Advances of targeted protein degradation technology and its applications in diseases therapy / 生物工程学报

Targeted protein degradation (TPD) technology facilitates specific and efficient degradation of disease-related proteins through hijacking the two major protein degradation systems in mammalian cells: ubiquitin-proteasome system and lysosome pathway. Compared with traditional small molecule-inhibitors, TPD-based drugs exhibit the characteristics of a broader target spectrum. Compared with techniques interfere with protein expression on the gene and mRNA level, TPD-based drugs are target-specific, efficaciously rapid, and not constrained by post-translational modification of proteins. In the past 20 years, various TPD-based technologies have been developed. Most excitingly, two TPD-based therapeutic drugs have been approved by FDA for phase Ⅰ clinical trials in 2019. Despite of the early stage characteristics and various obstructions of the TPD technology, it could serve as a powerful tool for the development of novel drugs. This review summarizes the advances of different degradation systems based on TPD technologies and their applications in disease therapy. Moreover, the advantages and challenges of various technologies were discussed systematically, with the aim to provide theoretical guidance for further application of TPD technologies in scientific research and drug development.

Investigation of in-patient neonatal death at 18 hospitals in Henan Province / 中华围产医学杂志

Objective To investigate the situation and the causes of neonatal death in Henan Province.Methods This study retrospectively analyzed the clinical data of 277 neonates who died at 18 hospitals in Henan Province in 2017.Distribution and causes of neonatal deaths,differences between perinatal conditions of premature and term/post-term infants,causes of early (＜ 7 d) and late (7-28 d) neonatal deaths and the differences in neonatal death cases between Maternal and Child Health Care Hospitals and General/Children's Hospitals were analyzed.We used t,rank-sum and Chi-square test (or corrected Chi-square test,or Fisher's exact test) for statistical analysis.Results (1) A total of 50 993 newboms were admitted to the 18 hospitals in 2017,297 of which died with a mortality of 5.82‰.After excluding 20 cases with uncertain birth or maternal pregnancy history or clinical data,277 cases with complete data were analyzed.Among them,168 (60.6％) were preterm neonates and 109 (39.4％) were term/post-term ones.Early and late neonatal deaths accounted for 74.0％ (205 cases) and 26.0％ (72 cases),respectively.(2) The top five causes of neonatal deaths were infection (78 cases,28.2％),asphyxia (54 cases,19.5％),neonatal respiratory distress syndrome (NRDS,33 cases,11.9％),severe congenital malformations (26 cases,9.4％) including cyanotic congenital heart diseases,digestive malformations,airway malformations and neural tube defects and pulmonary hemorrhage (23 cases,8.3％).Among them,the top three causes of early neonatal deaths were asphyxia (48 cases,23.4％),infection (43 cases,21.0％) and NRDS (33 cases,16.1％),while the main causes of late neonatal deaths were infection (35 cases,48.6％),major congenital malformations (9 cases,12.5％) and chromosome abnormities/inherited metabolic diseases (7 cases,9.7％).(3) Maternal complications during pregnancy accounted for 79.1％ (219 cases) and the predominant types were pregnancy-induced hypertension (43 cases,19.6％),followed by infection (36 cases,16.4％),placental-related conditions (32 cases,14.6％),gestational diabetes mellitus (23 cases,10.5％),hypothyroidism (20 cases,9.1％),fetal distress (18,8.2％),twin-twin transfusion syndrome (10 cases,4.6％) and cholestasis syndrome (9 cases,4.1％).(4) Compared with the term/post-term cases,the preterm cases had higher proportions of multiple births [27.4％ (46/168) vs 6.4％ (9/109),x2=14.016,P ＜ 0.05],assisted reproduction [7.1％ (12/168) vs 0.9％ (1/109),x2=4.421,P ＜ 0.05] and maternal hypertensive disorders of pregnancy [21.4％ (36/1 68) vs 6.4％ (7/109),x2=11.353,P ＜ 0.05],infection [16.7％ (28/168) vs 7.3％ (8/109),x2=4.295,P ＜ 0.05] and twin-to-twin transfusion syndrome [6.0％ (10/168) vs 0.0％ (0/109),x2=6.707,P ＜ 0.05].(5) Among all the early neonatal deaths,preterm cases had a higher incidence of NRDS than term/post-term neonates [20.3％ (27/133) vs 8.3％ (6/72),x2=1 1.937,P ＜ 0.05],but lower incidence of meconium aspiration syndrome (MAS),severe congenital malformations and chromosome abnormalities/inherited metabolic diseases [0.8％ (1/133) vs 5.6％ (4/72),x2=4.508;3.8％ (5/133) vs 16.7％ (12/72),x2=10.233;1.5％ (2/133) vs 6.9％ (5/72),~=4.172;all P ＜ 0.05].Among the late neonatal deaths,the incidence of severe intracranial hemorrhage in preterm infants was higher than that in term/post-term neonates [7.1％ (3/42) vs 0.0％ (0/30),x2=2.205,P ＜ 0.05].(6) Compared with the cases in General/Children's Hospitals,those in Maternal and Child Health Care Hospitals showed a higher proportion of preterm neonatal deaths [67.3％ (105/156) vs 52.1％ (63/121),x2=6.010,P ＜ 0.05],younger gestational age [(32.8±5.3) weeks vs (34.6±4.9) weeks,t=3.072,P ＜ 0.05],lower birth weight [(2 132.6± 1 014.5) g vs (2 409.4±987.3) g,t=-2.513,P ＜ 0.05],and higher average age of death [M(P25-P75),3 (1-8) d vs 2 (1-4) d,Z=3.710,P ＜ 0.05].Conclusions Neonatal death occurs mainly within one week after birth in those with maternal complications.Late preterm deaths and term/post-term cases account for nearly half of total neonatal deaths.The causes of death for preterm and term/post-term newborns vary with postnatal age.Infection,asphyxia and severe congenital malformations are important causes of neonatal deaths.

Factors associated with intraoperative hypothermia in elderly patients and management strategies / 中华老年医学杂志

Objective To investigate the incidence of intraoperative hypothermia in elderly patients,and to analyze and discuss related influencing factors and targeted management strategies.Methods From February 2017 to February 2019,220 elderly patients admitted into our hospital for surgery were selected.According to whether or not they had intraoperative hypothermia,patients were divided into the hypothermia group and the non-hypothermia group.General information and surgical data were compared between the two groups.Measures for the prevention of intraoperative hypothermia were discussed.Results Of the 220 patients,103 had intraoperative hypothermia,and the incidence rate was 46.8％.The proportion of patients aged ≥70 years or with BMI ＜24 kg/m2 was higher in the hypothermia group than in the non-hypothermia group (all P ＜ 0.05).The proportion of patients with the anesthesia time ≥60 min or total intraoperative fluid intake ≥2000 ml was higher in the hypothermia group than in the non-hypothermia group(all P＜0.05).BMI ＜24 kg/m2 and total intraoperative fluid intake ≥ 2000 ml were the key risk factors for intraoperative hypothermia in elderly patients(all P＜0.05).Conclusions Intraoperative hypothermia is a common complication for elderly patients undergoing surgery.Intraoperative fluid intake and body mass are the key risk factors for intraoperative hypothermia.Targeted treatment measures based on the above related factors should be considered for elderly patients receiving surgery.

Effect of Nourishing Yin and Nonifying Yang Sequential Therapy Combined with Western Medicine on Expression Levels of Smad2 ,Smad3 ,Smad7 mRNA in Rats with Diminished Ovarian Reserve / 华中科技大学学报(医学版)

Objective To investigate the effect of Nourishing Yin and Nonifying Yang sequential therapy (NYNYST )com-bined with western medicine on expression levels of Smad2 ,Smad3 ,Smad7 mRNA in rats with diminished ovarian reserve (DOR).Methods Totally 40 female rats were randomly divided into 5 groups ,the normal control group ,the model group ,the western medicine group ,the NYNYST group and the combination group(western medicine combined with NYNYST ) ,8 in each group. The DOR model was established through orally administering tripterygium pill for continuous 2 weeks. The normal con-trol group and the model group were administered with saline for 10 days. The western medicine group was treated with hor-mone replacement therapy(HRT ) and ovarian stimulation. The NYNYST group was administered with Nourishing Yin herbs in proestrus and Nonifying Yang herbs in late estrus and the combination group was administered with combination of Chinese herb and western drugs for 10 days ,with the same dose in the former two groups.Serum levels of FSH ,LH ,E2 ,anti-Müllerian hormone(AMH) ,Transforming growth factor beta 1(TGF-β1)and Inhibin B(INHB)were measured by ELISA.Changes of Smad2 ,Smad3 ,Smad7 mRNA in ovaries were detected by real-time PCR.Results Compared with the model group ,the serum levels of FSH ,LH were decreased significantly in western medicine group ,NYNYST group and combination group(P＜0.01) , the serum levels of E2 ,AMH ,TGF-β1 and INHB increased in the rats of the treatment group(P＜0.05 ,P＜0.01) ,and efficacy of the combination group was significantly superior to that of the western medicine group (P＜0.01 ,P＜0.05);compared with the model group ,Smad2 mRNA increased significantly in NYNYST group and combination group ,Smad3 mRNA increased sig- nificantly in combination group(P＜0.01) ,the efficacy of combination group was superior to that of the western medicine group (P＜0.05);compared with the model group ,Smad7 mRNA of treatment groups was decreased significantly (P＜0.01).Conclu-sion NYTYST combined with western medicine can improve the function of ovaries by up-regulating the expression of Smad2 , Smad3 mRNA and down-regulating the expression of Smad7 mRNA in DOR rats.

Influence of nourishing yin and tonifying yang sequential therapy combined with Western medicine on TGF-β1/Smads signaling pathway in anovulatory infertility rats with diminished ovarian reserve / 中南大学学报(医学版)

To explore the influence for combination of nourishing yin and tonifying yang sequential therapy (NYTYST) with Western medicine in treating anovulatory infertility rats with diminished ovarian reserve (DOR) based on TGF-β1/Smads signaling pathway. 
 Methods: A total of 40 female rats were randomly divided into 5 groups, a normal control group, a model group, a Western medicine group, a NYTYST group and a combination group (n=8 in each group). The DOR model was established through orally taking tripterygium pill for continuous 2 weeks. The normal control group and the model group were treated with saline for 10 days. The Western medicine group was treated with hormone replacement therapy (HRT) and ovarian stimulation. The NYTYST group was treated with nourishing yin herbs in proestrus and tonifying yang herbs in late estrus and the combination group was treated with Chinese herb and Western drugs for 10 days. HE staining was used to observe histopathologic changes in ovary. Expression levels of transforming growth factor β1 receptor (TGF-β1R) in rats ovarian were detected by immunohistochemistry. Expression levels of Smad2, Smad3 and Smad7 protein in rat ovarian were detected by Western blot.
 Results: Compared with the control group, the numbers of developing follicles, mature follicles and corpus luteum were decreased , while atrefic follicles were increased significantly in the model group (P<0.01); the levels of TGF-β1R, Smad2 and Smad3 were decreased significantly, while Smad7 was increased significantly (P<0.01). Compared with the model group, the numbers of developing follicles, mature follicles and corpus luteum, Smad2 and Smad3 expression were increased, while atrefic follicles and Smad7 were decreased significantly in the treatment group (P<0.05 or P<0.01). The numbers of developing follicles and corpus luteum in the combination group was superior to the Western medicine group (P<0.05). Compared with the Western medicine group, the levels of TGF-β1R, Smad2 and Smad3 were increased significantly, while Smad7 was decreased significantly in the combination group (P<0.05 or P<0.01). 
 Conclusion: NYTYST combined with Western medicine can improve the function of ovaries reserve by up-regulation of TGF-β1R, Smad2 and Smad3 while down-regulation of Smad7 in DOR rats.

CARMA3 gene knockdown in HCT116 cells inhibits cell growth, migration and invasion / 中国病理生理杂志

AIM:To study the effcts of caspase recruitment domain membrane-associated guanylate kinase protein 3 (CARMA3) knockdown on the growth, migration and invasion of human colonic carcinoma HCT116 cells and to analyze the mechanism.METHODS:A colonic carcinoma cell line with CARMA3 over-expression was selected.The CARMA3 gene in the HCT116 cells was knocked down by lentivirus technique.After screening by puromycin, the stably-transfected HCT116-shCARMA3 cell line was constructed.CARMA3 expression at mRNA and protein levels was detected by real-time PCR and Western blot,respectively.The cell proliferation was analyzed by WST-1 assay and RTCA S16 system.The colony formation ability was measured by colony-forming assay.The cell cycle was analyzed by flow cytometry.The cell morphological changes were observed under microscope.The abilities of migration and invasion in vitro were observed by wound healing assay and Transwell assay.The changes of related molecules were determined by Western blot to explore the mechanism.RESULTS:The expression of CARMA3 at mRNA and protein levels in the HCT116 cells was the highest in the 4 colonic carcinoma cell lines.HCT116-shCARMA3 cells with stably-silenced CARMA3 gene were successfully established.Among them, HCT116-shCARMA3-93 cells showed the greatest inhibition of CARMA3 at mRNA and protein levels.Therefore,HCT116-shCARMA3-93 cells were chosen as the cell model.Compared with control group, the morphological changes of the HCT116-shCARMA3-93 cells had epithelial-mesenchymal transition (EMT) reversion.The abilities of proliferation, colony formation, migration and invasion in the HCT116-shCARMA3-93 cells were obviously suppressed (P<0.01).G0 /G1 phase proportion was increased and S phase proportion was correspondingly decreased (P<0.05).Bcl10 and NF-κB were down-regulated, and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT-1)showed no change.Cyclin D1 was decreased obviously and cyclin A declined slightly.Metastasis-related mar-kers matrix metalloproteinase (MMP)-2 and MMP-9 were reduced,MMP-7 remained unchanged, while tissue inhibitor of metalloproteinase(TIMP)-1 and TIMP-2 were up-regulated.Furthermore, EMT-associated molecule E-cadherin was increased, while N-cadherin, Snail, Slug and Twist were decreased to some extent.CONCLUSION:CARMA3 has an impact on the growth,migration and invasion of colonic carcinoma cell line, which is possibly related to NF-κB signaling pathway to change cell cycle and metastasis-related markers and to regulate EMT.

Evaluation of fMRI functional imaging in the curative effect of the acupuncture combined with traditional Chinese medicine in the treatment for patient with cerebral infarction / 中国医学装备

Objective: To explore the relationship between the combinative intervention therapy and clinical curative effect, through used function magnetic resonance imaging (fMRI) to observe the change of detection data for patients with cerebral infarction pre and post-intervention therapy of acupuncture combined with traditional Chinese medicine (TCM). Methods: 40 patients with cerebral infarction were divided into control group (20cases, received normal treatment)and observation group (20cases, received combinative treatment of acupuncture and TCM). Pre and post therapy, the patients of every group received evaluation about state of illness and detection of fMRI. The score of national institute of health stroke scale (NIHSS) was used to evaluate the degree of neurologic impairment, and analyze the imaging manifestations of fMRI on patients with cerebral infarction at basal ganglia who received acupuncture combined with TCM. Some cerebral functional imaging techniques, included blood oxygenation level dependent( BOLD), fMRI and diffusion tensor imaging (DTI), were used to grasp the changes of relevant functional region of brain and different brain regions connected with function region of patients with cerebral infarction before and after therapy. Results: The NIHSS score of observation group was significantly less than that of the control group (t=5.450, P<0.05), and the total efficiency of observation group (95%) was significantly higher than that of the control group (75%) (x2=4.329, P<0.05). And the differences of the activation frequency, activation volume, ADCavg values and the values of FA between the observation group and the control group were statistically significant (t=5.425, 2.760, 3.453, 5.513, P<0.05). Conclusion: Acupuncture combined with traditional Chinese medicine can efficiently improve the status of neurologic impairment for patients with cerebral infarction, and the clinical efficacy before and after treatment can preferably be observed by fMRI.

Cytotoxic effects against hepatoma cells by DCs loaded with exosome derived from Huh-7 cells / 中国免疫学杂志

Objective:To investigate the cytotoxic effects of CTL cell induced by DCs loaded with exosomes derived from hepatoma Huh-7 cells(T-exo).Methods: Exosomes derived from hepatoma Huh-7 cells were isolated and purified by combination of ultrafiltration centrifugation and sucrose density gradient centrifugation.Morphology of exosomes was observed under transmission electron microscopy and the expression of CD 9,CD63,HSP70 and AFP was detected by Western blot.DCs were induced with peripheral blood monocytes isolated from healthy donors.Flow cytometry was used to analysis surface markers of the DCs loaded with T-exo.WST-1 light absorption measurement was adopted to evaluate the T cell proliferation ability.Annexin-V/PI Flow cytometry were respectively used to examined cytotoxicity against the tumor cells.Results:Exosomes isolated and extracted from culture supernatant of Huh-7 cells presented as circular or elliptical vesicle with bilayer membrane , unequal in size , and with diameter of 50 to 100 nm.Western blot showed that the T-exo expressed CD9,CD63,HSP70 and AFP molecules.DCs loaded with T-exo caused significantly higher T cell pro-liferation and cytotoxic effect against AFP positive Huh-7 cells as compare to gainst AFP negative SMMC 7721 cells and un-loaded control group ( P<0.05 ).Conclusion: T-exosome loaded-DC can promote proliferation and induce significant cytotoxic effect of CTL against Huh-7 cells.

Effects of electroacupuncture on the activities of gliocytes of cervical spinal cord in rats with thyroid incisional pain / 中国针灸

<p><b>OBJECTIVE</b>To observe the impacts of electroacupuncture (EA) on microgliacytes and astrocytes of cervical spinal cord in rats with thyroid incisional pain and explore the mechanism of acupuncture anesthesia in thyroid surgery.</p><p><b>METHODS</b>Sixty Wistar male rats were randomized into a normal group, a model group, a Futu (LI 18) group, a Hegu (LI 4)-Neiguan (PC 6) group and a Zusanli (ST 36)-Yanglingquan (GB 34) group, 12 rats in each one. Except the normal group, a longitudinal incision, about 1.5 cm in length was done along the neck midline in the rats of the rest groups to prepare the model of thyroid incisional pain. In the Futu (LI 18) group, the Hegu (LI 4)-Neiguan (PC 6) group and the Zusanli (ST 36)-Yanglingquan (GB 34) group, after modeling for 4 h, 24 h and 48 h, EA was applied to bilateral "Futu" (LI 18), "Hegu" (LI 4) "Neiguan" (PC 6) and"Zusanli" (ST 36) "Yanglingquan" (GB 34) separately, once a day, continuously for 3 days. In the normal group and the model group, no any intervention was applied. The thermal radiant apparatus was used to detect the thermal pain threshold (PT). The fluorescence quantitative RT-PCR and the Western blotting (WB) were used to determine the expressions of protein and gene of microglia activation markers Iba1 and CD11b and the astrocyte specific protein marker, glial fibrillary acid protein (GFAP) in cervical spinal cord (Cto C) after intervention in the rats of each group.</p><p><b>RESULTS</b>After intervention, as compared with the normal group, in the model group, the neck PT was reduced apparently (<0.05), the expressions of Iba1 and CD11b and GFAP mRNA as well as the protein expressions in the spinal cord of Cto Cwere up-regulated apparently (<0.05,<0.01). As compared with the model group, in the Futu (LI 18) and the Hegu (LI 4)-Neiguan (PC 6) group, PT was increased significantly (both<0.05) and that did not change apparently in the Zusanli (ST 36)-Yanglingquan (GB 34) group (>0.05). In the Futu (LI 18) group, the protein and gene expressions of Iba1, CD11b and GFAP were lower than those in the model group (all<0.05). In the Hegu (LI 4)-Neiguan (PC 6) group, the expressions of Iba1 mRNA, CD11b protein, GFAP mRNA and protein were all lower apparently than those in the model group (all<0.05). In the Zusanli (ST 36)-Yanglingquan (GB 34) group, the expressions of Iba1, CD11b and GFAP proteins were not different significantly as compared with the model group (all>0.05). In the Zusanli (ST 36)-Yanglingquan (GB 34) group, the expressions of Iba1 mRNA and CD11b mRNA and protein expressions in the spinal cord of Cto Cwere higher apparently than those in the Futu (LI 18) group (<0.01,<0.05); the expressions of Iba1 mRNA and CD11b protein expressions were higher than those in the Hegu (LI 4)-Neiguan (PC 6) group (all<0.05); GFAP mRNA and protein expressions were higher apparently than those in the Futu (LI 18) group and the Hegu (LI 4)-Neiguan (PC 6) group (all<0.05).</p><p><b>CONCLUSIONS</b>EA at "Futu" (LI 18) or "Hegu" (LI 4), "Neiguan" (PC 6) relieves the acute neck incisional pain in the rats and its effect may be closely relevant with the down-regulation of the activities of microgliacytes and astrocytes in the spinal cords.</p>

Changes of Th17 and its related factors in hepatocellular carcinoma with hepatitis B virus infection / 中国免疫学杂志

Objective: To explore the significance of Th17 in hepatocellular carcinoma, expecially with HBV infection.Methods:Cytometric bead array(CBA) was employed to detect 5 cytokines(IL-2,IL-4,IL-6,IFN-γ,IL-17A)from 39 tumor and non-tumor tissues of HCC and combined clinical data for comparative statistic analysis.Results:The expression of IL-2,IL-4,IFN-γin liver cancer tissue[(4.61±0.28),(3.37±0.58),(3.08±1.08)pg/ml,respectively] was significant lower than non-cancer tissue [(5.57±0.59),(3.77±0.70),(3.69±1.20)pg/ml,respectively].Otherwise,the expression of IL-6,IL-17A in cancer tissue [(280.09±254.68), (2.66±1.66) pg/ml, respectively] was higher than non-cancer [(6.58 ±1.92), (1.49 ±0.98) pg/ml, respectively].And,whatever cancer or non-cancer tissue,the expression of IL-17A in tissue[(3.45±1.86)pg/ml] with high HBV load (>1 000 U/ml) was significant higher than tissue with low HBV load[(1.97±1.16)pg/ml].Conclusion: IL-17A was highly expressed in HCC,and IL-2,IL-4,IFN-γmay inhibit its expression,and IL-6 may promote it.Hepatitis B virus infection may promote Th17 expression,thereby reducing patient′s prognosis.

Efficacy of neuronavigation-guided selective percutaneous radiofrequency aiming at the target point semilunar ganglion in treatment of trigeminal neuralgia / 中华麻醉学杂志

Objective To evaluate the efficacy of neuronavigation-guided selective percutaneous radiofrequency aiming at the target point semilunar ganglion in the treatment of trigeminal neuralgia.Methods One hundred and forty-seven patients with primary trigeminal neuralgia of both sexes,aged 32-99 yr,with VAS score ≥ 8,were randomly divided into 2 groups:C-arm group (group C,n =72) and neuronavigation group (group N,n =72).Hartel anterior puncture was used and the C-arm guided puncture was performed at the target point foramen ovale in group C.In group N,three-dimensional reconstruction was made after the skull MRI images were transmired to the navigational system of StealthStation,and then the puncture path and point were designed after the target in the trigeminal ganglion was determined.The successful puncture and puncture-and radiofrequency-related complications were also recorded.The VAS scores were recorded at 1 and 7 days and 1,6,12 and 24 months after operation and the analgesic efficacy was evaluated.The therapeutic effect was evaluated by using Barrow Neurological Institute scoring system at 1 and 24 months after operation.Results No puncture-related side effects,damage to the oculomotor nerve or tinnitus developed in group N.The success rate of puncture at first attempt and the effective analgesia rate at different time points after operation were significantly higher,and the treatment effect was better in group N than in group C (P ＜ 0.05).There was no significant difference in the time for location of the nerve and incidence of facial numbness between the two groups (P ＞ 0.05).Conclusion Neuronavigation-guided selective percutaneous radiofrequency aiming at the target point semilunar ganglion in the treatment of trigeminal neuralgia provides a better efficacy,and a lower recurrence rate and a higher probability of successful puncture,with fewer complications.

Influence of Grb2-SH3 inhibitor peptidimer-c on the apoptosis-related genes expression in K562 cells / 肿瘤研究与临床

Objective To analyze the influence of peptidimer-c on the gene expression profiling of K562 cells and investigate the mechanism of peptidimer-c inducing the apoptosis and inhibiting proliferation of K562cells.Methods Trypan blue staining technique was performed for counting the number of living K562 cells treated with peptidimer-c.The ultrastructure changes of K562 cells treated with peptidimer-c was observed under transmission electron microscope.The Human U133 Plus 3.0 gene chips were used to detect the differentially expressed genes of K562 cells treated with peptidimer-c.Reverse transcription PCR was conducted to confirm some genes identified by gene chips.Results Peptidimer-c could induce the apoptosis and inhibit the proliferation of K562 cells.Peptidimer-c caused widely changes of the gene expression profiles of K562 cells.The chip data suggested that there were 529 differentially expressed genes,of which 455 genes were up-regulated and 74 genes were down-regulated.The relevant apoptotic genes were down-regulated markedly,including JUN,AXUD1,TNFRSF10B,etc.Fifteen of the differentially expressed genes were detected by RT-PCR,which was consistent with the chip data.Conclusion Peptidimer-c may induce aooptosis of K562 cells by activating the TNF/TNFR family and the JUN family.

Effect of trichostatin alone and combination with imatinb on the proliferation and apoptosis of the K562R cells / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of trichostatin A (TSA) alone and combination with imatinib on the proliferation and apoptosis of K562R cells.@*METHODS@#3-(4,5-dimethylthiazol-2-yl) -5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay was used to observe the proliferation of K562R cells and apoptosis was analyzed by annexin-V/propidium iodide(PI) staining.@*RESULTS@#After exposure to TSA, the proliferation of K562R cells was inhibited, and the effect was in both time- and dose-dependent manner. The apoptosis was induced. Combined with imatinib, the effect of proliferation inhibition was better.@*CONCLUSION@#TSA combined with imatinib can inhibit the proliferation of K562R cells and induce its apopotosis. TSA may become a new drug for imatinib-resistant patients.

Application of spiral computed tomography in clinical dental implantation / 中国基层医药

Objective To evaluate the value of spiral CT and panoramic radiographs in preoperative assessment the jaw condition of patients for dental implantation.Methods 80 patients required dental implant restoration,these patients were Manned by CT and panoramic radiographs in preoperative,then selected suitable patients for dental implant restoration,reconstructed the jaw based on spiral CT data and guided the dental implant design and implanration.Results The spiral CT examination could be more accurate selection criteria for the patients needed dental implant restoration and more accurately showed the situation of edentulous ridge bone.Conclusion The reconstructed of three-dimensional imaging of spiral CT could precisely show the bone situation in the jaw needed dental implant and the important anatomic structures,could effectively assist denture design and the direction and depth of dental implants.was more superiority than panoramic radiographs.

Study on MRI sequences in the diagnosis of articular cartilage injury of the knee joint / 中国基层医药

ObjectiveTo compare the accuracy of the four sequences of MRI in the diagnosis of articular cartilage injury of the knee and to investigate the advantage and shortage of the four sequences. In order to evaluate the most adequate sequence in detecting articular cartilage injury of the knee. Methods36 knee joints of 31 patients,underwent MRI scanning prior to arthroscopy included T1WI-TSE,T2 WI-TSE-SPIR, PDW-TSE-SPIR,3D-WATSC. Divided each knee side of every cartilage into five parts. Investigated and diagnosed the 180 articular cartilage surface according to Recha criteria by detecting and compared with arthroscopic examination respectively. The accurate criteria of the four sequences of MRI was sensitivity, specificity, accuracy. The criteria of correlation was the value of Kappa.ResultsCompared with the arthroscopic result which was the gold standard, the sensitivity, specificity, accuracy and Kappa value of the T1 W-TSE sequence was 63.8％ ,95.3％ ,78.8％ and 0. 403 respectively;The sensitivity,specificity ,accuracy and Kappa value of the T2WI-TSE-SPIR sequence was 56.3％ ,97.6％ ,76.1％ and 0. 353 respectively.The sensitivity,specificity,accuracy and Kappa value of the PDW-TSE-SPIR sequence was 79. 8％, 93.0％ ,86. 1％and 0. 642 respectively; The sensitivity, specificity, accuracy and Kappa value of the 3D-WATSC was 96. 8％,88. 3％ ,92.8％ and 0. 812 respectively. ConclusionThe accuracy and Kappa values of Fat-suppressed three-dimensiunal fast spoiled gradient-echo sequence (3D-WATSC)was superior to other sequences in the diagnosis of articular cartilage injury of the knee. The correlation between 3D-WATSC and arthroscopy in detecting cartilage injury was remarkable. 3D-WATSC had been deemed the most adequate sequence in detecting articular cartilage injury of the knee.

Comparison of the effects of two types of recruitment maneuver used in patients with ARDS / 中华急诊医学杂志

Objective To investigate and compare the effects of sustained inflation (SI) and pressure controlled ventilation (PCV) on lung recruitment in patients with ARDS, and on hemodynamics and respiratory mechanics of patients. Methods Ten patients with ARDS were included in this randomized clinical trial ( RCT), and SI (40 cmH20, 40s) and PCV (20 cmH20, 2 min) were successively applied to each patient under sedation, non-muscle relaxation state. There was a elution period between two types of recruitment maneuver (RM). Parameters of respiratory mechanics, gas exchange and hemodynamics were measured before RM (T0), 5 min after RM (T2) and one hour after RM (T3). Parameters of respiratory mechanics and hemodynamics were measured during the period of RM (Tl). Results (1) The PaO2 at T2 and T3 increased significantly in comparison with that at To ( P < 0.05), and there was no significant difference in PaO2 between two types of RM (P > 0.05). There were no significant differences in PaCO2 between two types of RM at each interval (P > 0.05). (2) The cardiac index ( CI) at T1 decreased significantly compared with that at To in two types of RM (P < 0.05), but there was difference in CI between two types of RM (P > 0.05). There were no differences in MAP and HR at these intervals (P > 0.05). (3) The functional residual capacity (FRC) at T2 and T3 increased significantly in comparison with that at To in two types of RM (P < 0.05). The static compliance (Cs) at T1 improved significantly (P < 0.05), but there was no difference in Cs between two types of RM ( P > 0.05). There was no difference in plateau pressure (Pplat) at all intervals (P >0.05). Conclusions The oxygenation, FRC, and Cs improve significantly in both SI-RM and PCV-RM, and the effects of two types of RM are similar. The SI-RM and PCV-RM have the similar impact on circulatory system during RM.

Curative effect of low dose cytarabine and aclarubin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on patients with the intermediate and high-risk myelodysplastic syndrome / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the curative effect and adverse effect of low dose cytarabine and aclarubin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on patients with the intermediate and high-risk myelodysplastic syndrome.@*METHODS@#A: total of 46 patients with intermediate and high-risk myelodysplastic syndrome was retrospectively analyzed. Twenty-eight patients received CAG regimen and 18 received conventional chemotherapy. CAG regimen: aclarubicin 10 mg/(m2.d)intravenously daily, Day 1~8; cytarabine 10 mg/ m2 subcutaneously once every 12 hours, Day 1~14; and subcutaneously use of granulocyte colony-stimulating factor 200 mug/(m2.d) until 12 hours before the last use of cytarabine. The initial outcome was evaluated after the first course of treatment. The responders received the second course. The ultimate therapeutic effect was evaluated after the 2 courses.@*RESULTS@#The overall response rate in the CAG regimen group was 78.6% (22/28). Thirteen patients (46.4%) responded, 5 (17.9%) showed partial response, and 4 (14.3%) hematologic improvement. The overall response rate in the conventional chemotherapy group was 50%(9/18). Six patients (33.3%) achieved complete response, 2 (11.1%) partial response, and 1(5.6%) hematologic improvement. The overall response rate of the CAG group was significantly higher than that in the control group (P<0.05). The adverse effects of CAG regimen were bearable.@*CONCLUSION@#With acceptable adverse effect, CAG regimen is effective for the intermediate and high-risk myelodysplastic syndrome. Long-time outcome needs further observation.

The research of the effect of oral external suction on environmental pollution control in dental clinic / 中国基层医药

Objective To examine the effect of oral external suction on environmental pollution of microorganism in dental clinic.Methods Aerobe was counted na observation index of air contamination and air sample of the area leveal 1m and 2.5 m,hight 1m,which using oral cavity collectors of aspirator or not was collected by the method of sedimentation.Results The datum of the group with oral cavity collectors of aspirator was much lower than the group without it.Conclusion Environmental pollution from tooth treatment in dental clinic can be reduced by using oral extemal suction.

Transfusion of partially HLA-matched irradiated allogeneic blood mononuclear cells for advanced renal-tell carcinoma / 中国癌症杂志

Background and purpose: Renal-cell carcinoma (RCC) is susceptible to immune therapy including the use of the nonmyeloablative allogeneic transplantation(NAT). However, NST can produce severe toxicity, so it might not be appropriate for many patients with metastatic RCC. Other novel allogeneic immunotherapies have been designed to induce an autologous immune response directed against the malignancy. This study evaluated the efficacy and safety of infusions of partially HLA-matched irradiated allogeneic blood mononuclear cells for advanced renal-cell carcinoma. Methods: Patients with histologically proven diagnosis of advanced RCC received infusions of partially HLA-matched allogeneic blood mononuclear cells. Repeat infusions were given every 8 weeks. Treatment was continued until disease progressed, unacceptable toxicity, or patient (or donor) choice. Results: Eight patients were enrolled. After every infusion, 6 patients received an oral administration of thalidomide daily with 100-300 mg/d for 2 months. One patient had durable complete response. Five stable diseases and two progress diseases were observed. In eight patients, time to progression and survival were 320 and 879+days, respectively. Severe toxicity was not observed. Conclusion: Infusions of partially HLA-matcbed irradiated allogeneic blood mononuclear cells for advanced RCC may induce some antitumor effects and deserves further study.

The influence of Chlamydia trachmatis and Ureaplasma urealyticum infection on perinatal out-come and nursing / 中国实用护理杂志

Objective To study the influence of Chiamydia trachmatis (CT) and Ureaplasma ure-alyticum (UU) infection on pregnant outcome and neonates. Methods 562 pregnant women were ran-domly selected, their cervical secretion was collected and detected for CT and UU by culture method. Groups were divided according to the results. All of them were followed-up till delivery. Results The in-cidence of infection of group CT、group UU、group CT and UU were 22.1%、28.8% and 3.7%;Compared with negative group,the group with positive result of CT、UU、 CT and UU had significant higher incidence of preterm labor, premature rupture of membranes, low weight infant and neonates pneumonia. Conclusions The infection of CT、UU can result in adverse pregnant outcome, preterm labor, premature rupture of mem-branes, low weight infant and neonate pneumonia.