Objective:To summarize and evaluate the relevant evidence of exercise intervention for adult hemophiliacs patients at home and abroad, and to provide a reference basis for healthcare professionals to individualize exercise programs for adult hemophiliacs.Methods:A computer-based "6s" evidence resource pyramid model was used to systematically search for guidelines, evidence summaries, expert consensuses, systematic reviews and random controlled trials on exercise of adult hemophiliacsin databases such as China Biology Medicine disc, Wanfang Med Online, UpToDate, BMJ Best Practice, PubMed, etc, from the time of creation to January 31, 2023. Quality assessment, evidence extraction and evidence integration of relevant literature was performed by two researchers, with a third researcher adjudicating in case of conflicting opinions. An expert panel meeting was conducted to rate the level of evidence extracted.Results:A total of 15 literatures were included. Among them, 4 guidelines, 2 expert consensuses, 2 systematic reviews, and 7 randomized controlled trials. A total of 28 pieces of best evidence were developed, encompassing 6 aspects of exercise assessment, exercise modality, exercise duration, exercise intensity, precautions, and benefits of exercise.Conclusions:Before exercising, hemophiliacs should be assessed by a multidisciplinary team and an appropriate exercise program should be developed to maintain normal body functions and improve the quality of life of hemophiliacs.

Objective To investigate the factors influencing the prognosis of complex intracranial aneurysms treated with pipeline flow-directed device(PED)and to develop a nomogram prediction model.Methods The clinical data of a total of 98 patients with complex intracranial aneurysm,who were admitted to the Anyue County People's Hospital or the Second Affiliated Hospital of Guilin Medical College of China from January 2021 to April 2023 to receive PED treatment,were retrospectively analyzed.The influencing factors that might affect the prognosis of patients with complex intracranial aneurysm were collected.According to the modified Rankin Scale(mRS)score,the patients were divided into good prognosis group(being defined as mRS ≤2 points)and poor prognosis group(being defined as mRS＞2 points).The clinical data were compared between the two groups,and a nomogram model was established and validated.Results In the 98 patients,poor prognosis was seen in 10(10.20％).The differences in age,history of hypertension,history of diabetes mellitus,clopidogrel resistance,Fisher classification,repeated aneurysm rupture,aneurysm location,aneurysm size,aneurysm neck,multiple lesions,and Hunt-Hess grade on admission between good prognosis group and poor prognosis group were statistically significant(all P＜0.05).Multivariate analysis revealed that history of hypertension,clopidogrel resistance,repeated aneurysm rupture,aneurysm location,multiple lesions,and Hunt-Hess grade were the independent factors influencing the prognosis of patients with complex intracranial aneurysm after receiving PED treatment.The AUC of the nomogram model in predicting the prognosis of PED for complex intracranial aneurysms was 0.849(95％CI=0.758-0.939).The predicted curves of the model group and validation group were basically fitted to the standard curves.The results of the decision curve analysis showed that the net benefit to patients was greater than 0 when the probability threshold of the nomogram model for predicting a poor prognosis of PED for complex intracranial aneurysms was 0.10-0.90.Conclusion The factors causing poor prognosis of PED for complex intracranial aneurysms mainly include history of hypertension,clopidogrel resistance,repeated aneurysm rupture,etc.The nomogram model established in this study can predict the risk of poor prognosis in patients with complicated intracranial aneurysm after receiving PED treatment.

Objective To analyze the genetic etiology of a fetus with growth restriction,short long bones,small head circumference and enhanced kidney echoes,and explore the clinical significance of nonsense mutations in the NIPBL gene.Methods The clinical data of the fetus and his/her parents were collected.The variation sites of the NIPBL gene were verified by the chromosome karyotype a-nalysis of amniotic fluid,copy number variation detection in the human genome(CNV-seq),whole exome sequencing(WES)and Sanger sequencing.The databases such as China National Knowledge Infrastructure(CNKI),Wanfang Data,Wanfang Medical,and Pubmed were searched to further analyze the relationship between clinical symptoms and gene mutation sites in the fetus.Results The sequencing results showed that there was c.4555A>T heterozygous mutation in exon 21 of the NIPBL gene in the fetus,and that the same mutation was not detected in his/her parents.The above variation had not been included in databases such as Human Exon Data-base(ExAC),1000 genomes(1000G)and Genome Aggregation Database(gnomAD),and were comprehensively judged as harmful variation.Conclusion The detection of the nonsense variation,c.4555A>T(p.Lys1519?),in the NIPBL gene may provide experi-mental evidence for the prenatal diagnosis and fertility in this family.

Inflammation underlies a wide variety of physiological and pathological processes, and plays a pivotal role in controlling pathogen infection. C1q/tumor necrosis factor (TNF) related proteins (CTRPs), a newly discovered adipokine family with conservative structure and wide distribution, has attracted increasing attention. The CTRP family consists of more than 15 members which fall into the characteristic C1q domain. Increasing studies have demonstrated that CTRPs are involved in the onset and development of inflammation and metabolism as well as related diseases, including myocardial infarction, sepsis and tumors. Here, we first clarified the characteristic domains of CTRPs, and then elucidated their roles in inflammatory-related diseases. Taken together, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.
Humans ; Complement C1q/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Inflammation/metabolism* ; Myocardial Infarction

Objective:To evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt.Methods:Data of 24 patients with gastric fundal varices with large spontaneous shunt (the smallest diameter was 5-15 mm) treated by EUS-guided coil embolization combined with endoscopic cyanoacrylate injection in Renmin Hospital of Wuhan University from December 2016 to December 2020 were retrospectively analyzed. The short-term efficacy (the rates of technical success, five-day rebleeding and six-week mortality) and long-term efficacy (the rates of one-year rebleeding, one-year mortality and three-year mortality) and safety (ectopic embolism) were evaluated.Results:The technical success rate was 91.7% (22/24), and the five-day rebleeding rate was 0 (0/22). Computed tomography angiography of portal vein reexamined 2 days after the treatment showed embolism of splenic vein in 1 patient (4.5%). The median follow-up time was 14.9 months (ranging 1.0-48.6 months) and 2 patients were lost during follow-up. The six-week mortality was 0 (0/20), and the one-year rebleeding rate was 35.0% (7/20). Among 12 patients who underwent endoscopy in the follow-up, 5 had aggravation of esophageal varices, and 5 had aggravation of portal hypertension gastropathy. The one-year and three-year mortalities were 5.0% (1/20) and 20.0% (4/20), respectively, neither of which was related to such events as bleeding or ectopic embolism.Conclusion:EUS-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt is effective and safe in short term, with a low rate of ectopic embolism. Long-term efficacy and safety need to be further confirmed.

OBJECTIVE：To provide reference for the c onstruction of subject diagnosis and treatment scheme in drug clinical trials. METHODS ：The subject diagnosis and treatment module was developed and implemented in our hospital on the basis of CTMS，and its effects were evaluated. RESULTS ：A subject diagnosis and treatment module was established in CTMS of our hospital. Within one year from the launch of the module in the middle of October ，2019，the overall number of subjects in the group showed an increasing trend ，and the overall mean dropout rate of subjects was 0.16％. The data interface of CTMS system ， hospital information system （HIS），laboratory information management system ，medical imaging information system had been established，so as to realize the synchronization of subject information （displaying subject identification in HIS system ）and the interaction of diagnosis and treatment information and billing data （patients and subjects were charged separately ）. Since the launch of the module ，the amount of data generated by the interface had been increasing ，and the number of departments producing the subject diagnosis and treatment business had been increasing month by month. Compared with subject diagnosis and treatment project based on HIS system ，the number of subject diagnosis and treatment business based on CTMS system was increased significantly（P＜0.05）. CONCLUSIONS ：The subject diagnosis and treatment module based on CTMS improves the efficiency of subject diagnosis and treatment project implementation and financial settlement ，and realizes the efficient implementation of drug clinical trial projects in large general hospitals.

Objective The aim of this study was to investigate the dosimetric advantages of Gating in the treatment of prima-ry hepatic cancer with large segmentation. Methods A retrospective analysis of 10 patients with primary liver cancer from August 2017 to November 2018 after interventional therapy was performed using three consecutive phases of end-tidal phase to achieve pa-tient-controlled large-segment radiotherapy. Ten patients underwent 4DCT localization scan,and 10 respiratory phase sequences were reconstructed by respiratory wave-form,and the images were transmitted to the MIM6. 7. 6 workstation. In the MIM workstation, full-time phase maximum density projection(MIP-10),full-time phase average density projection(Mean-10),end-expiration 3 phase maximum density projection(MIP-3) and end-expiration 3 phase average density projection( Mean-3) were generated re-spectively,where MIP was used for target delineation and Mean for dose calculation. The radiotherapy doctor delineated IGTV-10 and IGTV-3 on the MIM workstation,and released CTV-10,CTV-3,PTV-10 and PTV-3 to compare the volume differences of the target area. After the target area was drawn,the image was transmitted from the MIM workstation to the Eclipse treatment planning sys-tem,and the full-time phase plan(Plan-10)with the same conditions and three consecutive phase-phase gating plans(Plan-3) were prepared. The prescriptive dosage was given at 50 Gy/10 f/2weeks. Comparing the HI and CI of the target area,the comparison of organs at risk included: the average dose of liver Dmean,the irradiation volume of liver less than 15Gy,the Dmax of small intestine, the Dmax of colon, the Dmax of stomach, the average dose of the kidney Dmean, the heart Dmax, and the spinal cord Dmax. Results The volume of the target area delineated at the end of expiratory phase was less than that of the target area outlined by the full-time phase in IGTV,CTV and PTV,and the difference was statistically significant(P<0. 05). In the two groups of seven field coplanar lage-segment radiotherapy plans,the 3-phase respiratory gating plan significantly reduced the dose of the organs at risk, and the difference was statistically significant(P<0. 05). At the same time,there was no statistically difference in the HI and CI be-tween of the two groups(P>0. 05). Conclusion The gated target area delineation and planning design of the three consecutive pha-ses of end-tidal phase reduce the volume of IGTV,CTV and PTV target regions compared with the selection of full-time phase,and have obvious advantages in the planned dosimetry. The irradiation dose that threatens the organs is worthy of being promoted and ap-plied in the large-scale radiotherapy of liver cancer.

Objective To explore the effect of tea polyphenols on the growth of human papillomavirus 16 (HPV16) subgenes-immortalized human cervical epithelial cells (H8 cells).Methods Cultured H8 cells were divided into 5 groups to be treated with 0 (control group),6.25,12.5,25 and 50 mg/L tea polyphenols respectively for 24,36,and 48 hours,and then cell counting kit-8 (CCK8)assay was performed to detect cell proliferation.After 24 hours of incubation,flow cytometry was conducted to detect cell apoptosis and cell cycle,and fluorescence microscopy to observe the morphology of apoptotic cells.Results After incubation with tea polyphenols at different concentrations for 24,36 and 48 hours,the proliferation of H8 cells was inhibited,and 12.5 mg/L tea polyphenols could inhibit the relative growth rate of H8 cells in a time-dependent manner.Flow cytometry showed that there was a significant difference in cell apoptosis rate among the 6.25-,12.5-,25-,50-mg/L tea polyphenols groups and the control group (52.62％ ± 0.62％,52.22％ ± 0.72％,42.52％ ± 0.90％,45.96％ ± 2.11％,29.96％ ± 0.70％ respectively,F =272.0,P ＜ 0.05).Moreover,all the tea polyphenol groups showed significantly increased cell apoptosis rate compared with the control group (all P ＜ 0.05).Fluorescence microscopy showed karyopyknosis,nuclear fragmentation and other typical apoptotic morphological changes in H8 cells in tea polyphenols groups.There were significant differences in the percentage of cells in G1,G2 phase and cell proliferation index among the 5 groups (all P ＜ 0.05).Compared with the control group,the 6.25-,12.5-,25-mg/L tea polyphenols groups showed significantly increased percentage of cells in G1 phase (55.96％ ± 0.72％,54.12％ ± 3.20％,65.30％ ± 1.51％ respectively,all P ＜ 0.05),but significantly decreased percentage of cells in G2 phase (3.17 ± 1.82％,4.94 ± 1.46％,4.65 ± 4.26％ respectively,all P ＜ 0.05) and lower cell proliferation index(0.44 ± 0.01,0.46 ± 0.02,0.36 ± 0.01 respectively,all P ＜ 0.05).Conclusion Tea polyphenols can inhibit the proliferation of H8 cells,induce cell apoptosis,and block cell cycle progression.

Cryptosporidium spp.are protozoan parasites that infect the epithelial cells of the gstrointestinal tract of hosts.In humans,cryptosporidiosis is usually a self-limiting infection in immunocompetent individuals,but severe diarrhea and dissemination to extra-intestinal sites can occur in high-risk individuals,such as the very young,the elderly,immunedeficiency individuals,particularly in HIV-positive patients.So far,molecular epidemiological data have confirmed the presence of 30 species and over 40 genotypes with genus Cryptosporidium,with 21 species and genotypes being found in humans.The majority of human cryptosporidiosis cases are responsible for C.hominis and C.parvum.Human cases caused by C.meleagridis,C.ubiquitum,C.felis and C.canis have been increasing.Besides that,with data accumulation of molecular epidemiology of human cryptosporidiosis,some more Cryptosporidium species and genotypes were newly identified in humans.This paper mainly reviews epidemiology status of these new emerging Cryptosporidium species and genotypes in humans.

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.
Animals ; Bacillus ; Bacteria ; Chemokine CCL2 ; Flow Cytometry ; Injections, Intraperitoneal ; Interferon-gamma ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Lymph Nodes ; Mice* ; Mycobacterium bovis ; Mycobacterium* ; Pathology ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha