Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective To investigate the effect of melanoma associated antigen D1 (Mage-D1)on mouse femoral bone mass and mineralization ability of mouse bone marrow mesenchymal cells (BMSCs)and its potential molecular mechanism.Methods Female Mage-D1 gene knockout heterozygous mice and male wild-type (WT)mice were subjected as parent mice to breed Mage-D1 gene knockout homozygous (Mage-D1 KO)mice.PCR and agarose gel electrophoresis were used to identify male Mage-D1 knockout (Mage-D1 KO)mice and littermate male wild-type (WT)mice.Micro-CT scanning was performed to observe mouse femoral bone mass,and ELISA and chemical assay were employed to detect serum levels of calcium,phosphorus,calcitonin,and parathyroid hormone in mice.After primary cultured BMSCs were identified with flow cytometry,immunofluorescence staining was utilized to detect the expression of Mage-D1 in BMSCs.BMSCs were infected by Mage-D1 silencing lentivirus,and then the cells were divided into negative control group (sh-NC)and silencing group (sh-Mage-D1).Cell scratch assay was conducted to detect the migration ability of BMSCs,and flow cytometry and CCK-8 assay were conducted to detect the cycle change and proliferation ability of BMSCs.After mineralization induction,alkaline phosphatase (ALP) staining and alizarin red staining were performed;RT-qPCR and Western blotting were used to measure the expression levels of ALP,Runx2 and Col1.RT-qPCR was used to detect mineralization-related genes p75NTR and Msx1.Results Compared with the WT mice,the femoral cortical bone thickness,cortical bone mineral content,cancellous bone mineral content,trabecular number,and cancellous bone surface density were decreased,and trabecular separation was increased in the Mage-D1 knockout homozygous mice (P<0.05).There were no significant changes in the serum levels of calcium,phosphorus,calcitonin and parathyroid hormone in mice after Mage-D1 knockout.Mage-D1 was expressed in the whole BMSCs and was highly expressed in the nucleus and perinuclear regions.Compared with the sh-NC BMSCs,the sh-Mage-D1 group had decreased proliferation ability (P<0.01),enhanced migration ability (P<0.01),and decreased expression of ALP,Runx2 and Col1 genes (P<0.05)and protein (P<0.01)after mineralization induction,milder ALP and alizarin red stain,and lower expression levels of p75NTR and Msx1.Conclusion Mage-D1 knockout can significantly reduce femur bone mass in mice.It can promote the proliferation and inhibit migration of BMSCs,and positively regulate their mineralization in vitro,and the p75NTR-Dlx1/Msx1 signaling axis may be involved in the regulation of bone metabolism by Mage-D1.

Objective:To search, evaluate and summarize the best evidence of intervention and management of eating behavior in children with autism, so as to provide evidence for medical staff and caregivers of children with autism to manage eating behavior problems.Methods:According to the evidence pyramid "6S" model, the clinical decisions, recommended practices, guidelines, evidence summaries, expert consensus, systematic reviews and randomized controlled trials on the intervention and management of eating behavior in children with ASD were systematically searched from domestic and foreign databases, related guide websites and professional association websites. The search period was from the establishment of the database to March 31th, 2023. The quality of the guide was independently evaluated by 4 researchers, and the remaining articles were evaluated by 2 researchers. Content extraction, evidence integration and grading of the included articles were carried out, and the level of evidence recommendation was formed through the expert meeting.Results:A total of 19 articles were included, including 3 guidelines, 1 expert consensus, 13 systematic reviews and 2 randomized controlled trials. This paper summarized 25 best evidence from 5 aspects, including the common eating behavior problems of children with autism, the assessment of eating behavior problems, causes, consequences and intervention methods.Conclusions:The best evidence summarized in this study provides a basis for the management of eating behavior problems in children with autism. It is suggested that clinical staff should fully consider the clinical context when applying the evidence, and formulate more detailed and feasible eating behavior intervention programs combined with the children and their families.

Clinical novitiate is not only a significant part in the training of basic comprehensive ability of clinical medicine students,but also a weak link in current teaching practice link. This research is guided by the educational reform of the"5+3"talent training mode and it carries out reforms by constructing three-stage novitiate mode, realizing curriculum integration and PBL teaching as well as multi-dimensional performance appraisal etc.It is student-centered and lays emphasis on developing students' autonomous learning ability,basic clinical skills and thinking ability,so as to improve the training quality of the medical professionals and provide a referable novitiate teaching mode for the training of medicine professionals under the new situation.

Objective To construct the recombinant eukaryotic expression plasmids of human adenylyl cyclase-associated protein 1 (CAP1)and to explore its intracellular location and functions.Methods By using Hela cDNA as the template,the cDNAs encoding CAP1 was amplified by PCR and inserted into pCMV-Myc vector to construct the recombinant plasmid.The recombinant plasmid was transfected into 293 cells using lipofectamine 2000.The protein expression and the intracellular location of the inserted gene were confirmed by Western blotting and immunofluorescence,respectively.Scratch-repair experiment was used to detect the cancer cells’ migration ability.Results The recombinant eukaryotic expression plasmid of human CAP1 was successfully constructed and transfected into eukaryote cells.The recombinant plasmid was successfully expressed in eukaryote cells.CAP1 was located in the cytoplasm.The results of scratch-repair experiment showed that the overexpression of CAP1 could significantly inhibit the cells’ migration.Conclusion CAP1 recombinant plasmid was successfully expressed in eukaryotic cells.CAP1 protein was located in the cytoplasm.The overexpression of CAP1 inhibited cell migration. The present study provides important experimental evidence for further study on CAP1.

Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.

Objective To evaluate the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in ovarian cancer cell lines, and to investigate the biological effects of down-regulated MALAT-1 on OVCAR3 cells.Methods qRT-PCR analysis was used to examine the expression level of MALAT-1 gene in ovarian cancer cells, including ES-2, A2780, SKOV3 and OVCAR3 cell lines.For functional research, four shRNA oligos specially targeting MALAT-1 and a empty vector were designed and constructed into pGPU6/GFP/Neo, then transfected into OVCAR3 cells.qRT-PCR was used to confirm the effective suppression of MALAT-1.Changes of proliferation and adhesion of cells were analyzed by CCK-8 and adhesion assays.Wound-healing, transwell migration and invasion assays were used to examine migration and invasion of MALAT-l-silencing cells in vitro.Results The expression of MALAT-1 gene in OVCAR3 cells was high, and qRT-PCR results confirmed successfully the knockdown of MALAT-1 after transient transfection.After successful suppression of MALAT-1, the proliferation, wound-healing and adhesion ability in vitro were inhibited to some degree.In transwell migration assay, the number of migration cells in MALAT-1-silencing group was 52.17±4.48, which is much less than that in the negative and control groups (286.50± 12.23 and 295.67±6.96, respectively).In invasion assay, the number of invasion cells passing the transwell membrane in MALAT-1-silencing group (37.33±2.40) was also decreased significantly, compared to that in the negative and control groups (239.00±15.72 and 222.67±20.85, P ＜ 0.05).Conclusions shRNA-mediated silence of MALAT-1 can effectively inhibit the proliferation, adhesion, migration and invasion abilities of ovarian cancer cell line OVCAR3 in vitro, indicating MALAT-1 is expected to be a target gene for the treatment of ovarian cancer.

Objective To investigate the effect of citric acid and ambroxol on clearing insoluble particles of depleted uranium in rat lungs by establishing a tracheal perfusion model.Methods One hundred and fifty male Wistar rats were randomly divided into model exposure group, normal control group(NC group), depleted uranium exposure group(DU), citric acid treatment group( CA) , ambroxol treatment group( AM) and citric acid+ambroxol treatment group( CA+AM) . The rats were sacrificed on 7, 15 and 30 days.Uranium content in the lungs was detected by microwave digestion method, pathological changes in the lungs were observed, and inflammatory factors of lung homogenates were detected.Results Compared to DU control group, the intrapulmonary uranium deposit amount in experimental groups was significantly reduced on 7 and 15 days (P<0.05).HE stained lung tissue showed that the pathological changes in treatment groups were less significant than in DU control group.The level of IL-1α,IL-1β,and IL-2 was significantly lower than in DU control, but the level of MCP-1 and MIP-1 was observably higher.Conclusion Citric acid and ambroxol can evidently improve the clear-ance of lung uranium and reduce damnification of lung tissues.Drug treatment can reduce the level of pulmonary inflamma-tory cytokines alleviate the chronic inflammation in the lungs, and enhance the capacity of macrophage to recruitment.

Objective To observe the effect of S-band micro-wave long-term intermittent irradiation on endocrine function in rats.Methods A total of 192 rats (male and female) were randomly divided into the sham-irradiation (normal control) groups and the irradiation groups.The irradiation groups were exposed with micro-wave at 3 dosages of 4,10 and 20 mW/cm2 for 6 min twice a week for 12 weeks,while no administration was given to control group.The endocrine parameters in blood serum were examined by radioimmunoassay at 4,8,12 week during irradiation and 4 week post-irradiation.Results After the irradiation of S-band microwave,parts of the endocrine parameters changed.T3 in famale rats decreased at first and then increased,especially in 10 mW/cm2 group at 8 and 12 week,20 mW/cm2 group at 4 and 12week(t =-2.586,-2.642,-5.075,-4.365,P <0.05).FT3 in famale rats had the similar trend asT3,significantly lower in 4 and 10 mW/cm2 groups than that in the control group at 4 week (t = 2.275,2.510,P <0.05),then increased,especially in three irradiation groups at 12 week (t =-2.636,-2.851,-5.240,P < 0.05).TSH decreased at 4 week,especially in 10 mW/cm2 group (t = 2.300,P < 0.05) ; and then increased in the irradiation groups at 20 mW/cm2 at 8 and 12 week (t =-2.838,-3.651,P <0.05).COR and ACTH in male rats showed changes in volatility,in which the 4,10 and 20 mW/cm2 groups at 8 week increased significantly (t =-2.772,-2.234,-2.505,P < 0.05),while 20 mW/cm2 group at 12 week decreased significantly (t=3.067,P < 0.05).E2 in female rats was slightly lower in irradiation groups at 4 week than the control group,then increased,especially in 10 mW/cm2 group at 8 week,three irradiation groups at 12 week (t =-2.322,-3.179,-2.655,-4.716,P < 0.05),and returned to the normal at 4 week post-irradiation,significantly lower in 4 mW/cm2 group than that in the control group (t = 2.250,P < 0.05).T in male rats increased first and then decreased,especially in 10 mW/cm2 group at 8 week(t =-2.435,P < 0.05).After exposure the above indexes restored to some extent.Conclusions The long-term intermittent irradiation of S-band microwave can cause adverse effects on the endocrine function of rats.

OBJECTIVE: To understand the usage of MP3 and effects on hearing of middle school students in Xi'an, and discuss controlling strategies. METHOD: Stratified random cluster sampling method was used in the 1567 middle school students in Xi'an through questionnaire survey, ear examination and hearing examination, data were analysed by the SPSS13.0 statistical software. RESULT: 1) The rate of holding MP3 in the middle school students was 85.2%. Average daily use time was (1.41 +/- 1.11) h. 2) The noise group of pure tone hearing threshold was significantly higher compared with the control group (P<0.01), and increased the detection rate of hearing loss with the increasing use of MP3. 3) The detection rate of symptoms increased with the increasing use of MP3. CONCLUSION The usage of MP3 can harm hearing in middle school students, which can result in neurasthenic syndrome.
Adolescent ; Audiometry, Pure-Tone ; Auditory Threshold ; Data Collection ; Female ; Hearing Loss ; etiology ; Hearing Tests ; Humans ; MP3-Player ; Male ; Students ; Surveys and Questionnaires