Objective To study the factors influencing the blood concentration of caspofungin(CPFG),construct a prediction model,and validate the predictive effect of the model,so as to provide reference for the individualised dosing of patients with fungal infections in haematology.Methods Seventy-five patients admitted to the Department of Haematology,General Hospital of Tianjin Medical University,who were treated with CPFG for antifungal therapy during the period of March 2021 to June 2022 were selected as the study subjects,and CPFG blood concentration monitoring was carried out to explore the influencing factors of CPFG blood concentration and to construct a prediction model accordingly.Hosmer-Lemeshow(H-L)was used to test the goodness-of-fit of the model,and another 30 patients were selected as the verification group,and the predictive effect of the model was verified by the receiver's operating characteristics(ROC)curve.Results The mean blood concentrations of the patients at 0.5,9 and 24 h were(12.54±4.38),(6.80±2.76),(4.13±2.16)μg·mL-1,and the mean AUC0-24h were(152.05±57.60)μg·mL-1·h.AUC0-24h was lower than the reference value(98 μg·mL-1·h)in two patients.The results of correlation analysis showed that gender showed a correlation with 0.5 h blood concentration(P＜0.05),and there was no correlation with the rest of the two time points blood concentration and AUC0-24h(P＞0.05).Body weight and albumin(Alb)concentration showed correlation with 0.5,9,24 h blood drug concentration and AUC0-24 h(P＜0.05),and the rest of the indicators showed no correlation with blood drug concentration and AUC0_24h at each time point(P＞0.05).The results of multifactorial analysis showed that the factors influencing the patients'0.5 h blood concentration were gender,Alb concentration and body weight,and the factors influencing the 9 and 24 h blood concentration and AUC0-24h were Alb concentration and body weight(P＜0.05).Correlation analysis showed that the daily dose was positively correlated with the plasma concentration of CPFG at 0.5,9 and 24 h and AUC0-24h(P＜0.05).The results of multivariate analysis showed that the daily dose was also one of the influencing factors of the plasma concentration of CPFG(P＜0.05).ROC curve shows that the model has good prediction ability.Conclusion Body weight and Alb are significantly associated with CPFG blood concentrations and area under the drug-time curve,which can be used as a basis for preventive risk avoidance.

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1β(IL-1β) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1β showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.
Rats ; Animals ; Chondrocytes ; Osteoarthritis, Knee/pathology* ; RNA, Circular/pharmacology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MicroRNAs/metabolism* ; Apoptosis ; Autophagy/genetics* ; Collagen/metabolism*

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×10⁹/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×10⁹/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.
Male ; Female ; Humans ; Child ; Retrospective Studies ; RUNX1 Translocation Partner 1 Protein/genetics* ; Core Binding Factor Alpha 2 Subunit/therapeutic use* ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Cytarabine/therapeutic use* ; Oncogene Proteins, Fusion/genetics* ; Chromosome Aberrations

The purpose of this study was to explore the clinical efficacy and safety of Gynostemma pentaphyllum (G. pentaphyllum) in the treatment of hyperlipidemia, and to provide systematic evaluation basis for clinical application. CNKI, Wanfang Data, VIP, Web of science, PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) about G. pentaphyllum in the treatment of hyperlipidemia. Review Manager 5.4 were used for statistical analysis. Through reading topics, abstracts, and full texts, 27 papers with 2311 cases involved that met the inclusion and exclusion criteria were finally included for the analysis. In terms of curative effect, the effect of G. pentaphyllum alone in increasing high density lipoprotein (HDL) index was better than that of conventional treatment, and the effect of reducing total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) was similar to that of conventional treatment. There was a synergistic effect between G. pentaphyllum and conventional drugs, and the combination of G. pentaphyllum and conventional drugs was superior to conventional treatment in reducing TG and increasing HDL. G. pentaphyllum can also decrease the levels of serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in the treatment of hyperlipidemia, indicating a certain protective function of the liver. In terms of safety, there were fewer cases of adverse reactions in the G. pentaphyllum treatment group, and the adverse reaction events reported in the literature was mild. According to the results of meta-analysis, G. pentaphyllum was effective in the treatment of hyperlipidemia, and it has the potential to be combined with traditional drugs, has a certain liver protection function, and was superior to traditional drugs in the treatment of hyperlipidemia.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Genetic Diseases, Inborn ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology*

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.

The "student-centered" flipped classroom teaching model can improve students' academic achievement, improve cognition, and cultivate innovation ability. However, it has obvious deficiencies in the integrity and systematization of knowledge as well as education. The traditional teaching concept based on " teacher-centered" has the unique advantages of systematization of knowledge learning and education. Therefore, we integrated the merits of these two different teaching models and introduced the semi-flipped classroom teaching model into the Biochemistry teaching of 2020 stomatology, pharmacy and preventive medicine majors in Cheeloo Medical College, Shandong University, compared with the traditional teaching of 2019 same majors. The data on the improvement of students ' academic achievement and self-cognition were analyzed. The results showed that the students' achievements of the semi-flipped classroom teaching model were better than those of the traditional teaching (P<0. 01). The students' self-cognitions were significantly improved after the implementation of semi-flipped classroom teaching (P<0. 01 or P<0. 05). This study provides a reference for the related teaching and research work in medical colleges.

Objective:To investigate the protective effect of quercetin （Qu） on articular cartilage of knee osteoarthritis and its mechanism by inhibiting p38 mitogen activated protein kinase （MAPK） signaling pathway. Method:Through the network pharmacology technology，we scientifically predicted and analyzed the target factors and signal pathways of Qu in the protection of articular cartilage in patients with osteoarthritis. We selected a prediction pathway closely related to osteoarthritis and validated it by cell experiment in vitro. The best intervention concentration of the drug was selected by cell counting kit-8 （CCK-8） method. The osteoarthritis and its closely related inflammatory factors interleukin（IL）-1β and tumor necrosis factor（TNF）-α were detected by enzyme linked immunosorbent assay（ELISA）. The expression of related mRNA and protein in p38 signal pathway after Qu intervention were detected by quantitative real time polymerase chain reaction（Real-time PCR） and Western blot. Result:It was predicted that MAPK signal pathway was closely related to osteoarthritis by network pharmacology，and p38 MAPK pathway，which was most closely related to osteoarthritis，was selected for study. The results showed that 100 μmol·L^-1 Qu had the most obvious effect in decreasing the expression of related inflammatory factors，inhibited the expression of p38，phosphorylated（p）-p38，matrix metalloproteinase-13（MMP-13），A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-4（ADAMTS-4） in the pathway，and promoted the expression of CollagenⅡ. Conclusion:Qu could decrease the expression of cartilage inflammatory factors in the prevention and treatment of osteoarthritis，and the effect can be well developed by intervening and inhibiting p38 MAPK pathway related factor expression level. All the results show that Qu can decrease osteoarthritis inflammatory factors and protect articular cartilage in patients with osteoarthritis.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in