Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

ObjectiveGlutathione (γ-glutamyl-L-cysteinylglycine, GSH) is the most abundant non-protein compound containing sulfhydryl (―SH) groups in cells. It serves as a source of reducing equivalents, effectively neutralizing harmful reactive substances, and playing a crucial role in maintaining cellular redox balance. Therefore, sensitive detection and accurate measurement of GSH levels in tissues are of great importance. In this work, we presents a novel method for GSH detection utilizing electron paramagnetic resonance (EPR) spectroscopy. MethodsInitially, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate acid)) solution was mixed with K₂S₂O₈ solution and reacted in the dark for 12 to 16 h to prepare ABTS·⁺ solution, which was then quantified using UV-Vis spectroscopy. Subsequently, the concentration of glutathione (GSH) was determined based on the changes in the EPR signal of ABTS·⁺. On this basis, the optimal reaction time and temperature were explored to establish a standard equation correlating the EPR signal intensity of ABTS·⁺ with GSH concentration. Finally, the derived standard curve was employed to quantitatively analyze the GSH concentration in whole blood from C57BL/6J mice, and the results were compared with those reported in the literature to verify the accuracy of the method. ResultsThe experimental results demonstrate that this method has a linear detection range from50 nmol/L to 15 μmol/L for GSH, spanning two orders of magnitude, with a limit of detection (LOD) at0.50 nmol/L. The measured GSH content in mouse whole blood is (10 660±706) nmol/g Hb, which agrees with the value of (11 200±237) nmol/g Hb as previously reported. Furthermore, a similar method was developed for detection of glutathione disulfide (GSSG) at higher reaction temperature. ConclusionThis article presents a novel assay for the rapid detection of GSH using the intensity of EPR signal from ABTS·⁺ as indicator. This method demonstrates enhanced detection sensitivity and a broader linear range compared to conventional colorimetric methods. Furthermore, we have extended the application of this method to detect GSH content in blood samples efficiently and accurately, offering valuable information for assessing tissue redox balance, thus holding significant potentials.

Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder(CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD.Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA,FGB,and FGG genes,and sequencing was performed to analyze mutation characteristics.Results Among the 16 children,there were 9 boys(56%)and 7 girls(44%),with a median age of 4 years at the time of attending the hospital.Among these children,9(56%)attended the hospital due to bleeding events,and 7(44%)were diagnosed based on preoperative examination.The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events(P<0.05).Genetic testing was conducted on 12 children and revealed a total of 12 mutations,among which there were 4 novel mutations,i.e.,c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene.There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene,with relatively severe bleeding symptoms.There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes,and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous,and the severity of bleeding is associated with the level of fibrinogen activity,but there is a weak association between clinical phenotype and genotype.

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

China ; Humans ; Otolaryngology

OBJECTIVE: To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties. METHODS: Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized. RESULTS: SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets. CONCLUSION The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.
Drug Liberation ; Excipients ; Printing, Three-Dimensional ; Reproducibility of Results ; Tablets

Objective: To observe the blood perfusion volume variation pattern in the body surface microcirculation at the Yuan-Primary and the Xi-Cleft points during the menstrual cycle in female college students with moderate constitution under normal physiological state of the uterus; to explore the specific laws of the body surface microcirculation at the Yuan-Primary and Xi-Cleft points in response to the uterine qi and blood changes under normal physiological conditions, and to provide the experimental basis for the specificity of acupoints reflecting the uterine function. Methods: Forty-three healthy and moderate constitution female college students with regular menstrual cycles, without dysmenorrhea and not yet giving birth were recruited. Bilateral Yuan-Primary points [Taichong (LR 3), Taibai (SP 3) and Taixi (KI 3)] and Xi-Cleft points [Zhongdu (LR 6), Diji (SP 8) and Shuiquan (KI 5)], belonging to the three yin meridians of foot and adjacent to the spinal cord segment of the uterus, were selected as the detection acupoints; the crossing point of the three yin meridians of foot [Sanyinjiao (SP 6)], the uterus-related meridian acupoint [Xuehai (SP 10)], the uterus-non-related meridian acupoint [Xuanzhong (GB 39)], and the non-meridian non-acupoint point were selected as the control points. The laser speckle blood flow imaging technique was used to monitor the blood perfusion volume in skin microcirculation at the above points at the menstrual, follicular, ovulatory, and luteal phases of the subjects. Results: The blood perfusion volume in the body surface microcirculation at the right Zhongdu (LR 6) at the ovulatory phase was higher than that at the menstrual, follicular and luteal phases (all P<0.05); there was no significant difference in the microcirculation blood perfusion volume at the other points among different phases (all P>0.05). Conclusion: The blood perfusion volume in the body surface microcirculation at Zhongdu (LR 6), the Xi-Cleft point of the Liver Meridian, shows a specific response to qi and blood changes in the uterus of women with moderate constitution.

OBJECTIVE: To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥100×109/L; n=263) and thrombocytopenia group (platelet count <100×10/L; n=629). The thrombocytopenia group was further divided into (50- <100)×10/L (n=243), (20- <50)×10/L (n=263), and <20×10/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. RESULTS: Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P<0.05), as well as a significantly higher 10-year EFS rate (P<0.05). There was no significant difference in 10-year OS between the two groups (P>0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P<0.05), and there was still no significant difference in 10-year OS between the two groups (P>0.05). The <20×10/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- <100)×10/L subgroup, and the (20- <50)×10/L subgroup (P<0.05). After the children with MLL gene rearrangement were excluded, the <20×10/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50-<100)×10/L subgroup, and the (20- <50)×10/L subgroup (P<0.05). CONCLUSIONS ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of <20×10/L have the worst prognosis.
Child ; Disease-Free Survival ; Humans ; Immunophenotyping ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence

Objective To document the impact of conversion to mycophenolate mofetil (MMF)at different time points after transplantation on the renal function of renal function.Methods A longterm,multicenter,non-interventional and observational study was done.Two cohorts were included:One was Switch cohort (340 cases) including renal allograft recipients who switched to MMF at least 6 months after renal transplantation and followed up for 4 years after switch; The other was Stay cohort (123 cases),including renal allograft recipients who received MMF treatment after transplantation and followed up for 4 years after enrollment.Results GFR values of patients in Switch cohort was significantly increased after switch,and the change in GFR slope was 3.1 mL· min-1 · year-1 (P＜0.01).GFR values of patients in Stay cohort kept steady before and after enrollment,and the change in GFR slope was 0.44 mL·min-1 ·year-1 (P＞0.05).Statistically significant difference in the onset time of GFR decline (defined as 20％ decline from the baseline) was observed among subgroups within Switch cohort (P＜0.01),but there was no significant difference among subgroups within Stay cohort (P＞0.05).Stay cohort was 12％ higher than in Switch cohort every year.Conclusion Conversion to MMF ＞6 months or even many years after transplantation can obviously improve the renal function of recipients.The earlier conversion can benefit improvement of the renal function.

OBJECTIVETo evaluate retrospectively the results of arthroscopic Bankart repair using suture anchors for recurrent anterior shoulder dislocation with a minimum 1-year follow-up and to assess risk factors for recurrence.

METHODSFrom March 2002 to March 2010, 259 patients with recurrent anterior shoulder dislocation underwent arthroscopic Bankart repair with suture anchors. And 188 patients (50 athletes, 138 nonathletes) were available for follow-up. The mean age at the time of surgery was 25.3 years (range, 13 - 58 years). The mean follow-up was 38.6 months (range, 12 - 110 months). All of the 188 patients were evaluated preoperatively and postoperatively with the American Shoulder and Elbow Society (ASES) shoulder score and Rowe score system. The rate of recurrent instability, range of motion, and risk factors for postoperative recurrence were evaluated. The ASES score was 72.6 preoperatively, and Rowe score was 33.4.

RESULTSThe ASES scores improved significantly to 91.9 postoperatively (P < 0.001). The Rowe scores improved to 81.9 postoperatively (P < 0.001). And 152 patients were greatly satisfied with the results, 16 satisfied and 20 unsatisfied. The satisfactory rate was 89.4%. 24 patients (12.8%) suffered a recurrence after surgery, 14 athletes and 10 nonathletes. The recurrence rates were 28.0% in the athlete group and 7.2% in the nonathlete group. On average there was no significant loss of external rotation postoperatively (average, 75.2° preoperatively and 67.2° postoperatively). Patients under age 20, and athlete patients were associated with recurrence (P < 0.05). Other factors including length of time until surgery, type of anchors, number of anchors, presence of bony Bankart lesion, presence of a superior labrum, anterior and posterior tear, presence of posterior or inferior labrum lesion, presence of rotator cuff tear, ligamentous laxity and rotator interval closure did not influence the recurrence rate (P > 0.05).

CONCLUSIONSArthroscopic Bankart repair is a good option for the treatment of recurrent anterior shoulder dislocation. Identification of risk factors for recurrence allows for consideration of open stabilization. In the series, patients under age 20 and athlete patients are the most important risk factors for recurrence.

Adolescent ; Adult ; Arthroscopy ; Athletes ; Female ; Humans ; Joint Instability ; Male ; Middle Aged ; Range of Motion, Articular ; Recurrence ; Retrospective Studies ; Risk Factors ; Shoulder Dislocation ; pathology ; surgery ; Suture Anchors ; Treatment Outcome ; Young Adult