BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

ObjectiveTo explore the intervention effect and mechanism of Buzhong Yiqiwan （BZYQ） on colitis mice. MethodSixty-four C57BL/6 mice were randomly divided into 2 weeks blank group， 2 weeks model group， 2 weeks high-dose BZYQ （12 g·kg^-1） group， 2 weeks low-dose BZYQ （6 g·kg^-1） group， 4 weeks blank group， 4 weeks model group， 4 weeks high-dose BZYQ （12 g·kg^-1） group， and 4 weeks low-dose BZYQ （6 g·kg^-1） group. The colitis model was induced in mice by feeding 3% dextran sodium sulfate （DSS） for 7 days. The mice received BZYQ （12 and 6 g·kg^-1） by gavage on the 8^th day after modeling， once per day， and sacrificed on the 2^nd and 4^th weeks， correspondingly. The colon length and weight of mice in each group were measured. Hematoxylin-eosin （HE） staining was used for pathological observation and colonic mucosal inflammation was scored. The mRNA and protein expression of NOD-like receptor thermoprotein domain 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and cysteinyl aspartate-specific protease-1 （Caspase-1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of inflammatory cytokines， such as interleukin （IL）-1β， IL-18， and IL-33 in colonic tissues. ResultCompared with the 2 weeks blank group， the 2 weeks model group showed shortened colon length， increased colon weight （P<0.05）， loss of epithelial cells， destruction of gland structure， infiltration of a large number of inflammatory cells in mucosa and submucosa， local crypt abscess， and increase in mucosal inflammation score （P<0.01） as revealed by light microscopy， elevated levels of IL-1β， IL-18， and IL-33 in colonic tissues （P<0.05）， and increased mRNA and protein expression of NLRP3， ASC， and Caspase-1 （P<0.05）. The intervention of BZYQ （12 g·kg^-1） restored colon length， alleviated mucosal injury （P<0.05）， down-regulated the content of IL-18 （P<0.05）， reduced the mRNA expression of NLRP3 and ASC as well as the protein expression of ASC and Caspase-1 compared with the conditions in the 2 weeks model group. Compared with the 4 weeks blank group， the 4 weeks model group showed decreased colon length， increased colon weight （P<0.05）， decreased glands in the mucosal layer， expansion of glandular cavity， atrophy of crypt， local connective tissue hyperplasia and lymphocyte infiltration， increased inflammation score （P<0.01） as revealed by the light microscopy， increased expression of IL-1β， IL-18， and IL-33 （P<0.05）， and elevated mRNA and expression of NLRP3 inflammasome complex （P<0.05）. Compared with the conditions in the 4 weeks model group， the intervention of BZYQ （12 and 6 g·kg^-1） could improve colon length and weight （P<0.05）， and the intervention of BZYQ （12 g·kg^-1） could also improve the inflammation score of the colon （P<0.05）. Different from the acute stage， the intervention of BZYQ （12 and 6 g·kg^-1） increased the content of IL-33 in the intestinal mucosa and up-regulated the mRNA and protein expression of NLRP3 inflammasome complexes ASC and Caspase-1 （P<0.05）. ConclusionBZYQ can relieve the injury of colitis induced by DSS in mice. The mechanism is related to the regulation of intestinal immune response mediated by NLRP3 inflammasome， and it has different regulatory effects in acute and chronic inflammation stages.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Recently, accumulating evidence suggests that high bilirubin level is involved in the pathophysiology of schizophrenia. High bilirubin level during early childhood may increase the risk of being suffered from schizophrenia after adulthood, and schizophrenia patients with high bilirubin level have aggravated psychiatric symptoms. As compared with other psychiatric patients and general population, schizophrenia patients usually have relatively higher bilirubin level; high bilirubin level is associated with acute psychotic states, positive symptoms, and poor prognosis in patients with schizophrenia. This article reviews the relation between bilirubin and schizophrenia and its potential pathophysiological mechanism in order to provide a new direction for the study of schizophrenia pathogenesis and auxiliary diagnosis.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis, which elicits psychological problems in different population This study is to investigate the impact of COVID-19 on mental health in the front-line staff. METHODS: Patient Health Questionnare-9 (PHQ-9), Self-Rating Anxiety Scale (SAS), and Fatigue Self-assessment Scale (FSAS) were used to assess the depression, anxiety, and fatigue in front-line staff. RESULTS: The detection rates of depression, anxiety, and fatigue were 49.1%, 21.8%, and 76.0% among the front-line staff. The rates of depression, anxiety, and fatigue in community workers were higher than those in medical workers and other occupational staff (<0.01). The PHQ-9 of front-line staffs was negatively correlated with age, family income, family members' support, satisfaction of service objects, and sleep quality (all <0.01), while positively correlated with education level, fatigue, fear of pneumonia, and the duration of daily attention to the COVID-19 (all <0.01). SAS was negatively correlated with age, family income, family support, satisfaction of objects service, and sleep quality (all <0.01), while positively correlated with gender, fatigue, fear of pneumonia, and duration of daily attention to the COVID-19 (all <0.01). CONCLUSIONS The front-line workers should manage work and rest time reasonably to adjust their negative mood and fatigue. The government and the society should pay more attention to the psychological state of the front-line staff, particularly for the staff working in the community or villages and towns in preventing the COVID-19 pandemic. Thus, front-line staff can be obtained mental intervention or be taken a rest from the high-intensive work.
Anxiety ; diagnosis ; Betacoronavirus ; Coronavirus Infections ; prevention & control ; psychology ; Depression ; diagnosis ; Fatigue ; diagnosis ; Health Personnel ; psychology ; Humans ; Mental Health ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control ; psychology

Objective To study the relationship of the tibial plateau subchondral trabecular bone (STB) microstructure and the cartilage degeneration with the lower limb alignment based on individual trabecula segmentation (ITS) and histology analysis in knee osteoarthritis (OA). Methods Hip-knee-ankle (HKA) angles were measured on the full-length lower extremity films of patients before total knee arthroplasty (TKA). The tibial plateau excised from the TKA were collected for micro-CT scanning and ITS analysis. The cartilage degeneration was evaluated by histology. The relationship between the HKA angle and the changes in microstructural parameters of STB and cartilage degeneration were analyzed. ResultsThe plate, rod and axial bone trabecular volume fraction (BV/TV, pBV/TV, pBV/TV), ratio of trabecular plate versus rod (P/R), plate trabecular number density (pTb.N), plate trabecular thickness (pTb.Th), trabecular plate surface area (pTb.S), trabecular rod length (rTb.L), and plate-plate and plate-rod junction density (P-P Junc.D, P-R Junc.D) of the subchondral bone of the tibial plateau were significantly related to the cartilage degeneration OARSI score and the HKA angle. The greater the deviation of the lower limb alignment, the greater the number of subchondral trabeculae, the thicker the trabeculae, the greater the bone mass, the stronger the connectivity, especially the plate trabeculae on the affected side of tibial plateau, and the higher the OARSI score of cartilage degeneration. Conclusions Abnormal lower limb alignment may cause abnormal microstructure of the plate and rod STB of the tibial plateau by changing the stress distribution of the knee, especially the significant increase and thickening of the plate trabecular and axial trabecular bone, which may be an important risk factor that further aggravates the degeneration of articular cartilage and the progress of OA. Therefore, lower limb alignment correction with surgical intervention and improving STB with bone metabolism agents may efficiently contribute to preventing cartilage damage and mitigate OA progression.

Objective:To investigate the reproducibility of inflow-based vascular-space-occupancy (iVASO)-MRI in quantifying skeletal muscle perfusion and its potential clinical value in patients with dermatomyositis (DM).Methods:Totally 15 consecutive patients with DM and 15 healthy volunteers were enrolled in this prospective study from December 2018 to April 2019 at Nanfang Hospital, Southern Medical University. All subjects underwent T 1WI, short-tau inversion recovery (STIR) T 2WI, and iVASO-MRI of thigh on a 3.0 T MR scanner. According to findings on T 1WI and STIR T 2WI, the muscles were divided into normal, unaffected, edematous and atrophic or fat-infiltrated groups. Maximum arteriolar muscular blood volume (MBVa_max) and mean MBVa (MBVa_mean) of these 4 groups of muscles were obtained by 2 radiologists independently. In order to evaluate the reproducibility of iVASO, the repeated scan was performed 3 days later in 17 subjects (12 healthy volunteers and 5 DM patients), and the MBVa values were measured to calculate the intraclass correlation coefficients (ICC). The MBVa_max and MBVa_mean among the 4 groups were compared by using Kruskal-Wallis H test and the differences of each 2 groups was compare by using Mann-Whitney U test. Results:The ICC between the 2 observers was 0.95 and 0.96 for MBVa_max and MBVa_mean, respectively. The ICC between repeated tests was 0.87 and 0.89 for MBVa_max and MBVa_mean, respectively.There was significant difference among normal muscles, unaffected muscles, edematous muscles and atrophic or fat-infiltrated muscles ( P<0.001). Post hoc comparisons of MBVa_max and MBVa_mean showed that compared to normal muscles, unaffected muscles, edematous muscles and atrophic or fat-infiltrated muscles had a significant decrease of MBVa ( P<0.05). Unaffected muscles and edematous muscles showed no significant difference in terms of MBVa_max and MBVa_mean (both P=0.99), which were significantly higher than those of atrophic or fat-infiltrated muscles ( P<0.05). Conclusions:iVASO-MRIcan reliably quantify the MBVa of thigh muscular arteriolar, and it is potentially valuable in the diagnosis of DM.

PURPOSE: As midwives witness and attend the whole process of childbirth, they have a better understanding of which factors may cause traumatic childbirth. However, because most of the studies paid their attention on mothers, little is known about psychological birth trauma from the perspective of midwives. This study aims to gain a full understanding of which factors may contribute to psychological traumatic childbirth from the perspective of midwives.METHODS: A qualitative research was conducted using in-depth interviews, which involved fourteen midwives from the maternal ward of a tertiary hospital. The interviews were recorded and transcribed, and then, Colaizzi's method was used to analyze the contents of the interviews.RESULTS: We proposed four themes and eight subthemes on the influencing factors of psychological traumatic childbirth from the perspective of midwives: low perceived social support (lack of support from family and lack of support from medical staff), hard times (protracted labor in the first stage and futile efforts during the second stage), poor birth outcomes (poor birth outcomes of the mother and poor birth outcomes of the baby), and excruciating pain (unbearable pain of uterine contraction and labor pain was incongruent with the mother's expectations).CONCLUSION: Medical staff should pay attention to psychological traumatic childbirth and its effects, and emphasis on the screening and assessment of birthing women with negative feelings so that their psychological traumatic childbirth can be prevented and decreased.
Female ; Humans ; Labor Pain ; Mass Screening ; Medical Staff ; Methods ; Midwifery ; Mothers ; Natural Childbirth ; Parturition ; Pregnancy ; Psychological Trauma ; Qualitative Research ; Tertiary Care Centers ; Uterine Contraction

OBJECTIVETo explore the value of detecting podocalyxin (PCX) level in urinary extracellular vesicles for the diagnosis of diabetic nephropathy.

METHODSThis study was conducted among 57 diabetic patients admitted during the period from March to September, 2017, including 34 with uncomplicated diabetics and 23 with diabetic nephropathy; 21 patients with other types of nephropathy and 11 healthy individuals were also included to serve as the controls. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were used to verify the separation of urinary extracellular vesicles. The molecular markers of extracellular vesicles (TSG101 and podocalyxin [PCX]) were detected using Western blotting. PCX levels in extracellular vesicles were also detected using ELISA.

RESULTSTEM reveal the presence of numerous extracellular vesicles in the urine with intact morphology and different sizes, and most of them were below 300 nm in diameter as shown by NTA. TSG101 expression was detected in the samples from all the 4 groups. Positive expression of PCX was detected in the samples from patients with diabetic nephropathy but not in the other groups. In patients with diabetic nephropathy, the mean PCX levels (3.27±2.30 ng/μmol)was significantly higher than those in the healthy control group (1.22±0.36 ng/μmol), uncomplicated diabetes group (2.22±1.29 ng/μmol) and nephropathy group (1.24±0.45 ng/μmol).

CONCLUSIONSPCX level in urinary extracellular vesicles is significantly increased in patients with diabetic nephropathy, suggesting the value of PCX as a potential marker for clinical diagnosis of diabetic nephropathy.