This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L^-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
Animals ; Mice ; RANK Ligand/genetics* ; RAW 264.7 Cells ; Osteoclasts/metabolism* ; Benzopyrans/isolation & purification* ; Osteogenesis/drug effects* ; Macrophages/metabolism* ; Molecular Structure ; Pigments, Biological/isolation & purification* ; Ascomycota/chemistry* ; NF-kappa B/genetics* ; Cell Differentiation/drug effects*

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Humans ; Blood Pressure/physiology* ; Cohort Studies ; Patient Discharge ; Ischemic Stroke ; Stroke ; Brain Ischemia ; Diabetes Mellitus ; Hypertension

Objective:To investigate the comprehensive ability and influencing factors of clinical medicine graduates from a medical college in Xi'an, and provide a scientific basis for improving the training model and comprehensive ability of clinical medicine students.Methods:Based on the Chinese Undergraduate Medical Education Standard-Clinical Medicine Specialty (2016 Edition), we conducted a self-designed questionnaire, the Clinical Medicine Graduate Comprehensive Ability Evaluation Questionnaire, containing 62 items in 4 dimensions, selected the clinical medicine graduates as the research objects by random sampling method, used SPSS 22.0 to make data analysis, and performed multiple linear regression to analyze its influencing factors.Results:Clinical medicine graduates had the highest score in the field of clinical competence (3.05±0.84), followed by the field of professionalism (2.48±0.81), and the lowest score was in the field of science and academics (1.89±0.68). The top three scores of each factor were clinical practice ability (3.39±0.76), theoretical knowledge mastery (3.55±0.48) and medical knowledge mastery (2.98±0.81). The three factors with the lowest scores were literature search ability (1.31±0.64), global health issues (1.49±0.82) and self-improvement willingness and ability (1.81±0.73). Using the multiple stepwise regression method to analyze the influencing factors of comprehensive ability, the optimal equation was obtained: Y=8.412+0.063 X6+0.190 X8+0.266 X10+0.031 X11+0.187 X12 ( X6, working level; X8, academic performance ranking; X10, practical teaching satisfaction; X11, mode of teaching satisfaction; X12, Re-education satisfaction after graduation). Among them, the higher the practical teaching satisfaction, the satisfaction of re-education and the satisfaction of teaching mode after graduation, the higher the student's performance ranking, and the higher the comprehensive ability score of clinical graduates. Graduates whose employment level was in a general hospitals had higher comprehensive ability scores than those of grassroots hospitals such as community/township hospitals. Conclusions:In the process of training clinical medicine students, we should improve the quality of practical teaching and the teaching model, increase the training of science and academic fields, increase the investment in re-education of primary medical institutions, and raise the satisfaction of graduates in education, so as to improve the clinical medicine profession comprehensive ability of graduates.

Objective:To determine the dose-effect relationship of nalbuphine preventing injection pain of medium plus long chain triglyceride propofol in pediatric patients undergoing gastroenteroscopy.Methods:Pediatric patients, aged 3-8 yr, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, scheduled for elective gastroenteroscopy, were enrolled in the study.The doses of nalbuphine were determined by up-down sequential allocation, nalbuphine 0.2 mg/kg was injected intravenously in the first child, and 5 min later medium plus long chain triglyceride propofol 2.5 mg/kg was given intravenously.Ambesh 4-point method was used to evaluate the injection pain of propofol.When the prevention of injection pain was ineffective, the dose of nalbuphine was increased in the next patient, otherwise the dose was reduced, and the difference between the two successive doses was 0.01 mg/kg.This process was repeated until the 7th turning point occurred.The ED 50 and ED 95 of nalbuphine and 95% confidence interval (CI) preventing injection pain of propofol were calculated by Probit regression. Results:The ED 50 and ED 95 (95% CI) of nalbuphine preventing medium plus long chain triglyceride propofol injection pain were 1.57 (1.50-1.62) and 1.71 (1.64-2.05) mg/kg, respectively. Conclusion:The ED 50 and ED 95 of nalbuphine preventing injection pain of medium plus long chain triglyceride propofol are 1.57 and 1.71 mg/kg, respectively, in pediatric patients undergoing gastroenteroscopy.

Objective:To evaluate the efficacy of auricular acupoint pressure therapy combined with intranasal dexmedetomidine for transthoracic echocardiography in pediatric patients.Methods:A total of 117 pediatric patients with congenital heart disease, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, aged 3-36 months, weighing 5-20 kg, scheduled for elective transthoracic echocardiography under outpatient sedation, were selected.Transthoracic echocardiography was performed under sedation using intranasally administered dexmedetomidine or using auricular acupoint pressure therapy combined with intranasal dexmedetomidine.The interval between the two sedation methods was at least 1 week.Intranasal dexmedetomidine: Dexmedetomidine 3 μg/kg was administered to both nostrils via a nebulizer, with 1/2 dose in each nostril.Intranasal dexmedetomidine combined with auricular acupoint pressure: auricular acupressure with Wang Bu Liu Xing (semen vaccariae) seeds was used at the auricular acupoints.After each acupoint was rubbed for about 1 min, dexmedetomidine 3 μg/kg was administered to both nostrils via a nebulizer, with 1/2 dose in each nostril.After the examination, auricular acupoint pressure therapy was continued at home, and pressing-rubbing at the acupoints was manipulated for 3 times daily, one of which was performed at 30 min before going to bed, for 3 consecutive days.When the University of Michigan Sedation Scale score≥2 and body movement score ≥2 within 30 min after giving dexmedetomidine, sedation was considered to be successful.The onset time of sedation, examination time, waiting time, recovery time and the success of sedation were recorded.The incidence of adverse reactions such as bradycardia, hypotension, hypertension, hypoxemia, nausea and vomiting, respiratory depression, restlessness, hyperactivity, action imbalances and allergic reaction were recorded within 24 h after administration of dexmedetomidine.Time to recovery and improvement of sleep quality at night were recorded.Results:Compared with intranasal dexmedetomidine, the successful rate of sedation and incidence of improvement of sleep quality at night were significantly increased ( P<0.05), and no significant change was found in adverse reactions using intranasal dexmedetomidine combined with auricular acupoint pressure ( P>0.05). Conclusion:Intranasal dexmedetomidine combined with auricular acupoint pressure therapy can increase the successful rate of sedation and improve the sleep quality at night in pediatric patients undergoing transthoracic echocardiography when compared to intranasal dexmedetomidine.

OBJECTIVE: To evaluate the effect of general anesthesia on postoperative melatonin secretion in 4-to 6-year-old children with snoring. METHODS: Twenty children with snoring aged 4-6 years of either gender (ASA grade Ⅰ and Ⅱ) were selected for adenoidectomy.Before, during and 3 days after the operation, salivary melatonin levels of the children were measured at 11 selected time points (T1-T11).The illumination intensity and body temperature of the children were recorded at each time point of measurement.The sleep time of the children in 3 days after the operation was recorded, and postoperative pain scores (FLACC) and Riker and Rehabilitation Quality Rating Scale-15(QoR-15) scores were assessed.Sleep Apnea Life Quality Evaluation Questionnaire (OSA-18) was used to evaluate postoperative recovery of the children at 28 days after the operation.The incidence of major adverse events of the children during hospitalization was recorded. RESULTS: No significant difference was found in baseline salivary melatonin level among the 20 children before the operation.Salivary melatonin level at 7 am after the operation (T8) was significantly lowered as compared with that before the surgery (T4)( CONCLUSIONS In preschool children with snoring, general anesthesia affects but does not inhibit melatonin secretion on the first night after surgery, and minor surgeries under general anesthesia in the morning do not cause significant changes in melatonin secretion to cause disturbance of the circadian rhythm in these children.
Anesthesia, General/adverse effects* ; Bodily Secretions ; Child ; Child, Preschool ; Circadian Rhythm ; Humans ; Melatonin ; Snoring

Objective:To study the early effects of intact-umbilical cord milking (I-UCM) and cut-umbilical cord milking (C-UCM) for the prevention of anemia of prematurity in preterm infants.Method:From January 2019 to October 2019, C-section delivered infants with gestational age <34 weeks were randomly assigned into I-UCM group and C-UCM group. Hematological parameters at different timepoints after birth, iron status, incidence of anemia within 7 d after birth, blood transfusions, transcutaneous bilirubin levels and the total duration of phototherapy were collected and analyzed.Result:A total of 60 cases were enrolled, including 30 in I-UCM group and 30 in C-UCM group. I-UCM group had significant higher levels of hemoglobin (Hb), hematocrit (Hct) and serum iron on admission ( P<0.05). Comparing with C-UCM group, Hb and Hct were significantly higher in I-UCM group at 7 d and 14 d after birth ( P<0.05). Lower prevalence of anemia within 1 week [3.3% (1/30) vs. 33.3% (10/30), P<0.05] and less blood transfusions during hospitalization [13.3% (4/30) vs. 56.7% (17/30)] were noted in I-UCM group. No statistically significant differences existed between the two groups in phototherapy duration and the peak bilirubin levels ( P>0.05). Conclusion:I-UCM can provide more placental transfusion at birth to increase Hb levels and iron storage to prevent and reduce anemia in preterm infants.