MACHINE LEARNING FOR PREDICTING HEMODYNAMIC DETERIORATION OF PATIENTS WITH INTERMEDIATE-RISK PULMONARY EMBOLISM IN INTENSIVE CARE UNIT.

ABSTRACT: Background: Intermediate-risk pulmonary embolism (PE) patients in the intensive care unit (ICU) are at a higher risk of hemodynamic deterioration than those in the general ward. This study aimed to construct a machine learning (ML) model to accurately identify the tendency for hemodynamic deterioration in the ICU patients with intermediate-risk PE. Method: A total of 704 intermediate-risk PE patients from the MIMIC-IV database were retrospectively collected. The primary outcome was defined as hemodynamic deterioration occurring within 30 days after admission to ICU. Four ML algorithms were used to construct models on the basis of all variables from MIMIC IV database with missing values less than 20%. The extreme gradient boosting (XGBoost) model was further simplified for clinical application. The performance of the ML models was evaluated by using the receiver operating characteristic curve, calibration plots, and decision curve analysis. Predictive performance of simplified XGBoost was compared with the simplified Pulmonary Embolism Severity Index score. SHapley Additive explanation (SHAP) was performed on a simplified XGBoost model to calculate the contribution and impact of each feature on the predicted outcome and presents it visually. Results: Among the 704 intermediate-risk PE patients included in this study, 120 patients experienced hemodynamic deterioration within 30 days after admission to the ICU. Simplified XGBoost model demonstrated the best predictive performance with an area under the curve of 0.866 (95% confidence interval, 0.800-0.925), and after recalibrated by isotonic regression, the area under the curve improved to 0.885 (95% confidence interval, 0.822-0.935). Based on the simplified XGBoost model, a web app was developed to identify the tendency for hemodynamic deterioration in ICU patients with intermediate-risk PE. Conclusion: A simplified XGBoost model can accurately predict the occurrence of hemodynamic deterioration for intermediate-risk PE patients in the ICU, assisting clinical workers in providing more personalized management for PE patients in the ICU.

BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis.

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

Influences of Cu Doping on the Microstructure, Optical and Resistance Switching Properties of Zinc OxideThin Films.

Copper-doped zinc oxide films (Zn1-xCuxO) (x = 0, 2%, 4%, 6%) were fabricated on conductive substrates using the sol-gel process. The crystal structure, optical and resistive switching properties of Zn1-xCuxO films are studied and discussed. RRAM is made using Zn1-xCuxO as the resistive layer. The results show that the (002) peak intensity and grain size of Zn1-xCuxOfilms increase from 0 to 6%. In addition, PL spectroscopy shows that the oxygen vacancy defect density of Zn1-xCuxO films also increases with the increase in Cu. The improved resistive switching performance of the RRAM device can be attributed to the formation of conductive filaments and the destruction of more oxygen vacancies in the Zn1-xCuxO film. Consequently, the RRAM device exhibits a higher low resistance state to high resistance state ratio and an HRS state of higher resistance value.

Activation Energy and Bipolar Switching Properties for the Co-Sputtering of ITOX:SiO2 Thin Films on Resistive Random Access Memory Devices.

Activation energy, bipolar resistance switching behavior, and the electrical conduction transport properties of ITOX:SiO2 thin film resistive random access memory (RRAM) devices were observed and discussed. The ITOX:SiO2 thin films were prepared using a co-sputtering deposition method on the TiN/Si substrate. For the RRAM device structure fabrication, an Al/ITOX:SiO2/TiN/Si structure was prepared by using aluminum for the top electrode and a TiN material for the bottom electrode. In addition, grain growth, defect reduction, and RRAM device performance of the ITOX:SiO2 thin film for the various oxygen gas flow conditions were observed and described. Based on the I-V curve measurements of the RRAM devices, the turn on-off ratio and the bipolar resistance switching properties of the Al/ITOX:SiO2/TiN/Si RRAM devices in the set and reset states were also obtained. At low operating voltages and high resistance values, the conductance mechanism exhibits hopping conduction mechanisms for set states. Moreover, at high operating voltages, the conductance mechanism behaves as an ohmic conduction current mechanism. Finally, the Al/ITOX:SiO2/TiN/Si RRAM devices demonstrated memory window properties, bipolar resistance switching behavior, and nonvolatile characteristics for next-generation nonvolatile memory applications.

ENO1 promotes immunosuppression and tumor growth in pancreatic cancer

Background Pancreatic adenocarcinoma (PAAD) is a highly aggressive and malignant cancer type with the highest mortality rate of all major cancers. However, the molecular and tumor immune escape mechanism underlying pancreatic cancer remains largely unclear. α-enolase (ENO1) is a glycolytic enzyme reported to overexpress in a variety of cancer types. This study was undertaken to investigate the functional role and therapeutic potential of ENO1 in pancreatic cancer. Methods We examined the expression levels of ENO1 across a broad spectrum of cancer types from the TCGA database. ENO1-knockout (ENO1-KO) through CRISPR/CAS9 technology in a mouse pancreatic cancer cell line (PAN02) was used to analyze the role of ENO1 on proliferation and colony formation. Flow cytometry and RT-PCR were also applied to analyze T lymphocytes and relevant cytokines. Results In the present study, we identified that ENO1 promoted pancreatic cancer cell proliferation. Our bioinformatics data indicated that ENO1 was significantly overexpressed in pancreatic cancer cell lines and tissues. Survival analyses revealed that ENO1 overexpression implicated poor survival of PAAD patients. Knockout of ENO1 expression repressed the ability of proliferation and colony formation in PAN02. In addition, ENO1-KO significantly decreased tumor growth in mouse models. Further flow cytometry and RT-PCR analysis revealed that ENO1-KO modulates the tumor microenvironment (TME), especially in suppressed Treg cells and inducing anti-tumor cytokine responses. Conclusions Taken together, our data showed that ENO1 was an oncogenic biomarker and might serve as a promising target for immunotherapy of pancreatic cancer (AU)

Bipolar Switching Properties of the Transparent Indium Tin Oxide Thin Film Resistance Random Access Memories.

In this study, the bipolar switching properties and electrical conduction behaviors of the ITO thin films RRAM devices were investigated. For the transparent RRAM devices structure, indium tin oxide thin films were deposited by using the RF magnetron sputtering method on the ITO/glass substrate. For the ITO/ITOX/ITO/glass (MIM) structure, an indium tin oxide thin film top electrode was prepared to form the transparent RRAM devices. From the experimental results, the 102 On/Off memory ratio and bipolar switching cycling properties for set/reset stable states were found and discussed. All transparent RRAM devices exhibited the obvious memory window and low set voltage for the switching times of 120 cycles. The electrical transport mechanisms were dominated by the ohmic contact and space charge limit conduction (SCLC) models for set and reset states. Finally, the transmittances properties of the transparent ITO/ITOX/ITO RRAM devices for the different oxygen growth procedures were about 90% according to the UV-Vis spectrophotometer for the visible wavelength range.

First Order Rate Law Analysis for Reset State in Vanadium Oxide Thin Film Resistive Random Access Memory Devices.

In the reset state, the decay reaction mechanism and bipolar switching properties of vanadium oxide thin film RRAM devices for LRS/HRS are investigated and discussed here. To discover the properties of I-V switching curves, the first order rate law behaviors of the reset state between the resistant variety properties and the reaction time were observed. To verify the decay reaction mechanism in the reset state, vanadium oxide thin films from RRAM devices were measured by different constant voltage sampling and exhibited the same decay reaction rate constant. Finally, the electrical conduction transfer mechanism and metallic filament forming model described by I-V switching properties of the RRAM devices were proven and investigated.

Role of glutathione transferase in nonalcoholic fatty liver disease: An analysis based on gene expression profile / 临床肝胆病杂志

Objective To investigate the role of glutathione transferase in nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet using the RNA-Seq technique in combination with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes. Methods A total of 14 male C57BL/6J mice were divided into control group with 6 mice and model group with 8 mice by random sampling. The mice in the control group were fed with normal diet, and those in the model group were fed with high-fat diet for 7 consecutive weeks to establish a model of NAFLD. Kits were used to measure the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the level of triglyceride (TG), and HE staining and oil red staining were used to observe liver pathology and deposition of lipid droplets. Liver tissue RNA was extracted for RNA-Seq, and genes with a fold change of ≥2.0 and a P value of 0.05). Compared with the control group, the model group had a significantly higher serum level of TG (2.02±0.50 mmol/L vs 1.00±0.29 mmol/L, t =-4.45, P =0.001). HE staining showed diffuse steatosis and ballooning degeneration in the model group, and oil red staining showed that the model group had a significant increase in orange-red lipid droplets in the cytoplasm of hepatocytes and a significantly higher grade of hepatocyte steatosis than the control group (1.88±0.64 vs 1.00±0.00, t =-3.86, P =0.006). RNA-seq results showed a total of 1367 differentially expressed genes between the two groups, among which there were 608 upregulated genes and 759 downregulated genes, and there were 17 differentially expressed GST genes between the two groups. The top 10 GST genes in terms of fold change were validated, and compared with the control group, the model group had downregulated expression of GSTa2, GSTa3, GSTa4, GSTm1, GSTm2, GSTm3, GSTm4, GSTp1, and GSTo1 and upregulated expression of GSTk1. The results of qRT-PCR were consistent with the results of sequencing. Conclusion GST affects lipid metabolism by participating in various biological processes such as steroid metabolism, fatty acid metabolism, and cholesterol metabolism and is closely associated with the pathogenesis of NAFLD.

Analysis of reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products / 中国临床药理学与治疗学

AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.

Safety analysis on bioequivalence studies of orally inhaled drug products in healthy Chinese subjects / 中国临床药理学与治疗学

AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.

Role of macrophages in heart failure and traditional Chinese medicine intervention / 中国中药杂志

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.

Accuracy of calculating mechanical power of ventilation by one commonly used equation.

Gattinoni's equation, [Formula: see text], now commonly used to calculate the mechanical power (MP) of ventilation. However, it calculates only inspiratory MP. In addition, the inclusion of PEEP in Gattinoni's equation raises debate because PEEP does not produce net displacement or contribute to MP. Measuring the area within the pressure-volume loop accurately reflects the MP received in a whole ventilation cycle and the MP thus obtained is not influenced by PEEP. The MP of 25 invasively ventilated patients were calculated by Gattinoni's equation and measured by integration of the areas within the pressure-volume loops of the ventilation cycles. The MP obtained from both methods were compared. The effects of PEEPs on MP were also evaluated. We found that the MP obtained from both methods were correlated by R2 = 0.75 and 0.66 at PEEP 5 and 10 cmH2O, respectively. The biases of the two methods were 3.13 (2.03 to 4.23) J/min (P < 0.0001) and - 1.23 (- 2.22 to - 0.24) J/min (P = 0.02) at PEEP 5 and 10 cmH2O, respectively. These P values suggested that both methods were significantly incongruent. When the tidal volume used was 6 ml/Kg, the MP by Gattinoni's equation at PEEP 5 and 10 cmH2O were significantly different (4.51 vs 7.21 J/min, P < 0.001), but the MP by PV loop area was not influenced by PEEPs (6.46 vs 6.47 J/min, P = 0.331). Similar results were observed across all tidal volumes. We conclude that the Gattinoni's equation is not accurate in calculating the MP of a whole ventilatory cycle and is significantly influenced by PEEP, which theoretically does not contribute to MP.

Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3+CD25+CD4+ Treg cells via the IL-2/STAT5 signaling pathway / 中国天然药物

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.

Effects of different induced abortions on women's menstrual re-fluid time, vaginal bleeding time and the incidence of postoperative intrauterine adhesion / 中国基层医药

Objective:To investigate the effects of different induced abortions on women's menstrual re-fluid time, vaginal bleeding time and the incidence of postoperative intrauterine adhesion.Methods:A total of 260 women who underwent painless abortion under ultrasound surveillance in The Second Hospital of Jiaxing from January 2019 to January 2021 were included in the ultrasound group. An additional 260 women who underwent minimally invasive endoscopic visual abortion were included in the endoscopy group. Operation-related indexes were compared between the two groups. Menstrual re-fluid time, vaginal bleeding time, postoperative abdominal pain and the incidence of postoperative intrauterine adhesion were compared between the two groups.Results:Operative time in the endoscopy group was significantly shorter than that in the ultrasound group [(3.37 ± 0.84) minutes vs. (6.59 ± 2.03) minutes, t = 23.68, P < 0.001]. The amount of intraoperative blood loss in the endoscopy group was significantly less than that in the ultrasound group [(15.87 ± 5.65) mL vs. (33.04 ± 10.44) mL, t = 23.33, P < 0.001]. Postoperative vaginal bleeding time and menstrual re-fluid time in the endoscopy group were (3.16 ± 1.58) days and (30.37 ± 6.13) days, respectively, which were significantly shorter than those in the ultrasound group [(4.23 ± 1.83) days, (32.07 ± 4.25) days, t = 7.10, 3.69, P < 0.001]. There were no significant differences in the severity and duration of postoperative abdominal pain between the two groups (both P > 0.05). Complete abortion rate in the endoscopy group was significantly higher than that in the ultrasound group [98.85% vs. 96.15%, χ2 = 3.86, P < 0.05]. The incidence of complications in the endoscopy group was significantly lower than that in the ultrasound group (2.31% vs. 5.77%, χ2 = 4.01, P < 0.05). There was no significant difference in the incidence of postoperative intrauterine adhesion between the endoscopy and ultrasound groups (1.15% vs. 3.46%, P > 0.05). Conclusion:Both minimally invasive endoscopic visual abortion and B-ultrasound-guided painless abortion have painless effects. Minimally invasive endoscopic visual abortion produces less postoperative impact, leads to better postoperative recovery, and is safer than B-ultrasound-guided painless abortion.

Application of interatrial shunt device in patients with severe pulmonary hypertension / 中国胸心血管外科临床杂志

@#Pulmonary arterial hypertension (PAH) is a severe, progressive disease leading to right ventricular failure and finally death. Lung transplantation is recommended for PAH patients who do not respond to targeted drug combination therapy or World Health Organization functional class (WHO FC) Ⅲ or Ⅳ. However, only 3% of PAH patients can recieve the lung transplantation. A novel implantable interatrial shunt device (ISD) can create a relatively fixed right-to-left shunt established by balloon atrial septostomy (BAS). The device may decompress the right sided chambers, facilitate left heart filling, improve organ perfusion and reduce the likelihood of syncope, acute pulmonary hypertensive crisis and death. The systemic oxygen transport improves despite hypoxemia. Implantation is simple, feasible and safe, and the X-ray time and operation time are short. There is no severe complication or thrombosis during the mid-term follow-up of the clinical studies and the device remained patent. The syncope symptoms, six-minute walk distance, cardiac index and systemic oxygen transport improve significantly in the patients. ISD may be currently the last alternative treatment to improve symptoms and prolong survival in currently drug-resistant patients with severe PAH.

Investigating the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of severe scald rabbits based on 16S ribosomal RNA high-throughput sequencing / 中华烧伤杂志

Objective: To investigate the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of in severe scald rabbits based on 16S ribosomal RNA (16S rRNA) high-throughput sequencing. Methods: The experimental research method was adopted. Ninety Japanese big-ear rabbits regardless gender, aged 6 to 8 months, were randomly divided into normal control group, scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group, with 18 rabbits in each group. The rabbits in normal control group were free to eat and drink, and the rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group were intragastrically administered normal saline, 0.2 g/mL Modified Sijunzi Decoction, 1.0 g/mL Modified Sijunzi Decoction, and 5.0 g/mL Modified Sijunzi Decoction, respectively for 7 days after sustaining full-thickness scalding of 30% total body surface area. On the 1st, 3rd, and 7th day after grouping, the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-10 in ileal mucosa tissue of rabbits in each group were determined by enzyme-linked immunosorbent assay, and the number of samples in each group at each time point was 6. According to the above experimental results, another 9 rabbits were selected and divided into normal control group, scald alone group and scald+medium-dose group, with 3 rabbits in each group. The grouping and treatment methods of rabbits in each group were the same as before. On the 7th day after grouping, the V3, V4 region of 16S rRNA of ileum mucosa of rabbits in three groups were sequenced by high-throughput sequencing technology. The number of quality bacteria was counted by QIME software. The classifications of phylum, class, order, family and genus of microflora were analyzed by RDP Classifier software. The α diversity (Ace, Chao1, Simpson, and Shannon indexes) and β diversity were analyzed by Illumina MiSeq sequencing technology, and the number of experiment samples in each group was 3. Data were statistically analyzed with analysis for variance of factorial design, SNK test, and Bonferroni correction. Results: Compared with that in normal control group, the levels of TNF-α of ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping and scald+medium-dose group on the 1st and 3rd day after grouping were all significantly increased (P<0.01), the levels of IL-1β in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01). Compared with that in scald alone group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping, and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+low-dose group on the 7th day after grouping and scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and scald+high-dose group on the 3rd and 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald+low-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were significantly decreased (P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and in scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald medium-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald+high-dose group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 1st day after grouping, the levels of TNF-α in ileal mucosa tissue of rabbits in scald alone group on the 3rd and 7th day after grouping and in normal control group on the 3rd day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-1β in ileal mucosa tissue of rabbits in scald alone group both on the 3rd and 7th day after grouping were significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in both scald+low-dose group and scald+high-dose group on the 7th day after grouping and scald+medium-dose group both on the 3rd and 7th day after grouping were significantly increased (P<0.05 or P<0.01), and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 3rd and 7th day after grouping and in scald+medium-dose group on the 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the level of IL-1β in ileal mucosa tissue of rabbits in scald+medium-dose group on the 7th day after grouping was significantly decreased (P<0.01), and the level of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 3rd day after grouping, the levels of TNF-α and IL-1β in ileal mucosa tissue of rabbits in scald alone group and the levels of IL-10 in ileal mucosa tissue of rabbits in normal control group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01); and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly decreased (P<0.05), and the levels of IL-1β in ileal mucosa tissue of rabbits both in scald+medium-dose group and scald+high-dose group on the 7th day after grouping were significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). On the 7th day after grouping, the high-quality sequences obtained from the microflora in ileum mucosa of rabbits in normal control group, scald alone group, and scald+medium-dose group were 96 023, 107 365, and 95 921, respectively. At the classification level of phylum, class, order, family, and genus of the microflora in ileum mucosa of rabbits in three groups were all Bacteroidetes and Firmicutes, Clostridium and Bacteroidetes, Clostridium and Bacteroidetes, Rumenobacteriaceae and Clostridium and Bacteroideaceae, Clostridium and Bacteroidetes and rumen bacteria mainly, while the percentage of microflora in each group was different. There were no significant differences in Ace, Chao1, Simpson, Shannon indices (P>0.05), and no obvious difference in β diversity of microflora in ileal mucosa tissue of rabbits among three groups. Conclusions: After severe scalding, the inflammatory response of rabbit ileal mucosa tissue is obvious and increased in a time-dependent manner. Modified Sijunzi Decoction can reduce inflammation with optimal therapeutic concentration of 1.0 g/mL. The technology of high-throughput sequencing can reflect the structural composition of the intestinal microflora accurately. The ileal microflora of the severe scald rabbit can be regulated by the administration of Modified Sijunzi Decoction.

Clinical observation of intermittently repeated application of levosimendan in the treatment of right heart failure of pulmonary hypertension / 中国药房

OBJECTIVE To observe th e efficacy and safety of intermittently repeated application of levosimendan in the treatment of right heart failure of pulmonary hypertension. METHODS A total of 70 cases of right heart failure of pulmonary hypertension were collected from the First Affiliated Hospital of Guangxi Medical University during Jan. 2019-May 2021，and then randomly divided into control group and observation group ，with 35 cases in each group.In control group ，the patients with moderate risk of classification of pulmonary hypertension were given Tadalafil tablets and Ambrisentan tablets ，while the patients with high risk were given Tadalafil tablets ，Ambrisentan tablets and Treprostinil injection ；both were given anti-right heart failure drugs at the same time. On the basis of treatment in the control group ，patients in the observation group were additionally intravenously pumped with levosimendan injection 12.5 mg，once a month ，at a rate of 0.05-0.1 μg/（kg·min），3 months in total. Response rate of therapy ，improvement of risk stratification of pulmonary hypertension after treatment ，and average pulmonary artery pressure ，six-minute walk distance （6MWD），serum level of N-terminal pro brain natriuretic peptide （NT-proBNP），right atrial pressure （RAP），oxygen saturation in mixed venous blood （SvO2），cardiac index （CI），right ventricular ejection fraction （RVEF），early diastolic tricuspid inflow velocity/early diastolic tricuspid annular velocity （E/Ea），tricuspid annular plane systolic excursion（TAPSE），right ventricular end-diastolic diameter （RVEDD），right ventricular end-systolic diameter （RVESD）before and after treatment ，and the occurrence of adverse reactions were observed in 2 groups. RESULTS The total response rate of observation group was significantly higher than control group after treatment （P＜0.05）. After treatment ，average pulmonary artery pressure，NT-proBNP level ，RAP，E/Ea，RVEDD and RVESD of 2 groups were significantly lower than before treatment ，while 6MWD，SvO2， CI， TAPSE and RVEF were significantly higher than before treatment ；NT-proBNP level and E/Ea of observation group were significantly lower than control group ， while 6MWD，CI，TAPSE and RVEF were significantly higher than control group （P＜0.05 or P＜0.01）. There was no significant difference in average pulmonary artery pressure ， risk stratification improvement cases of pulmonary hypertension ， RAP， SvO2， RVEDD， RVESD and the incidence of asymptomatic hypotension between 2 groups（P＞0.05）. CONCLUSIONS Intermittently repeated application of levosimendan can improve the function of right heart of pulmonary hypertension complicated with right heart failure and has good safety.

Microsurgical techniques and one-stage surgical treatment of chronic osteomyelitis——concept and clinical application / 中华显微外科杂志

Chronic osteomyelitis is a serious clinical problem with repeated courses and high disability rate, which seriously affects the physical and mental health of patients. Through continuous learning and summary in the process of using traditional therapies, the innovative improvements and changes had made in the treatment of osteomyelitis: Radical debridement of lesions was performed by applying the basic principles of modern bone tumor surgery. The application of microsurgical technique to transfer composite tissue flap can provide guarantee for tissue defect repair and wound closure without tension. Combined with bone grafting, local antibiotics and bone fixation, an one-stage operation has significantly improve the therapeutic effect of chronic complex osteomyelitis.

Experimental study on the regulation of subchondral bone plate osteoprotegerin/receptor activator of nuclear factor kappa-B ligand system by berberine to retard the development of osteoarthritis in rabbits / 中国骨伤

OBJECTIVE@#To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).@*METHODS@#Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation.@*RESULTS@#The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01).@*CONCLUSION@#Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.