Objective To study the inhibitory effects of adenovirus-mediated fusion gene system driven by KDR promoter(AdKDR-CDglyTK) on angiogenesis and growth of pancreatic cancer.Methods The nude mice model was reproduced bearing pancreatic cancer cell lines Capan-2.Twenty nude mice were randomly and equally divided into four groups: AdKDR-CDglyTK and 5-FC/GCV were injected to the animals of group Ⅰ;group Ⅱ received 5-FC/GCV injection,group Ⅲ received AdKDR-CDglyTK injection,and group Ⅳ as control,received neither AdKDR-CDglyTK nor 5-FC/GCV.AdKDR-CDglyTK was injected directly into the tumor,while 5-FC/GCV was given by intraperitoneal injection.The treatment efficiency in each group was observed and the tumor microvessel density(MVD) was analyzed.RT-PCR was employed to examine the expression of CDglyTK in tumors.Results Tumor growth was dramatically inhibited in group Ⅰ,while no significant difference was found in group Ⅱ,group Ⅲ and group Ⅳ.The MVD in the four groups were 2.08?0.79,10.01?0.77,9.91?0.63 and 10.39?1.35,respectively(F=93.29,P=0.00).The MVD decreased significantly in group Ⅰ compared to the other three groups(P0.05).RT-PCR showed that a 2.4kB fragment had been amplified in the tumor tissues of groupⅠand group Ⅲ,but not in groupⅡand group Ⅳ.Conclusion AdKDR-CDglyTK with 5-FC and GCV can significantly inhibit the angiogenesis and growth of implanted pancreatic cancer in nude mice.

Objective To investigate the curative effect of the adenovirus-mediated fusion gene system driven by KDR promoter (AdKDR-CDglyTK) on a model of pancreatic cancer. Methods By using transplantation of the cultivated cells, human pancreatic cell line Capan-2 was injected subcutaneously on the back of nude mice to establish the animal model of the pancreatic cancer. Twenty nude mice were divided randomly and equally into four groups. The mice in group Ⅰ were injected with AdKDR-CDglyTK and 5-FC/GCV, those in group Ⅱ were injected with 5-FC/GCV, those in group Ⅲwere injected with AdKDR-CDglyTK and those in group Ⅳ received no any injection. AdKDR-CDglyTK was injected directly into the tumor and 5-FC/GCV was given by intraperitoneal injection. The observing parameters included common status, tumor bulk, tumor weight, inhibition rate of tumor growth, pathology, immunohistochemistry and treatment effect in each group. Electron microscopy was performed to observe the pathological changes of cells. The apoptotic cells in tumor were detected using the TUNEL assay. The expression of CDglyTK in tumors from each group was examined by RT-PCR. Results Tumor growth was dramatically inhibited in group Ⅰ. Tumor growth has no significant difference among groupⅡ , group Ⅲ and group Ⅳ. The apoptotic rate (34.20±4.60)% was significantly increased in group Ⅰ (F= 243. 22, P= 0. 00) and it had no significant difference among groupⅡ , group Ⅲ and group Ⅳ (P＞0.05). Conclusion AdKDR-CDglyTK with 5-FC/GCV can obviously inhibit the growth of human KDR-expressing pancreatic cell line Capan-2 and induce the cell apoptosis in vivo. The probable molecular mechanism lies in the facts that the system can cause a decline in the level of Bcl-2.

Objective To investigate the curative effect of an adenovirus-mediated fusion gene system driven by VEGF promoter (AdVEGF-CDglyTK) on a nude mouse model of colorectal cancer and analyze the mechanism underlying its therapeutic effect.Methods The animal model of the colorectal cancer was established by using transplantation of the cultivated cells,human colorectal cell line LoVo,via subcutaneous injection on the back of nude mice.Twenty nude mice were equally divided into four groups:group Ⅰ received injection of AdVEGF-CDgiyTK plus 5-flurocytosine/ganciclovir(5-FC/GCV);group Ⅱwere given 5-FC/GCV;group Ⅲ were with AdVEGF-CDglyTK;group Ⅳ were used as control.Results CDglyTK was expressed exclusively in the tumor tissues from the group Ⅰ and Ⅲ by RT-PCR.The phenotype and pathological analysis showed that tumor growth was dramatically inhibited in group Ⅰwhen compared with other three groups,while no significant difference was found between group Ⅱ,group Ⅲ and group Ⅳ.The TUNEL assay demonstrated that the apoptosis rate of 38.65% ± 4.20 significantly increased in group Ⅰ when compared with other three groups (F = 397.530,P =0.000).The tumor microvessel density of 3.08±0.79 decreased significantly in group Ⅰ (F = 34.081,P = 0.000) when compared with other three groups.Conclusion The results suggested that AdVEGF-CDglyTK with 5-FC/GCV can inhibit the tumor growth of colorectal cancer significantly in vivo by a mechanism of systeminduced apoptosis and the efficient suppression of angiogenesis.

ABSTRACT:Objective To study the platelet changes in patients with unstable angina with different blood glucose ,and their related biochemical index changes ,and their relationship with global registry of acute coronary events (GRACE) score .Methods For this clinical study ,we enrolled 82 patients diagnosed with unstable angina , 47 of whom were male and 35 were female .Upon admission ,their random blood glucose was tested .According to different blood glucose values ,they were divided into normal blood glucose group (<6 .1 mmol/L) and high blood glucose (≥ 6 .1 mmol/L ) group . The following clinical data were compared between the two groups :age , hypertension ,diabetes ,smoking history ,and BMI .We detected EF (% ) ,HBA1C ,glucose ,LDL‐C ,HDL‐C ,TG , LPA ,CREA ,UA ,hsCRP ,BNP ,CKMB ,CTNI ,D‐Dimer ,and GRACE risk scores .We compared the platelet test results :PLT ,P‐LCR ,PDW ,and MPV .We also detected the relationship of MPV with hsCRP ,D‐Dimers and GRACE risk scores .Results MPV ,hsCRP ,and GRACE risk score differed significantly between normal blood glucose group and high blood glucose group (P<0 .05) .In the latter group ,MPV had significant correlation with hsCRP ,D‐Dimers and GRACE risk score ( r=0 .28 , r=0 .41 , r=0 .56 , P<0 .05) .Conclusion Hyperglycemia in patients with unstable angina causes the increase of MPV , change of the inflammatory marker hsCRP , and increase of clinical GRACE risk score .Abnormal MPV may predict the increased risk of unstable angina in patients with hyperglycemia upon hospitalization .

Objective To investigate the differential expression of P57kip2 and CDK5 in neural tube defects t(NTD) from the normal ,and provide the clue for the research of the molecular mechanism of the normal neurula formation .Methods A cDNA mi-croarray containing 1 100 known genes was used to compare differences in P57kip2 and CDK5 gene expression between the normal control group and the retinoic acid(RA)-induced NTD group on embryonic(E) day 9 .5 and 10 .5 .Two differentially expressed genes were randomly selected from the two groups for Northern blotting to verify the results of the cDNA microarray .Results Compared the differences of between P57kip2 and CDK5 in normal and E9 .5 d ,E10 .5 d ,E9 .5 d-NTD ,E10 .5 d-NTD ,P57kip2 and CDK5 expression was significantly up-regulated in the before and after the formation of the normal neurulation ,but them showed a downward trend in retinoic acid (RA)-induced NTD(including two phase E9 .5 d and E10 .5 d) .Conclusion P57kip2 and CDK5 in-volved in the physiological process of NTD ,and provide the useful clue for the research of the molecular mechanism of the normal neurula formation .

Objective:To assess the practical value of visual scores of magnetic resonance imaging(MRI)features in the diagnosis and classification of dementia with Lewy bodies(DLB).Methods:In this study, 102 DLB patients were prospectively recruited, with 102 cognitively normal elderly people as the normal control group(NC).All included subjects underwent MRI examinations and neuropsychological assessments.Based on the clinical dementia rating(CDR)scale, DLB patients were divided into a mild(CDR=1.0), a moderate(CDR=2.0)and a severe(CDR=3.0)group.The results of MRI were scored visually and the rating scales included medial temporal lobe atrophy(MTA), global cortical atrophy-frontal subscale(GCA-F), posterior cortical atrophy(PCA), white matter lesions(the Fazekas scale), cerebral microbleeds(CMBs), and the Evans Index(EI).Statistical differences were compared between the DLB and NC groups and between DLB patients with different degrees of cognitive impairment.Results:In terms of neuropsychology, the Mini-Mental State Examination(MMSE) score of the DLB group[16.0(11.0, 21.0)]was statistically significantly lower than that of the NC group[29.0(28.0, 30.0)]( Z=-12.31, P<0.001), the Montreal Cognitive Assessment(MoCA)score of the DLB group[9.5(6.0, 15.0)]was statistically significantly lower than that of the NC group[28.0(27.0, 29.0)]( Z=-12.40, P<0.001), and the Activities of Daily Living(ADL)score of the DLB group[32.0(23.8, 40.0)]was statistically significantly higher than that of the NC group[20.0(20.0, 20.0)]( Z=-11.98, P<0.001).The scores of all MRI visual assessment scales in DLB patients were statistically significantly higher than those in the NC group( P<0.001).There were significant differences in MTA scores between DLB patients with different degrees of cognitive impairment( P0<0.001).The MTA score of the mild group[1.0(1.0, 1.0)]was statistically significantly lower than that of the moderate group[2.0(1.0, 2.0)]( P1<0.001, P2<0.001); The MTA score of the moderate group[2.0(1.0, 2.0)]was statistically significantly lower than that of the severe group[2.0(2.0, 3.0)]( P1=0.003, P2=0.010). Conclusions:This study has for the first time after comprehensively evaluated the value of various visual scores in DLB diagnosis, MTA can be used to help diagnose DLB and distinguish the severity of DLB, providing a new supplemental tool for clinical diagnosis.

Objective:To investigate the clinical effect of modified atlantooccipital decompression combined with occipitocervical internal fixation on Chiari type I malformation combined with syringomyelia and atlantoaxial dislocation.Methods:Twenty-five patients with Chiari I malformation combined with syringomyelia and atlantoaxial dislocation accepted by modified atlantooccipital decompression combined with occipitocervical internal fixation in our hospital from January 2011 to March 2019. The clinical data of these patients were retrospectively analyzed. The changes of peak velocity of cerebrospinal fluid in the dorsal part of the spinal cord, electrophysiological results, atlantodental interval (ADI) values, sizes of syringomyelia, and Chicago Chiari outcome scale (CCOS) scores before and after operation were compared.Results:The peak velocity of cerebrospinal fluid in the dorsal spinal cord after surgery ([3.25±0.47] cm/s) was statistically higher in these patients than that before surgery ([2.13±0.19] cm/s, P<0.05). As compared with the preoperative results, ADI values, sizes of syringomyelia, and proportion of patients with abnormal electrophysiological monitoring at 6 months after surgery were significantly decreased, and CCOS scores at 6 months after surgery were significantly increased ( P<0.05). There were no new nerve function damage, infection, cerebrospinal fluid leakage, paralysis, respiratory failure or death. Conclusions:Modified atlantooccipital decompression combined with occipitocervical internal fixation plays effective role in atlantooccipital decompression and atlantoaxial anatomical reduction in patients with Chiari malformation type I combined with syringomyelia and atlantoaxial dislocation. The remission rate of syringomyelia is high, the symptoms and signs improve obviously, and the postoperative complications are less.

Objective:To investigate the application value of multimodal image three-dimensional reconstruction combined with facial nerve tracking in acoustic neuroma surgery.Methods:Forty-five patients with single acoustic neuroma accepted primary surgical treatment at Department of Neurosurgery, Yibin Hospital, West China Hospital, Sichuan University from November 2018 to June 2022 were chosen. The head, skull, brain tissues, arteriovenous system, tumor and facial nerves were reconstructed preoperatively by multimodal three-dimensional image reconstruction combined with facial nerve tracking. Preoperative planning was carried out according to the relationship between tumor and surrounding structures. The accuracy of facial nerve tracking was evaluated by intraoperative microscopic observation and nerve electrophysiological monitoring. House-Brackmann (H-B) criteria was used to evaluate facial nerve functions 2 weeks after surgery. Three months after surgery, all patients underwent enhanced MRI scanning, and combined with intraoperative findings, the degrees of acoustic neuroma resection were determined.Results:The facial nerves and their relations with acoustic neuroma were successfully tracked in all 45 patients; as confirmed by intraoperative microscopy and nerve electrophysiological monitoring, the results of facial nerves and their relations with acoustic neuroma were consistent in 42 patients and inconsistent in 3 patients. Using intraoperative nerve electrophysiological monitoring as gold standard, the accuracy of multimodal image three-dimensional reconstruction of the facial nerves was 93.3%. Preoperative facial nerve tracking results were highly consistent with intraoperative nerve electrophysiological monitoring results (Kappa=0.903, P<0.001). The facial nerves were intraoperatively preserved in 91.1% patients (41/45), and the facial nerve function was good in 86.7% patients (39/45) at 2 weeks after surgery. The total/subtotal resection rate of acoustic neuroma was 88.9% (40/45). No death, cerebrospinal fluid leakage, hematoma, or cerebral infarction were noted during the perioperative period. Conclusion:Multimodal image three-dimensional reconstruction combined with facial nerve tracking can help to protect blood vessels and nerves, improve total resection rate and facial nerve function retention rate in surgery of acoustic neuroma.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

OBJECTIVE: Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. METHODS: PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. RESULTS: Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. CONCLUSION Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.