divided into 5 groups (=10):normoxia group (N), hypoxia-hypercarbia group (HH); YWHHF high dose group (YH), middle dose group (YM) and low dose group (YL). The rats in N group were kept in normal oxygen environment, the remaining four groups were intermittently exposed to hypoxia-hypercarbia environment (9%~11% O, 5%~6% CO) for 4 weeks, 6 days a week, 8 hours per day. The rats in YH, YM, YL groups were received YWHHF gavage in a dosageof 0.6, 0.3, 0.15g/kg respectively (3 ml/kg),the rats in N and HH groups were received equal volume of normal saline. After 4 weeks, the mean pulmonary arterial pressure(mPAP) was detected,the right ventricular free wall and left ventricle plus ventricular septum were isolated to determine the right ventricular hypertrophy index. Lung ultrastructural changes were surveyed under an electronic microscopy, the changes of pulmonary artery structure surveyed by immunofluorescence, the mRNA levels of alpha-smooth muscle actin (α-SMA)、platelet endothelial cell adhesion molecule-1 (CD31)、bone morphogenetic protein-7 (BMP-7)、drosophila mothers against decapentaplegic protein1/5/8 (Smad1/5/8) were detected by RT-PCR, and the protein levels of α-SMA、CD31、BMP-7、p-Smad1/5/8 and Smad1/5/8 were detected by Western blot.@*RESULTS@#Compared with N group, mPAP and the right ventricular hypertrophy index were increased,some significant injuries also were discovered under microscopic observation,the mRNA and protein expression of α-SMA was increased, and the mRNA expressions of CD31、BMP-7、Smad1/5/8 were decreased in the other four groups, the protein expressions of CD31、BMP-7、p-Smad1/5/8 were decreased(<0.05). Compared with HH group, the above changes in YH、YM、YL groups were all improved (<0.05).@*CONCLUSIONS@#YWHHF can inhibit EndoMT to alleviate pulmonary hypertension, and the mechanism may be related to the promotion of the expression of BMP-7/Smads pathway.

Effect of Yiqi Huayu Huatan decoction on expression of KLF15, HMGB1,NF-κB and its downstream inflammatory factors in rats with UUO-induced renal interstitial fibrosis / 中国病理生理杂志

AIM:To observe the effect of Yiqi Huayu Huatan decoction(YHHD)on unilaterral ureteral ob-struction(UUO)-induced renal interstitial fibrosis in rats, and to investigate the possible mechanism.METHODS: Fe-male SD rats(n=48)were randomly divided into sham group, model group, telmisartan group, and low-, middle-and high-dose YHHD groups,with 8 rats in each group.The UUO model rats was established by ligating left ureter.The rats in sham group and model group were treated with equal volume of normal saline, others were treated with the corresponding drugs daily.After 12 weeks,the rats were sacrificed.The serum samples were collected for determining the concentrations of cystatin C(Cys-C)and uric acid(UA).The morphological changes of the renal tissue were observed by PAS staining. The collagen fiber was observed by Masson staining.The mRNA expression of Krüppel-like factor 15(KLF15),high-mo-bility group box protein 1(HMGB1),nuclear factor-κB(NF-κB),IκB,monocyte chemotactic protein-1(MCP-1),inter-leukin-1β(IL-1β), tumor necrosis factor-α(TNF-α),fibronectin(FN),collagen type I(Col I)and Col-Ⅳwas detec-ted by real-time PCR.The protein expression of KLF15, HMGB1 and NF-κB was detected by Western blot.The protein expression of MCP-1 was determined by the method of immunohistochemistry.RESULTS:Compared with sham group,the deposition rate of collagen fibers and the concentration of Cys-C in model group were significantly increased(P<0.05), the mRNA and protein expression of KLF15 was significantly down-regulated(P<0.05), while the mRNA expression of HMGB1,NF-κB,IκB,MCP-1,IL-1β,TNF-α,FN,Col I and Col Ⅳand the protein expression of HMGB1,NF-κB and MCP-1 were significantly up-regulated(P<0.05).Compared with model group,the deposition rates of collagen fibers in middle-and high-dose YHHD groups and telmisartan group were significantly decreased(P<0.05),with down-regulated protein expression of HMGB1 and NF-κB and mRNA expression of IL-1βand TNF-α(P<0.05).The protein expression of KLF15 was significantly up-regulated in high-dose YHHD group and telmisartan group(P<0.05),while the protein ex-pression of MCP-1 and the mRNA expression of FN were significantly down-regulated(P<0.05).The mRNA expression of KLF15 was significantly up-regulated in high-dose YHHD group(P<0.05), while the mRNA expression of MCP-1, Col I and Col IV was significantly down-regulated(P<0.05).The mRNA expression of NF-κB and IκB was significantly down-regulated and the concentration of Cys-C was significantly decreased in each dose of YHHD groups and telmisartan group(P<0.05).No significant difference of UA level among the groups was observed.CONCLUSION:YHHD allevi-ates renal interstitial fibrosis in a dose-dependent manner, and YHHD at high dose shows the most obvious effect.The mechanism may be associated with the up-regulation of KLF15 and the down-regulation of HMGB1, NF-κB and its down-stream inflammation-related factors in the renal tissue.

Role of EndoMT in HHPH based on TGF-β/Smads signaling pathway and regulated by Yiqi-Wenyang-Huoxue-Huatan formula / 中国病理生理杂志

AIM:To investigate the relationship between transforming growth factor-β(TGF-β)/Smads signa-ling pathway and pulmonary arterial endothelial-mesenchymal transition(EndoMT)in hypoxia-hypercapnia pulmonary hy-pertension(HHPH)process and the regulatory effect of Yiqi-Wenyang-Huoxue-Huatan formula(YWHHF).METHODS:Healthy male SD rats were randomly divided into 5 groups:normal control(N)group,hypoxia-hypercapnia(HH)group, high-dose YWHHF(YH)group,middle-dose YWHHF(YM)group and low-dose YWHHF(YL)group.The rats in N group was housed in normoxic environment,and the rats in the other 4 groups were housed in hypoxia-hypercapnia environ-ment(9%~11%O2and 5%~6%CO2)for 4 weeks,8 h/d,6 d/week.The excess water vapor was absorbed by anhy-drous CaCl2,and CO2was absorbed by sodium hydroxide.The rats in YWHHF groups were put into the oxygen chamber before the same volume of YWHHF at different concentrations were given(200 g/L for YH group,100 g/L for YM group and 50 g/L for YL group).The average pulmonary artery pressure and the average carotid artery pressure were measured during the operation.After operation,the right ventricular free wall and left ventricle plus interventricular septum were col -lected for determining the right ventricular hypertrophy index.Moreover,the morphological changes of the lung tissues were observed under light microscope.The mRNA and protein levels of α-smooth muscle actin(α-SMA),CD31,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were detected by RT-PCR and Western blot.RESULTS:Compared with N group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were increased, the levels of CD31 were decreased(P<0.05), and the lung tissue damage was observed in the other 4 groups.Compared with HH group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were decreased, while the mRNA and protein levels of CD31 were increased.Moreover,the lung tissue damage was reduced in YH,YM and YL groups.CON-CLUSION:TGF-β/Smads pathway may be involved in the process of EndoMT under hypoxia and hypercapnia condition, and YWHHF may reduce EndoMT by inhibiting the expression of TGF-β/Smads pathway-related molecules.

Excessive endoplasmic reticulum stress mediates brain damage in hypoxia hypercapnia induced pulmonary hypertension rats / 生理学报

The purpose of the present study was to investigate the effect of excessive endoplasmic reticulum stress (ERS) on the brain damage in hypoxia hypercapnia induced pulmonary hypertension (HHPH) rats. Forty healthy SPF male SD rats were randomly divided into four groups (n = 10 for each): control group, hypoxia hypercapnia group, ERS pathway agonist tunicamycin (TM) group and ERS pathway inhibitor 4-phenylbutyric acid (4-PBA) group. The rats of control group lived in normal environment, while the rats of other three groups were raised for four weeks in the tank with 8.5%-11% Oand 5%-6% CO. TM (0.08 mg/kg, twice a week) and 4-PBA (80 mg/kg, daily) were respectively intraperitoneally injected into the rats of TM and 4-PBA groups, and the hypoxia hypercapnia group was given the same volume of normal saline. The mean pulmonary artery pressure and heart perfusion of the rats were determined and recorded after four-week raising. Then the brain tissue of the rats were quickly taken out for the brain water content measuring and morphological changes observing. The Caspase-3 activity and the apoptotic index of the brain cells were also determined. The protein and mRNA expressions of p-JNK, Caspase-12, CHOP and GRP78 in brain tissues were detected by Western blot and RT-PCR. The results showed that compared with the control group, the mean pulmonary artery pressure, brain water content and brain cells apoptotic index, Caspase-3 activity, the protein and mRNA levels of p-JNK, Caspase-12, CHOP and GRP78 were increased (P < 0.05), and the brain tissues of the rats were obviously damaged in the rats raised in the hypoxia hypercapnia environment; compared with hypoxia hypercapnia group, the mean pulmonary artery pressure, brain water content, brain apoptotic index and Caspase-3 activity, p-JNK, Caspase-12, CHOP, GRP78 protein and mRNA expressions in TM group were increased (P < 0.05), and the brain tissues of the rats were obviously damaged, while all above changes were relieved in 4-PBA group (P < 0.05). These results suggest that excessive ERS may participate in the brain injury induced by HHPH in rats and inhibition of excessive ERS can relieve the brain injury in the rats with HHPH.

Investigation and analysis of the first cases of human infection with avian influenza A(H9N2) virus in Chengdu, China / 中国人兽共患病学报

We summarized the epidemiological investigation results of the first case of human infection with avian influenza A(H9N2) virus in Chengdu,China,in order to provide references for dealing with similar diseases scientifically in the future.The methods of field epidemiology and laboratory testing were used to collect the H9N2 case's clinical and epidemiological data,as well as collect and test the samples of the H9N2 case and the relevant environment,so that the possible sources of infection,the epidemiological characteristics and clinical features could be analyzed.Results showed that the H9N2 case contacted with poultry within 10 days before the onset of illness and the H9N2 virus nucleic acid was detected in the patient's specimen by PCR.This case suffered from several chronic diseases for a long time,although active treatments were taken this time,she died soon after onset.Her living environment,the chicken leftovers from cooking,and surrounding poultry markets were polluted by H9 avian influenza virus.Through the investigation,we could deduce that the infection source of this case was the chicken infecting H9N2 viruses from surrounding poultry markets.This would be the first fatality associated with influenza A (H9N2) virus infections in humans.And though avian influenza A(H9N2) virus was low pathogenic,infection could cause severe symptoms or death in people with severe underlying diseases.

Application of High-throughput Sequencing in Acute Myeloid Leukemia Patients with Positive FLT3-ITD / 中国实验血液学杂志

<p><b>UNLABELLED</b>OBJECTICE: To evaluate the application of high-throughput sequencing to sequence the FMS-like Tyrosine Kinase 3 internal tandem duplication (FLT3-ITD) in de novo acute myeloid leukemia (AML) patients with lower allelic ratio FLT3-ITD mutation or more than one ITD, and to analyze the feature of ITD.</p><p><b>METHODS</b>The genomic DNA of 23 AML patients with positive FLT3-ITD was amplified by PCR, capillary electrophoresis was used to detect the ITD mutation. Then, the FLT3 gene was amplified using primer with different barcode, and the product was analyzed by illumina Miseq, and the results were compared with UCSC database.</p><p><b>RESULTS</b>Out of 23 AML patients, 17 had a single ITD, and 3 had 2 ITDs, and the remaining 3 had 3 ITD detected by capillary electrophoresis. The high-throughput sequencing showed that 17 ITD were the complate duplications of wild-type FLT3, and the remaining 16 ITD were partial duplications in the all 33 ITDs. The same length ITD mutation contained 2 different ITD sequences in one patient with more than one ITD, and the other patient with 2 ITD had the same ITD insertion position. The ITD occurred in the regions from p. Y572 to p. L602 of the FLT3 protein, and all the patient ITD covered one or more amino acid between p. V592 and p. E598.</p><p><b>CONCLUSION</b>Illumina Miseq can analyze the sequence of ITDs precisely and accurately. ITD mutation varies widely, but the hotspots are concentrated.</p>

Minimally invasive screw and locking plate fixation for ankle fracture based on three-dimensional print model / 中国组织工程研究

BACKGROUND:Clinical physicians should pay attention on how to reduce ankle fracture healing wounds, reduce bleeding, improve operating technique, and improve repair effect, especialy for comminuted fracture. It is necessary to understand how to develop a detailed plan before repair, observe specific circumstances of the fracture from multiple angles, and establish three-dimensional images using two-dimensional X-ray films or CT scan. These raise a chalenge for each physician. OBJECTIVE:To explore the application effect of three-dimensional print, minimaly invasive percutaneous screw and locking plate fixation in the repair of ankle fractures. METHODS: A total of 26 cases of fracture of ankle joint were treated from January 2012 to June 2014. There were 9 cases of double ankle fracture, 12 cases of three ankle fractures, and 5 cases of three ankle fractures involved PILON fracture on the lower tibia. They received spiral CT scanning on the ankle joint, and stored in the format of di.com. After processing with minics software, data were converted into STL format, and then input into the three-dimensional printer. Thus, models of ankle joint were made at the ratio of 1:1. The repair scheme was made. After discharge, X-ray films were checked every month to observe the healing condition of fractures. According to Mazur ankle score standard, ankle joint function was assessed. RESULTS AND CONCLUSION: Al 26 cases were folowed up for 6-12 months. The fractures were healed. The healing time was 4-6 months, averagely 5.5 months. The healing was good, without vascular and nerve damage, or plate breakage. In accordance with the Mazur ankle score standard, there were excelent in 11 cases, good in 13 cases with an excelent and good rate of 92%. The operation time was (64±15) minutes, and intraoperative blood loss was (100±15) mL. The incision was healed in stage one. These findings confirm that the simulation training and operation in fracture models of three-dimensional print have smal injuries to patients with ankle fracture. The bleeding was less, the operation was simple, the healing time was short, and the functional recovery was rapid, especialy for comminuted fracture.

Progress on pharmacokinetic study of antibody-drug conjugates / 药学学报

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.

Autologous platelet-rich plasma and autologous bone graft for comminuted fractures：randomized controlled follow-up / 中国组织工程研究

BACKGROUND:Studies showed that platelet-rich plasma + bone transplantation for repair of bone defects not only can accelerate new bone formation, but also increase bone density. OBJECTIVE:To observe autologous platelet-rich plasma and autologous bone graft for treatment of comminuted fractures, and the efficacy. METHODS:This was a clinical prospective randomized controled study. A total of 42 patients with limb comminuted fracture and bone defects were enroled and randomly assigned to two groups. In the experimental group, 20 patients received treatment with autologous platelet-rich plasma and mixture of autologous ilium and cancelous bone. In the control group, 22 patients underwent plate, screw or intramedulary nail fixation. At 1, 3, 6 and 12 months after surgery, X-ray examination was conducted. Healing conditions, healing speed and functional recovery were compared between the experimental and control groups. RESULTS AND CONCLUSION:The time of bone healing was respectively 12 weeks in the experimental group and 18 weeks in the control group on average, showing significant differences. There were two cases of plate breakage, one case of nonunion reoperation, three cases of delayed fracture healing in the control group. No autologous blood transfusion or other complications appeared in the experimental group. Results suggested that autologous platelet-rich plasma and autologous bone graft for comminuted fractures can facilitate and accelerate bone healing.

CagA status and genetic characterization of metronidazole resistant strains of H. pylori from a region at high risk of gastric cancer

The aim of study was to determine relationship between cagA and genetic characterization of metronidazole [MTZ] resistant H. pylori strains from a region at high risk of gastric cancer. 172 H. pylori strains were isolated from the patients with dyspeptic symptoms, and antimicrobial susceptibility testing for MTZ was assessed by E-test. rdxA and frxA genes were amplified using PCR among the MTZ resistant isolates. The status of the plasmid and classes 1-3 integrons were investigated in all isolates. MTZ was detected in 88 isolates [51.16%]. Variations in the rdxA gene leading to alterations of amino acids in RdxA proteins were identified in all MTZ resistant strains. FrxA contained missense alterations in 55 MTZ resistant isolates, while the premature truncation of FrxA was caused by frameshift mutations in 9 MTZ resistant strains. Plasmid was found in one MTZ sensitive strain [0.58%], and none of Class 1-3 integrases gene was detected in the studied isolates. The conservative cagA fragment was obtained from all clinical isolates of H. pylori. The sequence of cagA 3' variable region in 164 strains were obtained, including East Asian-type [122, 74.39%] and Western-type [42, 25.61%]. Prevalence of Western-type cagA 3' variable region was significantly higher in MTZ resistant [33.73%, 28/83] than those of MTZ-sensitive strains [17.28%, 14/81] [p=0.02]. A high prevalence of MTZ resistance was found in the region, and bacterial chromosome mutations in the rdxA and frxA gene still contribute to the high-level MTZ resistance. H. pylori strains characterized with West-type cagA 3' variable region tend to acquire MTZ resistance in the region

Stability of simple suspension and twin-ring external fixation in the treatment of children clavicle fracture / 中国组织工程研究

BACKGROUND:Open reduction is general y not advocated for the treatment of children clavicle fracture, because the thick and tough periosteum remains intact and attached by the ligament attachment. In clinic, twin-ring external fixation and simple suspension are commonly used, but there is no reliable basis on which method can get better effect. OBJECTIVE:To compare the stability of twin-ring external fixation and simple suspension for the treatment of children clavicle fracture. METHODS:The patients with children clavicle fracture and treated by twin-ring external fixation and simple suspension were selected from June 2008 to December 2012, including 17 patients treated with simple suspension and 22 patients treated with twin-ring external fixation. The X-ray film examination was performed regularly to observe the fracture healing and shoulder function. RESULTS AND CONCLUSION:The 17 patients treated with simple suspension had good healing;three cases had gap between fracture ends at 1 week after treatment, and re-suspension to increase the height and final y two fracture ends contacted in one case;for the other two cases, there was stil gap between fracture ends, and changed for twin-ring external fixation, the fracture ends contacted. Al the 22 patients in the twin-ring external fixation group obtained healing;five cases had performance of upper extremity neurovascular compression on the fracture side after fixation;after releasing, three cases had recovery, and two cases were treated with simple suspension, the fracture ends began to contact;six cases had armpit redness;four cases had early sleep difficulties;two cases had gap between fracture ends at 1 week after treatment, and after re-adjust, the fracture ends contacted in two cases. The results showed both two methods could not cause appearance deformity, and both could get healing. The simple suspension fixation is easy to operate with reliable effect, and it is comfortable which make it easy to accept by the children, it has the advantages of early for functional exercise, less tissue damage, does not affect the blood supply;the twin-ring external fixation is easy to compress the axil ary arteries and nerves on both sides, thus resulting in upper extremity swel ing, numbness and skin redness, and it can cause discomfort night sleeping and poor comfort which is not easy for children to accept. But, no matter what method we take, the review after 1 week, as wel as the line between proximal and distal part and the contact between fracture ends is stil important.

Protective effects and mechanism of SP600125 on lung ischemia/reperfusion injury in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effects and mechanism of SP600125-specificity inhibitor of c-Jun N-terminal kinase (JNK)on lung ischemia /reperfusion injury in rats.</p><p><b>METHODS</b>The unilateral lung ischemia/reperfusion model was replicated in vivo. Rats were randomly divided into three groups (n = 10): control group, ischemia/reperfusion group ( I/R group) and ischemia/reperfusion + SP600125 group (SP600125 group). The lung tissues sampled at the end of each experiment were assayed for wet/dry weight ratio (W/D),the injured alveoli rate (IAR), the expression of phosphorylation JNK (p-JNK) and JNK protein were detected by Western blot, the expression of Bcl-2, Bax, Caspase3 protein were detected by immunocytochemistry techniques, the pneumocyte apoptosis index (AI) was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling(TUNEL), the ultrastructure changes were observed under electron microscope.</p><p><b>RESULTS</b>Compared to I/R group, the expression of p-JNK, Bcl-2, Bax and caspase-3 protein were markedly decreased (all P < 0.01), the expression of Bcl-2 protein and the ratio of Bcl-2/Bax were markedly increased in SP600125 group(all P < 0.01). The value of AI, W/D, IAR showed significantly lower than those in I/R group (all P <0.01). Meanwhile, light morphological and ultrastructure injury were found in SP600125 group.</p><p><b>CONCLUSION</b>SP600125 can suppress JNK signal pathway, up-regulate the ratio of Bcl-2/Bax to inhibit Caspase-3 dependent apoptosis, so that it protects lung tissue from ischemia/reperfusion injury.</p>