[Clinical characteristics of severe pre-eclampsia in a single tertiary referral center of Xiamen City].

Objective: To explore the key points for preventing and reducing severe pre-eclampsia (SPE) and its severe complications in the tertiary medical referral system of a second-tier city by analyzing the clinical characteristics of SPE. Methods: The clinical data of 341 patients with SPE who terminated pregnancy in Women and Children's Hospital, School of Medicine, Xiamen University, from January 1, 2020 to December 31, 2022 were retrospectively analyzed, and the pre-eclampsia (PE) risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the maternal and perinatal outcomes. Results: Among the 341 cases of SPE, 92 cases were in the referral group and 249 cases were in the central group. (1) Analysis of PE risk factors: there was no statistical difference in the proportion of risk factors of PE between these two groups [75.0% (69/92) vs 71.9% (179/249); χ2=0.328, P=0.567]. (2) Analysis of clinical features: the gestational ages at the PE early warning factors onset, at the PE first symptom onset and at SPE diagnosed, pregnancy terminated and onset of SPE severe complications in the referral group were significantly earlier than those in the central group (all P<0.05), the proportions of terminating pregnancy before 32 weeks of gestation, between 32 and 34 weeks of gestation, intensive care unit (ICU), neonatal ICU hospitalization and fetal growth restriction in single pregnancies were higher than those in the central group, while the live birth rate was lower than that in the central group (all P<0.05). (3) Analysis of SPE severe complications: the rates of SPE severe complications in the referral group was higher than that in the central group [28.3% (26/92) vs 13.7% (34/249); χ2=9.885, P=0.002]. Among them, the rates of placental abruption [7.6% (7/92) vs 2.8% (7/249); χ2=3.927, P=0.048] and still birth [6.5% (6/92) vs 0.4% (1/249); χ2=9.656, P=0.002] in the referral group were significantly higher than those in the central group. (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (9.8%, 9/92), referral after SPE diagnosed (63.0%, 58/92), referral after detection of SPE early warning signs (20.7%, 19/92) and referral after detection of PE risk factors (6.5%, 6/92). The gestational ages at SPE diagnosed and pregnancy terminated in group of referral after onset of SPE severe complications and group of referral after SPE diagnosed were significantly earlier than those in group of referral after detection of PE early warning signs and group of referral after detection of PE risk factors (P<0.05). The earlier the referral, the higher the live birth rates (P<0.05). Conclusions: The tertiary referral center of the second-tier city plays an important role in reducing the maternal and perinatal damage of PE. The timing of referral in primary medical institutions is the key point of reducing the occurrence of SPE severe complications and maternal, perinatal damage of PE. It is necessary for medical institutions of all levels in all regions to improve the ability of early identification and early intervention for PE, to enhance the awareness of SPE and its severe complications prevention and control. Primary medical institutions should especially pay attention to raise the consciousness of PE risk factors and early warning signs, and to improve the ability of PE risk factors and early warning signs screening.

[Study on protective effects and mechanisms of total glucosides of Paeony on Graves disease in BALB/c mice].

Objective: To investigate the protective effect and its immunoregulatory mechanism of Total Glucosides of Paeony (TGP) against Graves' Disease (GD) model on BALB/c mice. Methods: Fifty female (6 weeks old, weighing 16-18 g) BALB/c mice of specific pathogen free were divided into control group according to random number table method, model group, early low-dose TGP intervention group (250 mg·kg-1·d-1), early high-dose TGP intervention group (500 mg·kg-1·d-1), and late TGP intervention group, with 10 mice in each group. Except the control group, the other 4 groups were immunized 3 times (0, 3rd, and 6th week) with recombinant adenovirus expressing the thyroid stimulating hormone receptor (TSHR) A subunit to establish the GD model. The early low-dose and high-dose intervention group were given diets containing different doses of TGP throughout the whole process, and the late intervention group was given diets containing low doses of TGP from the 1st week after the 2nd immunization (week 4). The levels of thyrotropin receptor antibody (TRAb) and total thyroxine (TT4) were detected in the tail venous blood of mice at the 4th week. At the 10th week, the serum TRAb and TT4 levels and the ratio of regulatory T cells (Treg) in each group were detected, and the pathological changes of thyroid tissue were observed. Serum helper T cell 1(Th1) and Th2 cell-related factors interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factors-α (TNF-α) were detected to investigate the protective effect of TGP on GD model in BALB/c mice and its mechanism. Results: At the 4th week, The level of TT4 [(55.07±12.89) µg/L] in early high-dose intervention group was lower than that in model group [(74.33±8.63) µg/L] (all P<0.05). The level of TT4 in early low-dose intervention group and late intervention group and model group had no statistical significance (all P>0.05). TRAb level of mice between early low-dose, early high-dose, late intervention groups and model group was no significant difference (all P>0.05). At the 10th week, TRAb [(90.00±26.89) U/L] and TT4[(32.66±8.11) µg/L] levels in the early high-dose intervention group were lower than those in the model group [(396.97±95.35) U/L, (73.70±16.33) µg/L] (all P<0.05). The TRAb and TT4 levels in the early low-dose intervention group and late intervention group were not significantly different from those in the model group (all P>0.05). The thyroid tissue of hyperthyroidism mice in the early high dose intervention group showed focal hypertrophic changes, while the thyroid tissue of other hyperthyroidism mice showed diffuse hypertrophic changes. The CD4+CD25+/CD4+Treg ratio in early high-dose intervention group was higher than that in model group at the 10th week (4 weeks after three recombinant adenovirus immunization) (P<0.05). Compared with the model group at the 10th week, the levels of IL-2, IL-12p70 and IFN-γ in the early high-dose intervention group were all decreased (all P<0.05), and the levels of IL-10 were increased (P<0.05). Conclusion: Early high-dose (500 mg·kg-1·d-1) TGP intervention group displays a protective effect against GD mice, the mechanism of which may be related to regulatory T cell function changes and Th1/Th2 cytokine balance restoration.

[Changes of intestinal wall barrier function and its correlation with susceptibility to infection in patients with cirrhotic portal hypertension].

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.

[Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer].

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.

[Measuring laryngotracheal stenosis by extracting centerline based on CT 3D reconstruction].

Objective: To compare the accuracy of the centerline extracted based on CT 3D reconstruction and conventional CT 3D reconstruction in measuring the length and degree of laryngotracheal stenosis. Methods: A retrospective analysis was performed on 35 patients with laryngotracheal stenosis (including 19 cases without tracheotomy and 16 cases with tracheotomy) treated in the Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Guangxi Medical University from March 2006 to March 2016, including 20 males and 15 females, whose ages ranged from 1 to 73 years, with a median age of 40.5 years. And CT data of 20 normal subjects were included in the same period, including 10 males and 10 females, whose ages ranged from 20 to 63 years, with a median age of 37.0 years. The continuous cross-sectional area of the airway perpendicular to the centerline was obtained by Mimics software. The area was compared with the discontinuous cross-sectional areas reconstructed by conventional CT 3D reconstruction software advantage workstation, also the length of cervical trachea, the length of stenosis, and the minimum airway area were compared. Multi-factor linear stepwise regression method was used to analyze the factors influencing the measuring difference between the two methods. Three patients with laryngotracheal stenosis were selected, and the measured stenosis length was compared with the surgical specimens to evaluate the accuracy of the two methods. SPSS 26.0 software was used for statistical analysis. Results: In normal people, the areas of thyroid cartilage notch, glottis, inferio thyroid cartilage margin, inferio cricoid cartilage margin, and suprasternal notch planes measured by Mimics centerline method were smaller than those measured by conventional CT 3D reconstruction (t thyroid cartilage notch=4.685, tglottis=3.791, tlower thyroid cartilage margin=5.621, tlower cricoid cartilage margin=6.312, tsuprasternal notch plane=6.436, P<0.05). And the airway length measured by Mimics centerline method from the inferior thyroid cartilage to the superior sternal notch was longer (t=9.79, P<0.001). In laryngotracheal stenosis, in the non-tracheotomy group, the minimum airway area measured by Mimics centerline method was smaller and the stenosis length was longer than those measured by the conventional CT 3D reconstruction, and the difference was statistically significant (tminimum airway area=2.562, tstenosis length=5.240, P<0.05). In the tracheotomy group, the stenosis length measured by Mimics centerline method was longer than that measured by conventional CT 3D reconstruction, and the difference was statistically significant (tstenosis length=2.854, P<0.05). Multi-factor linear regression analysis showed that different CT thickness had a statistically significant effect on the difference in the length of stenosis measured by the two methods (b=-5.370, t=-3.306, P=0.004), and different tracheal forward angle had a statistically significant effect on the difference in the minimum airway area measured by the two methods (b=-0.419, t=-2.208, P=0.04). The difference between the measured length of the Mimics centerline method and the intraoperative specimens was less than 0.5 mm. Conclusion: The centerline extracted based on CT 3D reconstruction can precisely reflect the laryngotracheal morphology and measure laryngotracheal stenosis more accurately.

[Myxiod pleomorphic liposarcoma: a clinicopathological and molecular genetic analysis of six cases].

Objective: To investigate the clinicopathologic and molecular genetic characteristics of myxoid pleomorphic liposarcoma (MPLPS). Methods: Six cases of MPLPS diagnosed and consulted in Fujian Provincial Hospital from 2015 to 2021 were collected for histomorphological observation, immunohistochemistry, and fluorescence in situ hybridization (FISH) detection of DDIT3 (CHOP) gene translocation and MDM2/CDK4 gene amplification. Results: There were four males and two females, aged 26-74 years (mean 53.8 years). The tumor size was 3.8-16.0 cm (mean 11.8 cm). All six cases had similar histopathologic features, showing overlapping histologic morphology of myxoid liposarcoma and pleomorphic liposarcoma. Four cases (4/6) were positive for S-100 protein, and the Ki-67 index was 50%-95%. All cases (6/6) were negative for DDIT3 (CHOP) translocation and MDM2/CDK4 amplification by FISH. TP53 (p.R248w) germline mutation was found in one case. Conclusions: MPLPS is a rare subtype of liposarcoma, characterized by overlapping morphology of myxoid liposarcoma and pleomorphic liposarcoma. Genetically, a few of them have TP53 gene germline mutations, but they lack of DDIT3 (CHOP) translocation or MDM2/CDK4 amplification.

[Follow-up study of fetal cardiac birth defects after prenatal diagnosis and graded counseling].

Objective: To explore accurate prenatal diagnosis, full-coverage graded counseling and follow-up for the fetus with cardiac birth defects (CBD). Methods: CBD fetus diagnosed prenatal by echocardiography from January 2018 to December 2020 in Guangdong Provincial People's Hospital were enrolled. Fetal CBD was graded (Ⅰ-Ⅵ) according to prognosis and possible operation time after birth, and the classification criteria and common diseases included were proposed. After the prenatal grading counseling, the outcome of the fetus was followed-up. The induced labor rate, live birth rate, prenatal and postnatal ultrasound diagnosis coincidence rate and other indicators were calculated. The disease composition ratio, prognosis of fetus with different grades and the outcome of integrated treatment were analyzed. Results: The detection rate of fetal CBD was up to 16.2% (1 971/12 188), 30 cases of which were excluded. A total of 1 941 cases were included in this study, including 196 cases (10.1%) of gradeⅠ, 433 cases (22.3%) of gradeⅡ, 615 cases (31.7%) of grade Ⅲ, 261 cases (13.4%) of grade Ⅳ, 388 cases (20.0%) of gradeⅤ, 48 cases (2.5%) of grade Ⅵ. Grade Ⅱ and gradeⅢ (the operation time was within 1 year after birth) accounted for 54.0% (1 048/1 941). The distribution of some diseases in different grades had obvious proportion advantage, which was representative. Among 1 747 CBD fetus, 736 cases (induced labor rate 42.1%) chose to terminate pregnancy due to CBD. Of the 1 010 live births, 975 cases (96.5%) had the same prenatal and postnatal diagnosis, 3 cases were missed diagnosis and 32 cases were misdiagnosed. The diagnostic accuracy of live births with severe and complex congenital heart disease was 383 out of 389 (98.5%). A total of 258 cases have received surgery or intervention. The age at the time of surgery or intervention was different among grades（χ²=47.3，P<0.001）. With the improvement of prognosis from gradeⅠ to Ⅴ, the live birth rate increased and the induced labor rate decreased accordingly; the difference between grades was significant（χ²=623.6，P<0.001）. Conclusions: Prenatal diagnosis and graded counseling is important in the integrated model. Fetal CBD grading could refine post-natal treatment strategies, guide delivery decisions and become an evaluation standard.

[Impact of different referral timing on the pregnancy outcomes of severe pre-eclampsia in the referral system].

Objective: To explore the impact of different referral timing on postponing early-onset pre-eclampsia (PE), postponing severe pre-eclampsia (SPE), reducing SPE severe complications and improving maternal and neonatal outcomes by analyzing the pregnancy outcomes of SPE patients who were referred from primary hospitals to tertiary referral center in the referral system. Methods: The clinical data of 159 SPE patients who were referred from primary hospitals, treated and then terminated their pregnancy in Peking University Third Hospital from January 2020 to October 2021, were observed and analyzed in this clinical observational study. According to the clinical stage of PE at the time of referral, they were divided into four groups: 38 cases were referred after onset of SPE severe complications (SPE-C group), 72 cases were referred after onset of SPE (a-SPE group), 15 cases were referred after onset of PE (a-PE group) and 34 cases were referred after detection of PE early warning-signs (Warn-s group). And then these 159 cases were divided into different color groups according to the project management system for high-risk pregnant women. Patients of Red color (highest risk) and Orange color (higher risk) were required to be referred to tertiary hospitals (Red-Orange group, 113 cases), and patients of Yellow color (high risk) could be treated under tertiary hospitals (Yellow group, 46 cases). The maternal and neonatal outcomes of different referral timings were analyzed and compared. Results: (1) Pregnancy outcomes of different referral timings grouped by PE clinical stage at the time of referral: the later the referral timing, the higher the rate of SPE severe complications, the shorter the interval from referral to termination of pregnancy. The rate of SPE severe complications in the SPE-C group was significantly higher than those of the other three groups, and the interval from referral to termination of pregnancy in the SPE-C group was significantly shorter than those of the other three groups (all P<0.05). The referral gestational age of Warn-s group was earlier than those of the other three groups (all P<0.05). The average gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications were all after 34 gestational weeks, and were later than those of a-SPE group and SPE-C group; the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, neonatal intensive care unit (NICU) hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group, and its rate of take-home-babies was 100%, significantly higher than those in a-SPE group and SPE-C group (all P<0.05). The gestational ages for onset of SPE and termination of pregnancy in a-PE group were later than those in a-SPE group and SPE-C group, the rates of SPE onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, and NICU hospitalization were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group (all P<0.05). (2) Pregnancy outcomes of different referral timings grouped by the color classification of PE clinical characteristics: among the 159 cases of SPE, 113 cases (71.1%, 113/159) were in the Red-Orange group which were required to be referred to tertiary hospitals, and 46 cases (28.9%, 46/159) were in the Yellow group,which were not in the range of referral requirements, but actually referred to the tertiary hospital and eventually developed SPE. Gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications in the Yellow group were later than those of the Red-Orange group, while the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, NICU hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of the Red-Orange group, the length of NICU stay was shorter than that of the Red-Orange group, and its rate of take-home-babies was higher than that in the Red-Orange group (all P<0.05). (3) Analysis of different clinical referral timings in the Yellow group: among these 159 SPE patients, 46 cases (28.9%, 46/159) would be excluded from the range of referral requirements which belonged to the Yellow color grade, but 6 cases still developed SPE severe complications (4 cases in Warn-s group and 2 cases in a-PE group), 17 cases were terminated pregnancy before 34 weeks of gestation (12 cases in Warn-s group and 5 cases in a-PE group), and 23 cases developed SPE before 34 weeks of gestation (17 cases in Warn-s group and 6 cases in a-PE group). (4) Multivariate analysis: referral after detection of PE early warning signs was the independent protective factor for postponing the onset of SPE severe complications (P<0.05). Referral after detection of PE early warning signs and referral after onset of PE were both protective factors for postponing the onset of SPE and early-onset PE (all P<0.05). Conclusions: Different referral timing in the referral system is one of the key points that affect the maternal and neonatal outcomes of SPE. Referral after detection of PE early warning signs and timely referral after onset of PE would reduce early-onset PE, postpone the onset of SPE and reduce the severe complications of SPE. The clinical development and evolution of PE is really complicated, and referral based on specific clinical situations is better than referral based on fixed mode.

[Magnetic resonance imaging analysis on the effect of marathon on the dynamic changes of morphological characteristics of patellar tendon in amateur marathon runners after half marathon].

Objective: To explore the dynamic changes of morphological characteristics of patellar tendon (PT) in amateur athletes after a half-marathon using magnetic resonance imaging. Methods: A total of 19 male amateur marathon runners with 38 knee joints,aged from 26 to 53(41.5±7.9) years, running for 3 to 18 years, with a weekly running volume of 30-90 km and a monthly running volume of 100-300 km were enrolled and underwent 1.5T MRI scan before the half-marathon, within 3 hours after running and 3 days after running. Ten healthy male volunteers with 20 knee joints, who had never participated in marathon and exercised (including but not limited to running) per week for less than 150 minutes were recruited as the control group, aged from 26 to 54 (39.4±9.1) years. Firstly, the PT signal was qualitatively assessed on fat-suppressed proton density-weighted imaging (fs-PDWI) sequence to observe the presence of patellar tendinitis. Then, the length, proximal, middle and distal cross-sectional area (CSA), and volume of PT were measured using the post-processing tool ITK-SNAP, and the data were standardized. The independent sample t-test was used for comparing. One-way repeated measures analysis of variance was used to analyze the morphological changes of PT before and after half-marathon running. Results: The incidence of asymptomatic patellar tendinitis in amateur marathon runners was 26.3% (5/19). No significant MR signal changes of PT were observed in all runners after running. The proximal CSA in runners group was larger than that in controls [(4.20±0.62) mm2/kg3/4 vs (3.63±0.57) mm2/kg3/4, P<0.05], and there was no significant difference in length, medium and distal CSA and volume(all P>0.05). The length, proximal and distal CSA and volume of PT in runners group increased at 3 h after running [(47.35±3.22) mm vs (46.83±3.35) mm; (102.52±13.03) mm2 vs (98.98±13.14) mm2; (108.67±15.72) mm2 vs (100.27±14.37) mm2; (4 020.36±514.38) mm3 vs (3 826.57±499.23) mm3, all P<0.05]. There was no significant difference between before running and 3 days after running(all P>0.05). The middle CSA were not significantly different among different periods(all P>0.05). Conclusion: Marathon has effect on the normal PT morphology in male amateur marathon runners, showing an increase in proximal CSA. A half-marathon will cause reversible changes in PT length, regional CSA and volume.

[Diffusion tensor imaging in quantitative evaluation on thigh muscle of male amateur marathon runners after running a half marathon].

Objective: To investigate the effect of half marathon on thigh muscle in male amateur marathon runners by diffusion tensor imaging (DTI). Methods: A total of 17 male amateur marathon runners aged from 27 to 57 (43.7±2.8) years were recruited from May to August 2020 in Hangzhou, Zhejiang Province. MRI examination of bilateral thigh muscles were performed before and 3 h, 3 d and 7 d after a half marathon. The fractional anisotropy (FA) values was obtained by DTI sequence. The FA values of rectus femoris, intermedius femoris, medial femoris, lateral femoris, biceps femoris longus, semitendinosus, semimembranosus, adductor magnus and adductor longus were measured on the horizontal axis of bilateral thigh muscles. Friedman M test was used to compare the changes of FA values of each muscle at each time point before and after running, and pairwise comparison of FA values of statistically significant muscles at 3 h, 3 d and 7 d after running was performed. Results: The overall FA value of thigh muscle group [M (Q1, Q3)] at 3 h after running was decreased compared to before running [0.24 (0.20, 0.28) to 0.25 (0.21, 0.29), P<0.001], and there was no significant difference between baseline values at 3 d and 7 d after running (all P>0.05). FA values of vastus intermedius, vastus medialis, semimembranosus and adductor magnus at 3 h after running were lower than those before running [(0.19 (0.18, 0.22) vs 0.21 (0.19, 0.24), 0.19 (0.17, 0.20) vs 0.21 (0.18, 0.23), 0.26 (0.24), 0.29) vs 0.27 (0.15, 0.30) and 0.20 (0.19, 0.22) vs 0.21 (0.20, 0.23), both P<0.05], and there was no statistical significance between 3 d and 7 d after running and those before running (all P>0.05). FA value of vastus lateralis muscle at 3 h after running decreased compared with that before running, but the difference was not statistically significant (P>0.05). FA value began to increase at 7 d after running, and the difference was statistically significant [0.24 (0.21, 0.27) vs 0.23 (0.19, 0.25), P = 0.002]. FA value of rectus femoris muscle at 3 h after running decreased compared with that before running, but the difference was not statistically significant (P>0.05), and began to increase at 3 d after running and the difference was statistically significant [0.29 (0.26, 0.34) vs 0.26 (0.23, 0.29), P=0.006]. FA value of adductor longus muscle increased at 3 h after running, but the difference was not statistically significant (P>0.05). FA value continued to increase at 3 d and 7 d after running, and the difference was statistically significant [0.23 (0.21, 0.25) vs 0.22 (0.19, 0.24), 0.23 (0.21, 0.26) vs 0.22 (0.19, 0.24), all P<0.05]. Conclusions: The change of FA value of thigh muscle after half marathon is reversible. At 3 h after half marathon, FA values of femoris intermedius, femoris medialis, semimembranosus muscle and adductor magnus muscle of amateur marathon runners decreased most obviously, which may be the dominant muscle group during running.

Thiophene and diaminobenzo- (1,2,5-thiadiazol)- based DAD-type near-infrared fluorescent probe for nitric oxide: A theoretical research.

A near-infrared fluorescent probe (LS-NO) for the real-time detection of nitric oxide (NO) in inflammatory bowel disease (IBD) was developed recently. The probe used oligoglycol morpholine-functionalized thiophene as strong electron donors and diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor and NO trapping group. It could detect exogenous and endogenous NO in the lysosomes of living cells with high sensitivity and specificity. To further understand the fluorescent mechanism and character of the probes LS-NO and LS-TZ (after the reaction of the probe LS-NO with NO), the electron transfer in the excitation and emitting process within the model molecules DAD-NO and DAD-TZ was analyzed in detail under the density functional theory. The calculation results indicated the transformation from diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor to triazolo-benzo-(1,2,5-thiadiazole) as a strong electron acceptor made LS-NO an effective "off-on" near-infrared NO fluorescent probe.

[Clinical characteristics of severe pre-eclampsia in a single tertiary referral center].

Objective: To explore the feasibility and key point of improvement in preventing and postponing the onset of severe pre-eclampsia (SPE) and its severe complications in the tertiary referral system by analyzing the clinical characteristics of SPE in a single tertiary referral center. Methods: The clinical data of 217 patients with SPE who were hospitalized and terminated pregnancy in Peking University Third Hospital from January 2020 to December 2020 were retrospectively analyzed. The risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the characteristics and perinatal outcome. Results: (1) Clinical characteristics: among the 217 cases of SPE, 84 cases were in the referral group and 133 cases were in the central group. The gestational ages at SPE clinical diagnosis [31.5 weeks (28.1-34.6 weeks) vs 35.6 weeks (33.3-37.2 weeks); Z=-6.547, P<0.01], termination of pregnancy [32.3 weeks (29.5- 35.1 weeks) vs 36.3 weeks (34.4-37.5 weeks); Z=-6.554, P<0.01] and onset of SPE severe complications [30.6 weeks (26.4-32.7 weeks) vs 34.9 weeks (32.7-36.5 weeks); Z=-4.040, P<0.01] in the referral group were significantly earlier than those in the central group, the rates of ICU [10.7% (9/84) vs 3.8% (5/133); χ²=4.126, P=0.042] and neonatal ICU hospitalization [72.9% (51/70) vs 54.7% (70/128); χ²=6.286, P=0.012] were higher than those in the central group, while the live birth rate [83.3% (70/84) vs 96.2% (128/133); χ²=10.736, P=0.001] was lower than that of the central group. (2) Analysis of risk factors: for the patient whose risk factors were obesity, advanced age or pre-eclampsia history, the gestational ages at SPE clinical diagnosis and termination of pregnancy in the referral group were significantly earlier than those in the central group (P<0.05). For those with chronic hypertension, the gestational ages at severe complications onset in the referral group were significantly later than those in the central group (P<0.05). For those without obvious risk factors, the gestational ages at SPE clinical diagnosis, termination of pregnancy and onset of SPE severe complications in the referral group were earlier than those in the central group (P<0.05). (3) Analysis of severe complications: the top three severe complications in the referral group and the central group were hypertensive encephalopathy/cerebrovascular accident [20.2% (17/84) vs 7.5% (10/133)], HELLP syndrome [7.1% (6/84) vs 8.3% (11/133)] and placental abruption [8.3% (7/84) vs 7.5% (10/133)]. The rate of hypertensive encephalopathy/cerebrovascular accident in the referral group was significantly higher than that in the central group (χ²=7.645,P=0.006). (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (8.3%, 7/84), referral after onset of SPE (67.9%, 57/84), referral after detection of SPE early warning signs (14.3%, 12/84) and referral after detection of SPE risk factors in the 2nd and 3rd trimester (9.5%, 8/84). The earlier the referral, the longer the interval from clinical diagnosis to onset of severe complications, from referral to termination of pregnancy, and from referral to severe complications onset (P<0.05). The earlier the referral, the lower the NICU hospitalization rates, the higher the live birth rates. The ICU hospitalization rate of referrals after severe complications onset was significantly higher than those of the other three referral timing groups (P<0.05). Conclusions: SPE occurs in hospitals of different levels. Although tertiary referral center may postpone the onset of SPE and its severe complications, reduce the severity of SPE and prolong the gestational age, its awareness of prevention and control still needs to be further improved. Early identification of the risk of SPE and timely referral are important parts of improving SPE adverse outcomes in primary medical institutions. The significance and value of referral system need to be brought into full play.

An evaluation of concordance between head and neck advanced practice radiation therapist and radiation oncologists in toxicity assessment for nasopharyngeal carcinoma patients.

BACKGROUND: Weekly toxicity assessments for patients undergoing head and neck (HN) radiotherapy are essential to ensure that acute side effects are appropriately managed in order for patients to complete their treatment in a safe and timely manner. The incorporation of Advanced Practice Radiation Therapist (APRT) led treatment reviews has been reported for various subsites, but there is currently a lack of published literature regarding this role for patients with HN cancer. The purpose of this study is to assess the concordance of toxicity assessments performed during weekly radiotherapy treatment reviews for patients undergoing HN radiotherapy between the HN APRT and Radiation Oncologist (RO). METHODS: Twenty-three patients with nasopharyngeal cancer (NPC) under the care of 3 ROs were recruited from June to December 2018; weekly assessments were independently performed by HN APRT and ROs. The HN toxicity assessment was graded according to the Common Terminology Criteria for Advanced Events v4.0. Both assessors were blinded to each other's assessments. The percentage agreement of concordance and agreement level were interpreted by Cohen's Kappa statistic (κ), with the ROs' assessments deemed as the 'gold standard'. RESULTS: The overall concordance for all graded toxicity assessments between HN APRT and ROs was 78.4%. Xerostomia, dysgeusia, pharyngeal pain and dermatitis assessment were evaluated as 'Good' with agreement ranging from κ = 0.608-0.640 between the HN APRT and ROs while dysphagia scored an 'Almost Perfect' agreement of κ = 0.834. 'Moderate' agreement between the HN APRT and ROs was observed for oral pain and mucositis assessment. A scoring discrepancy of 1 and 2 grades was observed in 21.2% and 0.4% for these two toxicities. CONCLUSION:  There was high concordance in scoring of acute toxicity between the HN APRT and ROs. The results support the continuing involvement of HN APRT in weekly assessments for NPC patients.

[Evaluation of the effect of free fibular flap transplantation in repairing mandibular osteoradionecrosis defect in 151 cases].

Objective: To investigate the clinical effect of free fibula flap transplantation in repairing the defect of mandibular osteoradionecrosis (ORN). Methods: A total of 151 mandibular ORN patients undergoing free fibular flap transplantation were selected from August 2005 to September 2020 in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among them, 109 patients were males and 42 patients were females, aged (54.1±10.1) (ranged 31-85) years old. The clinical data of the patients was collected and the survival rate of the flaps and postoperative function were calculated to evaluate the surgical efficacy. The χ2 test was used for difference analysis. Results: Among the 151 patients, mandibular ORN caused by radiotherapy for nasopharyngeal carcinoma accounted for 79.5% (120/151). The average time for mandibular ORN appeared was 5(6) years after radiotherapy. Facial artery [57.2%(87/152)] and superior thyroid artery [32.9%(50/152)] were the main anastomotic arteries in the recipient area. There was no significant difference in the necrosis rates of the two flaps [10.3%(9/87) and 12.5% (5/50), respectively, P=0.949]. The main anastomotic veins in the recipient area were the external jugular vein [48.4%(135/279)] and the common facial vein [26.5%(74/279)]. Twenty-five cases (16.6%) had one vein anastomosed, and 126 cases (83.44%) had two veins anastomosed. There was no significant difference in the flap necrosis rate between the two conditions [20.0%(5/25) and 7.1%(9/126), respectively, P=0.100]. Ninety-seven cases (64.2%) used the peroneal musculocutaneous-fascia composite flap to repair the maxillofacial soft and hard tissue defects. Thirteen cases (8.6%) underwent the restorations with digital virtual surgery design, of which 5 cases were repaired with dental implants at the same time. After the operations, lower respiratory tract infection occurred in 17 patients (11.3%), and upper respiratory tract obstruction occurred in 3 cases (2.0%). The survival rate of the flap after operation was 90.7% (136/151), and 21 patients (13.9%) had flap vascular crisis. Delayed healing of maxillofacial wounds occurred in 33 cases (21.9%). After 3 to 24 months of follow-ups, 110 patients (76.9%) had no fistula inside/outside the oral cavity, 118 patients (82.5%) had an improvement in opening mouth of increasing (≥0.5 cm) after surgery, 135 patients (94.4%) had pain relief, 97 cases (67.8%) could eat normal diet, semi-liquid or soft food, and 137 cases (95.8%) were satisfied or basically satisfied with the treatment effects. Conclusions: The free fibular flap transplantation is an effective method to repair mandibular ORN defects. Preoperative vascular assessment is helpful for the selection of recipient vessels. Facial artery, superior thyroid artery, external jugular vein and common facial vein can be used as the main recipient vessels. The repair of the peroneal musculocutaneous-fascia composite flap facilitates the closure of internal and external fistulas. Digital technology can help to restore the maxillofacial shape more accurately, improve the patient's occlusal and chewing function and enhance the quality of life of mandibular ORN patients.

[Research advances on the roles of exosomes derived from vascular endothelial progenitor cells in wound repair].

Angiogenesis is the core step of wound repair, and vascular endothelial progenitor cells (EPC) play an extremely important role during wound repair. Recent studies have shown that vascular EPC-derived exosomes (EPC-Exo) can protect vessels, promote the proliferation and migration of vascular endothelial cells, and have anti-inflammatory, anti-oxidant and anti-apoptotic effects on vascular endothelial cells. This article reviews the mechanism of vascular EPC-Exo in angiogenesis and its potential applications in wound repair in recent years.

[Advances in the research of application of skin-stretching device in wound closure].

Skin-stretching device as a new treatment method of wound closure has been recognized by many discipline fields. Through continuous improvement and adjustment in clinical application, it has achieved remarkable results in some departments. This article summarizes the basic theory, history, classification, and application of skin-stretching devices.

Effects of jugular infusions of isoleucine, leucine, methionine, threonine, and other amino acids on insulin and glucagon concentrations, mammalian target of rapamycin (mTOR) signaling, and lactational performance in goats.

The supply and profile of absorbed AA may affect milk protein synthesis through hormonal changes and mammalian target of rapamycin (mTOR) signaling pathways; and Ile, Leu, Met, and Thr (ILMT) are the 4 AA that have been reported to have the greatest effect on mammary mTOR signaling. The extent to which ILMT and the other remaining AA (RAA) differ in their effects on milk protein synthesis needs to be systematically investigated. In this study, 5 lactating goats, averaging 120 ± 10 d in milk, fitted with jugular vein and carotid artery catheters, were fasted for 24 h, followed by intravenous infusions of a mixture containing AA and glucose for 8 h in a 5 × 5 Latin square design. The AA mixtures were formulated according to the profile of casein. The amounts of AA infused were calculated based on supplies of AA when metabolizable protein (MP) was at requirement (MR). Treatments were an infusate containing glucose without AA (NTAA); an infusate containing 3 × the MR of Ile, Leu, Met and Thr (3F0R); and infusates containing 3F0R plus 1, 2, or 3 × MR of RAA (3F1R, 3F2R, and 3F3R, respectively) according to amounts provided when fed to meet MP requirements for maintenance and lactation for each goat. Milk, arterial blood, and mammary tissue samples were collected immediately after halting the infusion. Relative to NTAA, supplementation of ILMT tended to increase milk protein production and plasma glucose concentrations, and increased milk and lactose production, but had no effects on production or content of milk fat. Graded supplementation of RAA tended to quadratically affect production of milk and lactose. Arterial glucose and glucagon concentrations decreased linearly, and plasma insulin concentrations decreased quadratically with increased RAA. Mammary p70-S6K1 phosphorylation was decreased by addition of ILMT compared with NTAA but increased linearly with increased RAA infusion. Furthermore, EIF4EBP1 gene expression was much lower for 3F-treated goats than for the NTAA treatment. Both MTOR and RPS6KB1 gene expressions were decreased quadratically with increased RAA supply. These results suggested that short-term milk protein yield tended to be increased by elevated ILMT availability, and this trend was not explained by variations in mammary mTOR signaling or pancreatic hormone secretions, whereas graded increase of RAA in combination with ILMT appeared to regulate the efficiency of conversion of glucose to lactose in a manner not involving milk protein production.

Effects of rumen-protected methionine and other essential amino acid supplementation on milk and milk component yields in lactating Holstein cows.

Objectives of this study were to investigate the effects of supplementing rumen-protected methionine (RP-Met), threonine (RP-Thr), isoleucine (RP-Ile), and leucine (RP-Leu) individually or jointly to a low-protein diet, on the performance of lactating dairy cows, as well as to determine the effects of these amino acids (AA) on the mammalian target of rapamycin (mTOR) in vivo. Ten lactating Holstein cows were randomly allocated to a repeated 5 × 5 Latin square experiment with five 19-d periods. Treatments were high-protein diet (16% crude protein, positive control; HP), low-protein diet (12% crude protein, negative control; LP), LP plus RP-Met (LPM), LP plus RP-Met and RP-Thr (LPMT), and LP plus RP-Met, RP-Thr, RP-Ile, and RP-Leu (LPMTIL). The dry matter intakes (DMI) of the LP, LPM, and LPMT diets were lower than that of the HP diet, whereas the DMI of the LPMTIL diet was intermediate between the HP diet and the other LP diets. Supplementing RP-Met to the LP diet increased the yields of milk and milk protein, increased the content of milk urea N, and tended to increase milk N efficiency. Co-supplementation of RP-Thr with RP-Met resulted in no further milk production increase. Co-supplementation of all 4 rumen-protected amino acids (RP-AA) increased milk and lactose yields to the level of the HP diet and tended to increase milk protein yield compared with the LPMT diet. We found no significant differences in the contents and yields of milk components between the LPMTIL and HP diets except for a lower milk urea N content in the LPMTIL diet. Venous concentrations of the measured AA were similar across the LP and LP diets supplemented with RP-AA. Relative to levels of the HP diet, LP diets had higher venous concentrations of Met and Gly and tended to have higher Phe concentration and lower concentrations of Val and BCAA. The LPMTIL diet had higher venous concentrations of Arg, Lys, Met, Phe, and Glu, and a lower Val concentration. Phosphorylation status of the measured mTOR components in LPM and LPMT treatments were similar to those in the LP treatment but phosphorylation status of mTOR and eIF4E-binding protein 1 (4eBP1) in LPMTIL treatment were higher. The phosphorylation rates of eukaryotic elongation factor 2 (eEF2) in the 4 LP and LP plus RP-AA diets were higher than that of the HP diet. Overall, results of the present study supported the concept that under the relatively short time of this experiment, supplementing RP-AA, which are believed to stimulate the mTOR signal pathway, can lead to increased milk protein yield. This increase appears to be due to increased DMI, greater mTOR signaling, and greater eEF2 activity.