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Purpose@#The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV). @*Methods@#This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)—normal BP (NBP): SBP 0.05). However, the NBP group had a notably lower PWV-ES than the PHT (P0.05). @*Conclusion@#Carotid morphological and biomechanical properties in the PHT group differed from those in the NBP group. ufPWV could be used for an early evaluation of carotid stiffening linked to pre-hypertension.
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The composition of intestinal microflora is closely related to the occurrence and development of colorectal cancer (CRC). Among them, Fusobacterium nucleatum (Fn) has been proved directly related to the recurrence, metastasis and chemotherapy resistance of CRC. Therefore, it is of great significance for the prevention and treatment of colorectal cancer by the exploration potential anti-Fn drug targets and discovery small molecule drugs. However, no selective anti-Fn small molecule inhibitors have been reported so far as well as their anti-Fn thereby "anti-Fn further anticancer" mechanisms are unclear. Herein, this article reviews the potential therapeutic targets and small molecule ligands of Fn in order to provide a reference for the development of anti-Fn and anti-CRC small molecule drugs.
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Drug-induced liver injury (DILI) is one of the common clinical adverse drug reactions and remains a major cause of drug restriction, development termination and withdrawal from the pharmaceutical market today. In recent years, a variety of chemical components and metabolites of traditional Chinese medicine (TCM), as well as the endogenous effector substances influenced by metabolism of both, have attracted much attention for their significant hepatoprotective activities. However, the mechanism of TCM against DILI is complex, the related effector substances are still unclear, and its metabolism-related studies are still relatively weak. Therefore, this review summarized the mechanisms of DILI and its treatment by TCM from the perspective of metabolism, and for the first time, innovatively classified the Chinese medicine effector substances into two categories: exogenous (active components and metabolites of TCM) and endogenous (intestinal probiotics and endogenous metabolites), in order to reduce the occurrence of DILI, explore and develop effective anti-drug-induced liver injury effector substances of TCM, and further develop clinical drugs with hepatoprotective effects.
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Objective:To compare the clinical efficacy of bundle suture and Krackow suture in the treatment of acute closed Achilles tendon rupture.Methods:A retrospective cohort study was used to analyze the clinical data of 58 patients with acute closed Achilles tendon rupture admitted to Tongji Hospital of Tongji University from August 2014 to August 2021, including 53 males and 5 females, aged 27-55 years [(39.6±7.1)years]. The patients were treated with open repair and were assigned to bundle suture group ( n=30) and Krackow suture group ( n=28). The incision length and operative time were compared between the two groups. The healing of the Achilles tendon was observed. The difference in circumference between the affected and healthy side of the calf, ratio of width to anterior-posterior diameter at the cross-sectional area of Achilles tendon rupture, and ratio of scar tissue to tendinous fibrous tissue at the cross-sectional area of Achilles tendon rupture were measured at 12 months after surgery. At the same time, the complete Achilles tendon rupture score (ATRS) and American Foot and Ankle Surgery Society (AOFAS) ankle-hindfoot score were performed. The occurrence of complications was observed at follow-up. Results:All patients were followed up for 12-28 months [(17.9±4.2)months]. The incision length and operative time in bundle suture group [6.0(4.5, 9.0)cm, 77.5(60.0, 95.0)minutes] were significantly shorter or longer than those in Krackow suture group [8.0(7.0, 11.0)cm, 68.5(55.0, 86.0)minutes] (all P<0.01). After 3 months, healing of the Achilles tendon was obtained in both groups. After 12 months, the difference in circumference between the affected and healthy side of the calf was (2.0±0.9)cm in bundle suture group and was (1.9±0.9)cm in Krackow suture group ( P>0.05); the ratio of width to anterior-posterior diameter at the cross-sectional area of Achilles tendon rupture was 1.42±0.20 in bundle suture group, significantly greater than 1.27±0.16 in Krackow suture group ( P<0.01); the ratio of scar tissue to tendinous fibrous tissue at the cross-sectional area of Achilles tendon rupture was 8.6%(6.0%, 24.0%) in bundle suture group, significantly lower than 11.9%(9.0%, 33.0%) in Krackow suture group ( P<0.01); the ATRS and AOFAS ankle-hindfoot score were 91.5(80.0, 99.0)points and 93.0(82.0, 100)points in bundle suture group, similar to 89.0(75.0, 99.0)points and 91.5(77.0, 99.0)points in Krackow suture group (all P>0.05). During the follow-up period, the occurrence of complications were not significantly different between bundle suture group [no deep infection, early Achilles tendon rerupture in 2 patients (7%) ] and Krackow suture group [deep infection in 1 patient (4%), early Achilles tendon rerupture in 1 patient (4%)] (all P>0.05). Conclusions:Both bundle suture and Krackow suture can achieve satisfactory clinical efficacy in the treatment of acute closed Achilles tendon rupture. However, the bundle suture is more conducive to restoring normal anatomical shape of the Achilles tendon and reducing scar formation at the end of the Achilles tendon rupture.
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A clinical data, laboratory examination, genetic test results, diagnose and treatment of a patient with 46, XY disorders of sexual development (46, XY DSD) from a family of the Asp-Glu-Ala-His-box helicase 37 ( DHX37) gene mutation were retrospectively analyzed.The child was admitted in the Department of Genetics, Endocrinology and Metabolism, Jiangxi Children′s Hospital in June 2021.The DHX37 gene mutation was confirmed as a new pathogenic gene leading to 46, XY DSD in 2019.It is featured as autosomal dominant inheritance with incomplete externality.Its clinical manifestations are abnormal external genitalia, testicular degeneration insufficiency syndrome and gonadal insufficiency.This patient is the first 46, XY DSD case caused by the heterozygous variation of DHX37 gene c. 2020C>T (p.R674W) in China.This study can provide new ideas for diagnosis and treatment of 46, XY DSD children and reliable genetic evidence for family reproduction.
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A clinical data, laboratory examination, genetic test results, diagnose and treatment of a patient with 46, XY disorders of sexual development (46, XY DSD) from a family of the Asp-Glu-Ala-His-box helicase 37 ( DHX37) gene mutation were retrospectively analyzed.The child was admitted in the Department of Genetics, Endocrinology and Metabolism, Jiangxi Children′s Hospital in June 2021.The DHX37 gene mutation was confirmed as a new pathogenic gene leading to 46, XY DSD in 2019.It is featured as autosomal dominant inheritance with incomplete externality.Its clinical manifestations are abnormal external genitalia, testicular degeneration insufficiency syndrome and gonadal insufficiency.This patient is the first 46, XY DSD case caused by the heterozygous variation of DHX37 gene c. 2020C>T (p.R674W) in China.This study can provide new ideas for diagnosis and treatment of 46, XY DSD children and reliable genetic evidence for family reproduction.
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The clinical data of rare hemiaxial limb skeletal Ollier disease in a child admitted to the Affiliated Hospital of Zunyi Medical University in July 2020 were analyzed retrospectively.The literature was reviewed and the methods of diagnosis and treatment of Ollier disease in children were summarized.The patient is a 3-year-old boy, who was hospitalized for 2 days of claudication of the right lower limb.Imaging examination showed hemiaxial limb ske-letal disease and suggested the possibility of histiocytosis.Curettage, bone graft and plaster external fixation were performed on the lesions of the right femoral neck and greater trochanter.The postoperative pathological results indicated endogenous chondroma.The follow-up results revealed that the bone graft healed well, the symptoms of claudication were improved, and there were no complications such as infections and femoral head necrosis.Long tubular bones are the main site of children′s Ollier disease, but multiple lesions in hemiaxial limbs are extremely rare.It is difficult to diagnose this rare case, which is easily misdiagnosed.At present, it′s diagnosis still needs to be confirmed by pathological examination.Surgical treatment and long-term follow-up are needed for children with a wide range of lesions, seriously impaired limb function and obvious limb deformity.
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BACKGROUND@#Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals.@*OBJECTIVE@#To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output.@*MAIN OUTCOME MEASURES@#The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA.@*RESULTS@#Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05).@*CONCLUSION@#Low-level LA gradually reduced older patients' postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care.@*TRIAL REGISTRATION@#ClinicalTrials.gov registration number NCT03995446.
Subject(s)
Acupuncture Therapy , Aged , Analgesics, Opioid/therapeutic use , Arthroplasty, Replacement, Knee/adverse effects , Double-Blind Method , Humans , Morphine/therapeutic use , Pain, Postoperative/drug therapy , Single-Blind MethodABSTRACT
Objective:To investigate the risk factors of hyperglycemia during pregnancy and its correlation with adverse pregnancy outcomes based on the retrospective analysis of glucose metabolism of pregnant women in Chongming area.Methods:A total of 604 singleton pregnant women who underwent prenatal examination and delivered normally in the Chongming branch of Xinhua Hospital from September 2019 to May 2021 were enrolled in the study. All subjects were divided into normal glucose tolerance gestation (NGTG) group and gestational diabetes mellitus (GDM) group. Pregnant women whose blood glucose exceeded normal but did not meet the diagnostic criteria of GDM were classified into the intermediate state gestational blood glucose (ISGBG) group. Questionnaire, physical examination, and relevant laboratory tests were completed. Data were analyzed using the Statistical Product and Service Solutions 13.0 (SPSS, Chicago, IL).Results:The incidence rate of GDM was 20.86% (126/604), ISGBG was 40.39% (244/604), and NGTG was 38.74% (234/604) in 604 pregnant women. Multivariate logistic regression analysis showed that gestational age ( OR=1.092, P<0.001), serum triglyceride ( OR=1.625, P=0.001) and free T 3 levels ( OR=1.995, P=0.002) were independent risk factors for GDM. The incidence of pregnancy-induced hypertension, cesarean section, macrosomia, the total incidence of adverse pregnancy outcomes and fetal birth weight in ISGBG and GDM were significantly higher than those in NGTG ( P<0.05 or P<0.01). Conclusion:The incidence of GDM in Chongming area is high, especially higher in that of ISGBG. As both GDM and ISGBG lead to increased adverse pregnancy outcomes, early monitoring should be paid more attention to pregnant women in ISGBG in addition to the early intervention of GDM.
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Objective To investigate the effect of liver CD8 + T lymphocytes on co-cultured hepatic stellate cells (HSCs) after the application of Fuzheng Huayu prescription in a moues model of acute liver injury, as well as the mechanism of action of Fuzheng Huayu prescription in preventing liver fibrosis. Methods A total of 18 specific pathogen-free male C57BL/6NCrl Vr mice were randomly divided into normal group, model group, and Fuzheng Huayu prescription group, with 6 mice in each group. The mice in the Fuzheng Huayu prescription group were given Fuzheng Huayu prescription for 5 days in advance. At 12 hours before the experiment, 10% CCl 4 was injected intraperitoneally at a dose of 2 mL/kg body weight. Blood was collected from the main abdominal vein, and the serum was separated to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Part of the liver was used for pathological observation. After the mice were pretreated with medication in vivo, flow cytometry was used for the sorting of mouse liver CD8 + T lymphocytes, which were then co-cultured with the mouse HSC cell line (JS 1) in a 96-well plate at a ratio of 2∶ 1, and after co-culture for 24 and 48 hours, qPCR was used to measure the changes in the mRNA expression of Col.I and α-SMA. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the SNK- q test or the least significant difference t -test was used for further comparison between two groups. Results The model group had significantly higher activities of ALT and AST than the normal group (both P < 0.000 1), and compared with the model group, the Fuzheng Huayu prescription group had a significantly lower degree of increase in ALT activity ( P < 0.001). HE staining showed that the Fuzheng Huayu prescription group had a significantly lower degree of hepatocyte degeneration and necrosis compared with the model group. Compared with the normal group, the total lymphocytes, CD45, CD4 - CD8 + T and CD8 + CD28 - T in the model group increased significantly, while the proportion of the above lymphocytes in the Fuzheng Huayu formula group decreased significantly compared with the model group ( P < 0.001). CD8 + T lymphocytes isolated from the liver of mice in each group were co-cultured with JS 1 for 48 hours, and compared with the control group (JS 1 cultured alone) and the normal group, the model group had a significant increase in the mRNA expression of α-SMA (both P < 0.01) and significantly higher mRNA expression of Col.I than the control group and the normal group (normal mouse liver CD8 + T lymphocytes co-cultured with JS 1) (both P < 0.001). The Fuzheng Huayu prescription group had significantly lower mRNA expression levels of α-SMA and Col.I than the model group (both P < 0.01). Conclusion Fuzheng Huayu prescription can indirectly inhibit activated HSCs by altering the functional phenotype of CD8 + T lymphocytes in mouse liver.
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Vaccination is one of the most effective intervention for the containment and elimination of infectious diseases. Recently, the world’s first malaria vaccine RTS, S/AS01 was approved by WHO for use among children living in moderately and highly malaria endemic areas of Africa, which brings a hope for the research and development of malaria vaccines. Here, we review the current status of malaria vaccines development and provide a perspective on the development of next-generation malaria vaccines, so as to provide insights into the successful development of malaria vaccines.
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Objective:To analyze the correlation between the posterior malleolus fracture and fixation and the rotational stability of the ankle and to explore the surgical indications for posterior malleolus fracture aiming to provide the theories for the diagnosis and treatment of disorder.Methods:Twenty fresh frozen cadaver specimens were selected. Further, the extent of the tibial insertion of the posterior inferior tibiofibular ligament (PITFL) and inferior transverse tibiofibular ligament (ITTFL) complex was dissected and measured. Based on the tibial insertion of the ligament complex, the model for the supination-external rotation degree 3 ankle fracture with a posterior malleolar fragment and syndesmosis diastasis was created. Moreover, the area threshold of the posterior tibial insertion of posterior malleolus fracture was biomechanically assessed. The difference of the antirotating ability of the ankle-stiffness between simple posterior malleolus fixation and simple syndesmotic fixation was analyzed statistically.Results:The PITFL and ITTFL were presented in all specimens with relatively broad in PITFL tibial insertion. The PITFL was attached to the posterolateral tibia. The distance between the highest point of the tibial insertion and the articular line was 45.2±5.6 mm, while the ITTFL was attached to the posterior distal tibia. The distance between the highest point of the tibial insertion and the articular line was 5.5±1.0 mm. The width of the tibial insertion of the PITFL and ITTFL complex decreased as the distance from the joint line increased. Biomechanical analysis showed that the threshold of posterior area of posterior malleolus fracture was 1/4S. The stiffnesses of posterior malleolus fixation and syndesmosis stabilization were 0.264±0.080 N·m/° and 0.164 ± 0.061 N·m/°, respectively. The percentage of stiffness restored by posterior ankle fixation was 60.9%±10.2%, which was greater than that by syndesmosis stabilization 37.5%±7.9% ( t=17.09, P<0.001) . Conclusion:The surgical technique for posterior malleolus fracture should consider restoration of the axial and rotational stability of the ankle simultaneously. Posterior malleolus fracture fixation is recommended when the syndesmosis is unstable with the area ratio of posterior tibial insertion of posterior malleolus fracture greater than or equal to 1/4. Syndesmotic fixation is proposed to restore and maintain the rotational stability of the ankle when the syndesmosis is unstable with the area ratio less than 1/4. Regardless of the area ratio, the surgical indications for stable syndesmosis depend on the impact of the posterior malleolus fracture on the axial stability of tibiotalar joint, on the involved articular surface area and on the displacement degree of posterior malleolus fragment.
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Objective:To investigate the effects of nedaplatin combined with docetaxel on serum tumor markers and T lymphocyte subsets in patients with epithelial ovarian cancer.Methods:Ninety-two patients with epithelial ovarian cancer who received treatment from March 2016 to December 2017 were included in this study. They were randomly assigned to undergo nedaplatin combined with docetaxel (observation group, n = 46) or cisplatin combined with paclitaxel (control group, n = 46). Both groups received two 21-day courses of treatment. Serum tumor marker level, T lymphocyte subset level, clinical efficacy, incidence of adverse reactions, and 2-year survival rate were compared between the two groups. Results:After treatment, serum cancer antigen 125 (CA125), cancer antigen 199 (CA199), and carcinoembryonic antigen (CEA) levels were (45.84 ± 22.46) U/mL, (35.13 ± 15.03) U/mL, (16.21 ± 3.20) U/mL, respectively in the control group and they were (28.33 ± 20.11) U/mL, (14.82 ± 10.11) U/mL, (5.16 ± 1.33) U/mL, respectively in the observation group. After treatment, CA125, CA199, and CEA levels in each group were significantly decreased compared with before treatment. After treatment, CA125, CA199, and CEA levels were significantly lower in the observation group than in the control group ( t = 3.94, 7.61, 21.63, all P < 0.05). After treatment, the numbers of CD3 +, CD4 +, CD8 + cells in the control group were (16.22 ± 3.12)%, (15.20 ± 1.46)%, (29.21 ± 5.17)%, respectively, and they were (31.22 ± 4.11)%, (24.99 ± 1.71)%, (24.25 ± 4.45)% respectively in the observation group. After treatment, the numbers of CD3 + and CD4 + cells in the observation group were significantly higher than those in the control group ( t = 19.72, 29.53, both P < 0.05). After treatment, the number of CD8 + cells in the observation group was significantly lower than that in the control group ( t = 4.93, P < 0.05). Total response rate was significantly higher in the observation group than in the control group [78.26% (36/46) vs. 58.70% (27/46), χ2 = 4.08, P < 0.05]. The incidence of adverse reactions was significantly lower in the observation group than in the control group [23.91% (11/46) vs. 45.65% (21/46), χ2 = 4.79, P < 0.05]. The 2-year survival rate was significantly higher in the observation group than in the control group [43.48% (20/46) vs. 23.91% (11/46), χ2 = 3.94, P < 0.05]. Conclusion:Nedaplatin combined with docetaxel is highly effective on epithelial ovarian cancer. The combined therapy can greatly reduce serum CA125, CA199, and CEA levels but has no great effects on T lymphocyte subsets. It can increase the survival rate but has no serious adverse reactions.
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Objective:This study was aimed to explore the associations between the risk of dental fluorosis and the serum biomarkers of bone metabolism in children.Methods:A total of 502 children aged 7 - 12 years were selected by cluster sampling from 4 primary schools in Tongxu County, Kaifeng City, Henan Province from April to May 2017. Morning urine and fasting peripheral blood samples were collected from each participant. Urinary fluoride concentration was determined by fluoride ion selective electrode method. Serum calcium, phosphorus, alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), calcitonin (CT) and parathyroid hormone (PTH) levels were measured using an automatic biochemical analyzer. Dean method was used to evaluate the prevalence of dental fluorosis in children, and the participants were divided into dental fluorosis group ( n = 173) and control group ( n = 329) after being diagnosed by trained physicians for their dental fluorosis. The associations between the risk of dental fluorosis and the serum biomarkers of bone metabolism in children were analyzed by logistic regression. Results:The levels of serum phosphorus (mmol/L: 1.54 ± 0.19 vs 1.58 ± 0.21) and OC (ng/ml: 11.59 ± 5.22 vs 12.78 ± 5.88) in children in dental fluorosis group were significantly lower than those in children in control group ( P < 0.05). Logistic regression analysis showed that serum OC level affected the risk of dental fluorosis [odds ratio ( OR) = 0.96, 95% confidence interval ( CI): 0.92 - 0.99, P < 0.05]. The relative contribution of the biomarkers of bone metabolism to the risk of dental fluorosis in descending order were serum OC (36.34%), phosphorus (25.89%), BALP (13.16%), PTH (9.73%), calcium (9.44%), CT (3.72%) and ALP (1.72%). Conclusions:The prevalence of dental fluorosis in children is related to the changes of serum biomarkers of bone metabolism. Serum OC plays an important role in the occurrence of dental fluorosis.
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Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.
Subject(s)
Aged , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Multiple Myeloma/drug therapy , Retrospective Studies , Transplantation, Autologous/methods , Treatment OutcomeABSTRACT
Purpose@#The present study investigated the association between Systematic COronary Risk Evaluation (SCORE)-estimated cardiovascular risk and carotid stiffening in a middle-aged population using ultrafast pulse wave velocity (ufPWV). @*Methods@#This study enrolled 683 participants without known cardiovascular disease or diabetes mellitus who underwent ufPWV measurements. Clinical interviews, physical examinations, laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity (PWV) at the beginning of systole (PWV-BS), and PWV at the end of systole (PWV-ES) were assessed. Each participant underwent an assessment of SCORE risk based on major cardiovascular risk factors (CVRFs), including age, sex, smoking, systolic blood pressure (SBP), and total cholesterol (TC). Crude and adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression were used. Overall CVRFs were adjusted to assess ORs. @*Results@#cIMT and carotid stiffening in PWV-BS and PWV-ES were significantly different between sex subgroups (all P0.05). @*Conclusion@#Carotid stiffening quantified by ufPWV is linked to SCORE categories, and elevated PWV-ES may aid in cardiovascular risk stratification.
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OBJECTIVE@#To explore the contribution of ferroptosis to myocardial injury in mouse models of sepsis and the role lipocalin-2 (Lcn2) in ferroptosis.@*METHODS@#Adult male C57BL/6 mice were randomized equally into sham-operated group, cecal ligation and puncture (CLP)-induced sepsis group, and CLP + Fer-1 group where the mice received intraperitoneal injection of 5 mg/mL Fer-1 (5 mg/kg) 1 h before CLP. The left ventricular functions (including LVEF%, LVFS%, LVIDd and LVIDs) of the mice were assessed by echocardiography at 24 h after CLP. Myocardial injury in the mice was observed with HE staining, and the changes of myocardial ultrastructure and mitochondria were observed using transmission electron microscopy (TEM). Serum TNF-α level was measured with ELISA, and the changes of myocardial iron content were detected using tissue iron kit. The protein expressions of myocardial Lcn2, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) were determined with Western blotting.@*RESULTS@#The septic mice showed significantly decreased LVEF%, LVFS% and LVIDd and increased LVIDs at 24 h after CLP (P < 0.05), and these changes were significantly improved by Fer-1 treatment. Sepsis caused obvious myocardial pathologies and changes in myocardial ultrastructure and mitochondria, which were significantly improved by Fer-1 treatment. Fer-1 treatment also significantly ameliorated sepsis-induced elevations of serum TNF-α level, myocardial tissue iron content, and Lcn2 protein expression and the reduction of GPX4 and FSP1 protein expression levels (P < 0.05).@*CONCLUSION@#GPX4- and FSP1-mediated ferroptosis are involved in myocardial injury in mice with CLP-induced sepsis, and inhibition of ferroptosis can attenuate septic myocardial injury, in which Lcn2 may play a role.
Subject(s)
Animals , Ferroptosis , Heart Injuries , Lipocalin-2 , Male , Mice , Mice, Inbred C57BL , Sepsis/metabolismABSTRACT
Objective: To summarize and analyze the clinical characteristics and gene mutations of 6 patients with Wiedemann-Steiner syndrome (WDSTS). Methods: To review and analyze the clinical data, including general conditions, clinical manifestations, growth hormone, cranial or pituitary gland magnetic resonance imaging (MRI),gene results and other data, 6 cases with WDSTS admitted to the Department of Endocrinology, Genetics and Metabolism of Jiangxi Provincial Children's Hospital and the Department of Child Care of Pingxiang Maternity and Child Care from April 2017 to February 2021 were recruited. Results: Of the 6 patients, 2 were male and 4 were female. The age of the first visit ranged from 1.0 to 11.2 years. All the 6 children presented with growth retardation and mental retardation and they all had typical facial dysmorphism and hypertrichosis (mainly on the back and limbs). Among them, case 5 had a growth hormone deficiency, and case 2 and 4 had abnormalities revealed by cranial MRI. Variations in KMT2A gene were identified in these 6 patients: c.10900+2T>C,c.10837C>T(p.Gln3613*), c.4332G>A(p.E1444E), c.2508dupC(p.W838Lfs*9), c.11695_11696delinsT(p.T3899Sfs*73), c.9915dupA (p.P3306Tfs*22).Among these variations, c.4332G>A, c.11695_11696delinsT and c.9915dupA were novel mutations. Therefore, the final diagnosis of these patients was WDSTS. Conclusions: Patients presented with short stature and mental retardation, typical facial dysmorphism and hypertrichosis should be considered WDSTS. Whole-exome sequencing plays an important role in disease diagnosis and genetic counseling.
Subject(s)
Abnormalities, Multiple , Child , Child, Preschool , Craniofacial Abnormalities , Female , Growth Disorders/genetics , Histone-Lysine N-Methyltransferase , Humans , Hypertrichosis/genetics , Infant , Intellectual Disability/genetics , Male , Myeloid-Lymphoid Leukemia Protein , Pregnancy , SyndromeABSTRACT
Objectives@#It is unclear whether G protein-coupled receptor 61 (GPR61) affecting body weight, plays a role in the association between birth weight and weather. This study aimed to assess the effects of prenatal weather and GPR61 on birth weight.@*Methods@#A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during 2011-2012. We detected the maternal and neonatal GPR61 promoter methylation levels, and obtained meteorological and air pollution data.@*Results@#A positive association was observed between maternal and neonatal GPR61 methylation levels, and both of them were affected by precipitation, relative humidity (RH) and daily temperature range (DTR). Birth weight was associated negatively with RH and positively with DTR ( P < 0.05). A significant association was observed between birth weight and neonatal GPR61 methylation. We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight ( P interaction < 0.10), while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight ( P < 0.05).@*Conclusions@#Our findings revealed the significant associations among prenatal weather, GPR61 methylation and birth weight. Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions, while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight.
Subject(s)
Air Pollution/analysis , Birth Weight , Female , Humans , Infant, Newborn , Nerve Tissue Proteins , Pregnancy , Receptors, G-Protein-Coupled/metabolism , Temperature , WeatherABSTRACT
OBJECTIVE@#To observe the effect on motor function, spasticity degree, muscle strength and the relevant parameters of three-dimensional gait analysis in the patients with post-stroke spasticity in the lower limbs treated with the combined therapy of electroacupuncture (EA) and muscle electricity biofeedback or the simple muscle electricity biofeedback therapy on the base of rehabilitation medicine.@*METHODS@#A total of 60 patients with post-stroke spasticity in the lower limbs were randomized into an EA + biofeedback group, a biofeedback group and a rehabilitation group, 20 cases in each one. In the rehabilitation group, the basic rehabilitation training was provided, 45 min each time. In the biofeedback group, on the base of the treatment as the rehabilitation group, the biofeedback therapy was added, 30 min each time. In the EA + biofeedback group, besides the treatment as the biofeedback group, acupuncture was supplemented at Futu (ST 32), Liangqiu (ST 34), Zusanli (ST 36) and Fenglong (ST 40), etc, and EA was applid at Zusanli (ST 36) and Taichong (LR 3) with continuous wave and 5 Hz in frequency. In each group, the treatment was given once daily, 5 times a week, for 6 weeks totally. Separately, before and after treatment, the score of Fugle-Meyer assessment (FMA), the score of clinical spasticity index (CSI) in the lower limbs and the strength of the anterior tibial muscle on the affected side were assessed, and the spatial-temporal parameters (step frequency and steep speed) in the three-dimensional gait analysis and the kinematic parameters (maximum dorsal flexion and maximum plantar flexion of ankle joint on the affected side) were measured in the patients of three groups.@*RESULTS@#After treatment, FMA score was increased as compared with that before treatment in all of three groups (P<0.05). FMA score in the EA + biofeedback group and the biofeedback group was higher than the rehabilitation group respectively (P<0.05). CSI score in the EA + biofeedback group and the biofeedback group was lower than that before treatment respectively (P<0.05), and lower than the rehabilitation group (P<0.05). After treatment, the step frequency and speed were all improved and the angles of maximum dorsal flexion and maximum plantar flexion of ankle joint on the affected side were all increased as compared with those before treatment in the patients of three groups separately (P<0.05). The step frequency and speed, as well as the angles of maximum dorsal flexion and maximum plantar flexion of ankle joint on the affected side in either the EA + biofeedback group or the biofeedback group were all higher than the rehabilitation group (P<0.05), and the step speed in the EA + biofeedback group was higher than the biofeedback group (P<0.05). After treatment, the strength of the anterior tibial muscle on the affected side was increased as compared with that before treatment in the patients of each group (P<0.05); and the strength of the anterior tibial muscle in the EA + biofeedback group and the biofeedback group was larger than the rehabilitation group (P<0.05).@*CONCLUSION@#On the base of rehabilitation treatment, the combined regimen of EA and muscle electricity biofeedback therapy and the simple muscle electricity biofeedback therapy all effectively strengthen the motor functions and reduce spasticity as well as improve step frequency, step speed and the range of motion of ankle joint in the patients with post-stroke spasticity in the lower limbs. Regarding the gait improvement, the combined regimen of EA and muscle electricity biofeedback is better than the simple muscle electricity biofeedback.