OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

Objective To evaluate the application of three deep learning algorithms in automatic segmentation of clinical target volumes (CTVs) in high-dose-rate brachytherapy after surgery for endometrial carcinoma. Methods A dataset comprising computed tomography scans from 306 post-surgery patients with endometrial carcinoma was divided into three subsets: 246 cases for training, 30 cases for validation, and 30 cases for testing. Three deep convolutional neural network models, 3D U-Net, 3D Res U-Net, and V-Net, were compared for CTV segmentation. Several commonly used quantitative metrics were employed, i.e., Dice similarity coefficient, Hausdorff distance, 95th percentile of Hausdorff distance, and Intersection over Union. Results During the testing phase, CTV segmentation with 3D U-Net, 3D Res U-Net, and V-Net showed a mean Dice similarity coefficient of 0.90 ± 0.07, 0.95 ± 0.06, and 0.95 ± 0.06, a mean Hausdorff distance of 2.51 ± 1.70, 0.96 ± 1.01, and 0.98 ± 0.95 mm, a mean 95th percentile of Hausdorff distance of 1.33 ± 1.02, 0.65 ± 0.91, and 0.40 ± 0.72 mm, and a mean Intersection over Union of 0.85 ± 0.11, 0.91 ± 0.09, and 0.92 ± 0.09, respectively. Segmentation based on V-Net was similarly to that performed by experienced radiation oncologists. The CTV segmentation time was < 3.2 s, which could save the work time of clinicians. Conclusion V-Net is better than other models in CTV segmentation as indicated by quantitative metrics and clinician assessment. Additionally, the method is highly consistent with the ground truth, reducing inter-doctor variability and treatment time.

As the country with the largest number of new cancer cases and deaths,China faces a serious situation with a large cancer population base,low relative survival rate,and low adherence to cancer screening.Neighboring Japan,which has the longest life expectancy in the world,has a much higher relative survival rate than China,despite having a similarly high cancer rate,due to its well-established system of cancer prevention and control.Being an Asian country,the major prevalent cancers in China and Japan are similar in spectrum and can be referred to more.This article introduces the construction of Japan's cancer life-cycle prevention and control system of"cancer prevention","cancer care",and"coexistence with cancer"starting from the three major goals of Japan's cancer prevention and control program,and focuses on the improvement of cancer screening in Japan and the improvement of cancer survival in China.It also highlights the means and methods used to increase the cancer screening rate in Japan,with a view to providing suggestions for cancer prevention and control in China.

Background::China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019.Methods::The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported.Results::The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends.Conclusions::The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model.The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA.Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/ NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.

Objective To explore the mechanisms of Buyang Huanwu Decoction(BYHWD)in reducing oxidative stress levels to protect the blood-brain barrier(BBB)in cerebral ischemia/reperfusion injury(CIRI)rats.Methods A middle cerebral artery occlusion/reperfusion(MCAO/R)model in rats was established via wire embolization method.PeriCam PSI laser speckle flow imaging was applied to detect whether the model was successfully established.Neurological deficits in the rats were evaluated by Zea Longa score,and histopathological changes in the rat brain were observed by HE staining.The degree of brain edema was detected by the dry and wet weight method.BBB permeability was detected by Evans blue staining,and ultrastructural changes to the BBB were observed by transmission electron microscopy.The levels of ROS,MDA and SOD activities,which are related to oxidative stress,were detected using kits.The expression levels of matrix metalloproteinase-9(MMP-9)were detected by immunohistochemical staining and Western blot.The expression levels of Occludin,ZO-1,and Claudin-5 tight junction proteins were determined via immunofluorescence and Western blot.Results BYHWD reduced neurological deficit scores,alleviated brain histopathological damage,alleviated BBB structural disruption,prolonged the appearance of dense regions in the tight junction structure,attenuated edema of the brain on the ischemic side,and reduced BBB permeability in MCAO/R rats.BYHWD decreased the levels of ROS and MDA,increased the activity of SOD,decreased the expression levels of MMP-9,and increased the expression levels of Occludin,Claudin-5 and ZO-1.Conclusions BYHWD can increase BBB tight junction protein expression levels,reduce the permeability of the BBB,protect the ultrastructure of the BBB,and reduce brain edema,and its mechanisms may be related to its antioxidant activity and inhibition of MMP-9 activation.

Objective:To evaluate the efficacy of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT) in the treatment of adult patients with port-wine stains (PWS) in China, and to analyze factors influencing the efficacy.Methods:A retrospective study was conducted on the data from 265 adult patients with PWS who underwent HMME-PDT at the Department of Dermatology, West China Hospital, Sichuan University from February 2017 to October 2023. Patients were intravenously injected with hemoporfin at doses of 5 - 6.5 mg/kg, followed by irradiation with a 532-nm green light-emitting diode at the energy density of 100 - 130 J/cm 2 (power density, 85 - 100 mW/cm 2) for 19 - 25 minutes. Treatments were conducted every 2 - 6 months. The treatment response in the treated area was observed after each treatment, and the clinical efficacy was assessed at least two months after the last treatment. Chi-square test was used to analyze the differences in efficacy between groups. Results:Among the 265 adult patients with PWS, the male to female ratio was 90∶175, the patients' age ranged from 18 to 56 years (26.48 ± 6.88 years), and they underwent 1 to 8 treatment sessions (2.67 ± 1.33 sessions). After treatment, 102 (38.4%) patients achieved complete remission, 74 (27.9%) achieved marked improvement, 59 (22.2%) had moderate improvement, and 30 (11.3%) showed no response, resulting in an overall response rate of 88.7%. Among 146 patients without hypertrophic lesions, 69 (47.3%) achieved complete remission, with a response rate of 92.5%; among 102 with slightly thickened lesions, 32 (31.4%) achieved complete remission, with a response rate of 87.3%; among 17 with markedly thickened lesions, only 1 achieved complete remission, and 11 achieved marked improvement. Among 50 patients who received more than 3 treatment sessions, 28 (56%) had complete remission, with a response rate of 100%; among 45 who received only one session of treatment, 5 (11.1%) achieved complete remission, with a response rate of 68.9%. Among 232 patients without soft tissue hyperplasia, 95 (40.9%) achieved complete remission, with a response rate of 88.8%; among 33 with soft tissue hyperplasia, 7 (21.2%) achieved complete remission, with a response rate of 87.9%. The therapeutic effects significantly differed among patients with different lesion thicknesses, among those with different treatment sessions, as well as between patients with soft tissue hyperplasia and those without (all P < 0.05). There were no significant differences in the therapeutic effect among patients of different genders, different ages, with different lesion colors, as well as between patients with nodules and those without, and between patients with treatment history and those without (all P > 0.05). During and after the treatment, patients experienced varying degrees of swelling, burning sensation, pain, and itching, all of which could be relieved by common treatment; scars occurred in 10 (3.8%) patients, and were managed by symptomatic treatment; no systemic adverse reactions, such as drug allergies or impairment of liver and kidney function, were observed during the treatment. Conclusions:HMME-PDT is safe and effective in the treatment of adult patient with PWS. The therapeutic effect of HMME-PDT was associated with lesion thickening and soft tissue hyperplasia, and increased with the increase in treatment sessions.

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model.The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA.Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/ NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model.The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA.Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/ NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.