Objective To investigate any neuroprotective effect of hyperbaric oxygenation (HBO) on the mitochondria of dopaminergic neurons using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease.Methods Forty-eight male SPF C57BL/6 mice were randomly assigned to either a normal control group (treated with a 30 ml/kg intraperitoneal injection of physiological saline once a day),a model group ( treated with a 30 mg/kg intraperitoneal injection of MPTP once a day) or an HBO therapy group ( treated with a 30 mg/kg intraperitoneal injection of MPTP and HBO once a day).The expression of tyrosine hydroxylase (TH) protein,PINK1 protein and caspase-3 in brain tissue was measured using immunohistochemistry and Western blotting assays.Results Compared with the control group,the expression levels of TH protein and PINK1 protein were significantly lower in the neurons of the substantia nigra in the model mice.HBO therapy upregulated the expression of TH and PINK1 protein.Compared with the control group,the average level of caspase-3 protein in the neurons of the substantia nigra in the model mice was significantly higher.HBO therapy downregulates the expression of caspase-3 protein.Conclusions HBO can protect mitochondria and inhibit apoptosis of dopaminergic neurons in the substantia nigra of brains with (MPTP-induced) Parkinson's disease by upregulating the expression of PINK1 protein and TH protein,and downregulating the expression of caspase-3 protein.

Objective:To report a Chinese family with a novel ABCD1 gene mutation at c.332T>G (p.V111G) site and discuss its clinical characteristics and molecular mechanism.Methods:The clinical data, laboratory examination, and imaging examination results were analyzed to make the clinical diagnosis of a middle-aged onset patient from the First Affiliated Hospital of Zhengzhou University in May 2017. High-throughput sequencing was used to discover a novel ABCD1 gene mutation. Sanger sequencing was used to find out whether other family members contain the same ABCD1 gene mutation. The pathogenicity of this mutation was explored by protein structure prediction and pathogenicity analysis. Adrenoleukodystrophy protein-green fluorescent protein (ALDP-GFP) and ALDP-GFP (V111G) plasmids were constructed and human embryonic kidney 293 cells were transfected, then immunofluorescence and Western blotting were used to explore the molecular mechanism of this mutation (completed in Henan Provincial People′s Hospital).Results:The proband (a 39-year-old male) was diagnosed as adrenomyeloneuropathy, a subset of X-linked adrenoleukodystrophy, with a novel heterozygous missense mutation in the ABCD1 gene at c.332T>G (p.V111G) site, and his mother and two daughters were all carriers. Protein structure prediction and pathogenicity results suggested that this mutation is pathogenic. Overexpression of ALDP-GFP (V111G) in the human embryonic kidney 293 cells resulted in a significant decrease in the expression levels of ALDP and the abnormal localization from the peroxisomal membrane to the cytoplasm, accompanied by significant down-regulation of LC3-Ⅱ/LC3-Ⅰ and beclin-1.Conclusion:c.332T>G (p.V111G) is a novel pathogenic mutation in the ABCD1 gene, which causes adrenomyeloneuropathy by impairing autophagy.

Objective To detect the methylation status of p16 gene promoter in CD4~+ T cells of patients with systemic lupus erythematosus(SEE),and its significance in the pathogenesis of SLE.Methods The pl 6 gene promoter methylation in peripheral CD4~+ T cells was detected with the Taqman probe-based realtime PCR(Methylight)technology in 28 patients with SLE and 20 healthy human controls.Results The methylation rate of p16 gene promoter in peripheral CD4~+ T cells was higher in patients with SLE than that in the controls(35.7%VS 10%,x~2=4.11,P<0.05).There was no correlation between SLE disease activity index (SLEDAI)and the normalized index of methylation(NIM)of p16 gene promoter(r_s=-0.29,P>0.05).Conclusion The methylation status of p16 gene promoter is aberrant in CD4~+ T,:ells of SLE patients,suggesting that the hypermethylation of p16 gene plays a certain role in the pathogenesis of SLE.

BACKGROUND: At present, there is few reports about using middl ecerebral artery obstraction (MCAO) model to determine the repair course of cerebral infarction during functional training.OBJECTIVE: To determine the effect of electro-stimulating therapy on promoting the rehabilitation of cerebral infarction and its mechanism.DESIGN: Randomized controlled study.SETTING: Animal Center and Electron Microscope Laboratory of Zhongshan University.MATERIALS: The experiment was carried out in the Animal Center of Zhongshan Medical College and Neurological Laboratory of the First Affiliated Hospital of Zhongshang University from January 2002 to December2004. A total of 200 healthy males SD rats, aged 3 months and weighing 90-110 g, were selected. According to the following criteria: SBP＞180mmHg (1 mmHg=0.133 kPa), BWT score of MCAO models which were reproduced by RHRSP was 1, totally 180 RHRSP were admitted to the research and divided into electro-stimulating therapy group (n=90) and control group (n=90).METHODS: Electro-stimulating was given to four accupuncture points of the paralyzed limbs of rats. The electro-stimulating treatment was given about 30 minutes once a day. And a therapy course was 6 days, and between two therapy courses there was one-day break. At the end of 1st, 3rd,6th and 9th therapy courses, the brain of motor function and tissue in marginal zone of cerebral infarction were assayed as follow: [1] The beam walking test (BWT, 1 as severe disorder and 7 as normal). [2] Electron microscope. [3] Astrpcyte glial fibriliary acidic protein, neurofilament protein and microtubule-associated protein-2 were assayed with immunohistochemistry. Five fields of each slice in the two groups were randomly selected to add up the positive cell number. Totally 30 positive cells of glial fibriliary acidic protein was selected to assay average absorbency (A) of positive cellular plasm. [4] Apoptosis of neurons were observed with in situ end-labeling (ISEL). [5] Brain-micro vasodilatatio was observed according to the criteria of one complete microvessel account under the field.MAIN OUTCOME MEASURES: [1] Scores of motor function; [2] Ultramicrostructure of cranial neurons and astrocyte; [3] Cranial glial fibriliary acidic protein, neurofilament protein and microtubule-associated protein-2;[4] Apoptosis of neurons; [5] Diastole of cerebral microvessel.RESULTS: Totally 180 rats were eligible while 20 rats were excluded because of their BWT score＞1 after MCAO operation. [1] Results of beam walking test (BWT): Functional recovery of paralysis limbs in electric stimulation group was better than that in control group from the third to the ninth course. In the ninth course, 6 points of rats in electric stimulation group was more than that in control group (42, 46, χ2=15.4, P ＜ 0.01). [2]Positive absorbency of cerebral glial fibriliary acidic protein: That in electric stimulation group was higher than that in control group in the 3rd, 6th,and 9th [(52.97±0.59)% vs (46.40±0.56)%; (49.44±0.80)% vs (46.40±0.56)%;(43.25±0.48)% vs (34.20±0.50)%, P ＜ 0.05]. [3] Assay of neurofilament protein: That in electric stimulation group was higher than that in control group in the 6th and 9th course [(22.9±2.7)% vs (11.9±2.3)%; (26.5±1.7)%vs (11.7±1.5)%, P ＜ 0.05]. [4] Assay of microtubule-associated protein-2:That in electric stimulation group was higher than that in control group in the 6th and 9th course [(21.7±1.3)% vs (11.3±1.1)%; (24.4±2.1)% vs(11.9±2.3)%, P ＜ 0.05]. [5] Apoptosis of neurons: There was not significantly different between the two groups. [6] Results of open number of cerebral microvessel: That in electric stimulation group was higher than that in control group in the 1st, 3rd, 6th and 9th course (33 vs 19; 48 vs 31;45 vs 25; 46 vs 23, Z=-2.309, P ＜ 0.05).CONCLUSION: Electro-stimulating treatment can promote motor function of paralyzed limbs, which was due to that electro-stimulating treatment may promote extinction of the swollen feet of astrocytes, reinforce neurons activity and arouse the dilatation of cerebral capillary which promote the microvascular dilatation in order to improve cerebral blood circulation.

Objective To investigate the efficacy of permanent left ventricular epicardial pacing through left lateral thoracotomy in children with complete atrioventricular block (CAVB)or complete left bundle branch block (CLBBB)as well as its effects on heart synchronization.Methods Permanent left ventricular epicardial pacemakers were implanted through left lateral thoracotomy in 26 children with CAVB or CLBBB in Heart Center,the First Affiliated Hospital of Tsinghua University.These children aged (2.3 ±2.1 )years old (1 month -9 years old),weight (1 1 .2 ± 5.8)kg (5 -32 kg),among them 1 5 cases were male and 1 1 cases were female.Among the 26 patients,24 patients had CAVB and 2 patients had dilated cardiomyopathy secondary to CLBBB.Fifteen children who visited the Pediatrics Department for acute upper respiratory tract infection were chosen as control group.The efficacy of left ventricular epi-cardial pacemakers was analyzed and its effects on heart synchronization were observed by using tissue Doppler imaging (TDI).Results Implantations of pacemakers were successfully conducted in all the 26 patients with no complications associated with operations.Left atrial and ventricular dual chamber epicardial pacemakers were implanted in 21 patients and left ventricular single chamber epicardial pacemakers were implanted in 5 patients.Within the follow -up period of (28.2 ±1 5.1 )months (1 month -51 months),atrial and ventricular leads were 1 00% effective.No significant diffe-rence was found in atrial electrode sensing,ventricular electrode threshold and ventricular electrode impedance com-pared with those during implantation(P >0.05).For the 6 patients with preoperative cardiac insufficiency,their left ventricular diastolic diameters decreased from (48.50 ±1 1 .1 0)mm to (40.67 ±6.40)mm after operation,and the difference was significant (t =2.96,P =0.030);but left ventricular ejection fraction increased from 0.27 ±0.08 to 0.53 ±0.08 after operation,and the difference was significant (t =-5.02,P =0.004).Two patients with right ven-tricular pacing developed pacemaker syndrome and were switched to left ventricular epicardial pacing.Their cardiac function returned to normal 1 .5 and 2.0 years later,respectively.Fifteen patients received evaluation of heart synchroni-zation by TDI.No significant difference was found in LVEF,septal -to -lateral wall motion delay,septal -to -posterior wall motion delay and standard deviation of Standard deviation of the peak tissue velocity between these 2 groups(all P >0.05).Conclusions For children requiring epicardial pacing,left ventricular epicardial pacing is safe and effec-tive,which can protect left ventricular systolic synchronization,prevent or reverse the pacemaker syndrome.

Moral distress generally exists in the nursing interns and has a far-reaching impact. This paper analyzed and summarized the current situation, influencing factors and coping strategies of the nursing interns at home and abroad, in order to provide reference for promoting the professional development of nursing students, strengthening their professional beliefs and stabilizing the nursing team.

Objective K93T point mutation exists in the quinoid dihydropteridine reductase ( QDPR) of OLEFT rats which catalyzes QDPR into tetrahydrobinopterin(BH4), while dihydrofolate reductase(DHFR) can reduce QDPR to BH4, which implies crosstalk between hydrobiopterin and folate metabolism.By investigating the influence of QDPR expression on DHFR expression of NRK-52E cells, the article aimed to find out the possible underlying mechanism of QDPR gene in diabetic nephropathy ( DN). Methods Western blot was performed to identify the expression level in NRK-52E cell under high glucose ambience and DHFR pro-tein expression of OLETF rats.NRK-52E cells were transfected by the lentivirus to establish no-load overexpression, overexpressed QDPR and knockdown QDPR models.Each group was given 5.4 mmol/L normal sugar medium and 30mmol/L in high glucose ambi-ence for 72 hours'cell cultivation to simulate DN model.Observation was made on the influence of QDPR gene expression levels on DHFR in high glucose ambience. Results The western blot analysis revealed that DHFR protein decreased in NHG group( [0.33 ± 0.16] vs [0.64 ±0.5], P<0.05) and OLETF rats cortex ([0.56 ±0.16] vs [1.03 ±0.12], P<0.01).In high glucose ambi-ence, compared with LV-OCON-HG group, the protein expression of DHFR was significantly decreased in LV-QDPR-HG group ([0.12 ±0.09] vs [0.63 ±0.08], P<0.01).No difference was found in the comparison of DHFR expression levels between LV-SHQDPR-HG and LV-SHCON-HG group. Conclusion DHFR protein expression decreases in NRK-52E cells of high glucose and LOLETF rat model, which suggests that DHFR protein plays an important role in the development of DN.QDPR overexpression leads to the decreased expression of DHFR, which implies that overexpressed QDPR influences the occurrence and process of DN by down-regulating DHFR expression level.

Objective:To compare the effect of uPWS R15 software based on deep learning with MIM-Maestro 6.9 software based on atlas library to automatically delineate the organs at risk of prostate cancer in order to provide a reference for clinical application.Methods:The CT data of 90 prostate cancer patients admitted to the Department of Oncology Radiotherapy of the Affiliated Hospital of North Sichuan Medical College from 2018 to 2022 were retrospectively selected. Based on the uPWS R15 software developed by Shanghai United Imaging Medical Technology Company and the MIM-Maestro 6.9 software developed by Beijing Mingwei Vision Medical Software Company, the effects of uPWS and MIM software on automatic delineation of organs at risk were evaluated according to five parameters, including delineation time (T), Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), Hausdorff distance (HD) and the mean distance to agreement (MDA).Results:The sketching time of uPWS software was less than that of MIM software. There were no significant differences in the sketching effect of femoral head and skin between the two software (all P>0.05). The delineation of right kidney ( tMDA=-3.43, zDSC=-4.03, zJSC=-4.16, P<0.05), left kidney ( tMDA=-3.87, zDSC=-4.18, zJSC=-4.41, P<0.05), small intestine ( tMDA=-8.57, zDSC=-9.99, tJSC=14.21, P<0.05) and rectum ( zMDA=-4.00, tDSC=-9.98, tJSC= 9.72, P< 0.05) except HD, was statistically different. The bladder ( z=-7.88, -9.00, -8.17, -8.74, P<0.05) and spinalcord ( z=-3.87, -4.43, 4.03, 3.05, P<0.05) were also delineated with significant differences. The DSC automatically delineated by uPWS software was >0.7, while the DSC automatically delineated by MIM software was >0.7 for all other organs at risk except small intestine and rectum. In addition, the HD, MDA and JSC values of the organs at risk (bilateral femoral head, bilateral kidneys, spinal cord, bladder, skin, rectum and small intestine) automatically delineated by uPWS software were generally better than those with MIM software. Conclusions:The uPWS software outlines better than the MIM software, but the MIM software can also be used clinically with modifications to the small bowel and rectum, saving a great deal of time in preparation for radiation therapy.

Objective:To systematically review the experience of nurses′ in providing home-based hospice care, so as to provide a basis for improving the quality of home-based hospice care and the nursing service system.Methods:Qualitative researches on nurses′ experience of providing home-based hospice care were retrieved from the Cochrane Library, PubMed,Web of Science, EBSCO, Medline, China National Knowledge Internet, China Biomedical Literature Database, Wanfang Database, VIP Database from inception to April 1, 2022. Adopting Joanna Briggs Institute Critical Appraisal Tool (2016) to evaluate the quality of included studies, the Meta-synthesis was used to explain and integrate the research results.Results:A total of 9 articles were included. This study extracted 23 clear results, 8 new categories, and 3 integrated results, including the significance of nurses′ acceptance of home-based hospice care; positive and negative emotions coexist when nurses provide home-based hospice care; challenges in implementing home-based hospice care.Conclusions:The development of home-based hospice care service is helpful to provide continuous care for the terminally ill patients and improve their quality of life, but at the same time, the ability of home-based hospice care of nurses should be further improved and the related policy guarantee should be perfected to promote the steady development of home-based hospice care in China.

BACKGROUNDBecause invasion and metastasis of cancer threaten seriously human's life, it is of more important clinical significance to understand and evaluate the biologic behavior of can-(cer) correctly. Abnormal expression of E-cadherin and β-catenin plays important roles in invasion and metastasis of cancer. The objective of this study is to investigate their expression in non-small cell lung cancer (NSCLC) and to find out their correlation with histological type, cell differentiation, metastasis and prognosis of NSCLC.

METHODSThe expression of E-cadherin and β-catenin was detected in 129 NSCLC tissues by high sensitive S-P immunohistochemical method.

RESULTSThe abnormal expression rate of E-cadherin and β-catenin was 62.0% and 65.1% respectively. The abnormal expression rate of E-cadherin in squamous cell carcinoma was much higher than that in adenocarcinoma (P < 0.05). The abnormal expression rate of E-cadherin and β-catenin in poorly differentiated cells was significantly higher than that in well and moderately differentiated cells (P < 0.05, P < 0.05). Stage III/IV NSCLC showed markedly higher abnormal expression rate of E-cadherin and β-catenin than stage I/II NSCLC did (P < 0.01, P < 0.01). The abnormal expression rate of E-cadherin and β-catenin in patients with lymphatic metastasis was significantly higher than that in those without lymphatic metastasis (P < 0.05, P < 0.01). The mean survival duration and 5-year survival rate in patients with normal E-cadherin and β-catenin expression were remarkably higher than those in patients with abnormal expression (P < 0.05, P < 0.01).

CONCLUSIONSThe abnormal expression of E-cadherin and β-catenin is closely related to histological type, differentiation and metastasis in NSCLC. Detection of their expression might be helpful to predict prognosis of NSCLC.