Oxymatrine combined with rapamycin to attenuate acute cardiac allograft rejection.

Background and aim: Solid organ transplantation remains a life-saving therapeutic option for patients with end-stage organ dysfunction. Acute cellular rejection (ACR), dominated by dendritic cells (DCs) and CD4+ T cells, is a major cause of post-transplant mortality. Inhibiting DC maturation and directing the differentiation of CD4+ T cells toward immunosuppression are keys to inhibiting ACR. We propose that oxymatrine (OMT), a quinolizidine alkaloid, either alone or in combination with rapamycin (RAPA), attenuates ACR by inhibiting the mTOR-HIF-1α pathway. Methods: Graft damage was assessed using haematoxylin and eosin staining. Intragraft CD11c+ and CD4+ cell infiltrations were detected using immunohistochemical staining. The proportions of mature DCs, T helper (Th) 1, Th17, and Treg cells in the spleen; donor-specific antibody (DSA) secretion in the serum; mTOR-HIF-1α expression in the grafts; and CD4+ cells and bone marrow-derived DCs (BMDCs) were evaluated using flow cytometry. Results: OMT, either alone or in combination with RAPA, significantly alleviated pathological damage; decreased CD4+ and CD11c+ cell infiltration in cardiac allografts; reduced the proportion of mature DCs, Th1 and Th17 cells; increased the proportion of Tregs in recipient spleens; downregulated DSA production; and inhibited mTOR and HIF-1α expression in the grafts. OMT suppresses mTOR and HIF-1α expression in BMDCs and CD4+ T cells in vitro. Conclusions: Our study suggests that OMT-based therapy can significantly attenuate acute cardiac allograft rejection by inhibiting DC maturation and CD4+ T cell responses. This process may be related to the inhibition of the mTOR-HIF-1α signaling pathway by OMT.

Successful Treatment Strategy for Duplicate Inferior Vena Cava and Deep Venous Thrombosis: Filter Placement and Thrombolysis Approach.

BACKGROUND Duplicate inferior vena cava (IVC) accompanied by deep venous thrombosis is rare. The optimal treatment plan is determined according to the results of imaging, including venography. In this report, we present a case of successful treatment of a patient with duplicate IVC and deep venous thrombosis (DVT). CASE REPORT An 84-year-old man with history of hypertension was admitted to the hospital because of 4 days of moderate left lower-limb edema. A thorough examination led to the diagnosis of the DVT. The duplicate IVC was discovered during venography. As the blood from the left common iliac vein mainly flowed to the left IVC, and there were no other communicating branches before the convergence of the left and right IVCs, which was located above the 1st lumbar vertebrae body near the junction of the hepatic vein and the IVC, the strategy of placing only 1 filter in the left inferior vena cava were chosen, rather than placing 1 filter above the confluence of bilateral IVC, or placing a filter in each IVC below the level of renal veins on each side. Following that, the DVT was safely treated with thrombolysis and aspiration without the risk of pulmonary embolism. CONCLUSIONS This case report presented the complete evaluation and management of a patient with lower-limb DVT accompanied by the malformation of duplicate IVC. The filter placement strategy with duplicate IVC in the literature was summarized. We concluded that even in emergency situations, with comprehensive consideration, it is possible to perform endovascular intervention successfully and achieve satisfactory treatment results.

Study on Oxymatrine-Based Research from 2001 to 2022: A Bibliometric Analysis.

Oxymatrine is a quinolizidine alkaloid mainly derived from Kushen; it possesses various therapeutic effects, such as organ- and tissue-protective, anticancer, and antiviral effects. The research directions for oxymatrine remain broad. In order to explore the overall status of oxymatrine-based research, we carried out a bibliometric analysis to summarize the oxymatrine-based, English-written studies published in the past 22 years. In total, 267 studies were included, most of which were original. The number of annual studies slowly increased with some fluctuations. Other than China, 11 different countries conducted studies on oxymatrine; the variety in the country of origin of these publications is presented as a recently increasing trend. Many affiliates and researchers have participated in oxymatrine-based research. Various treatment mechanisms involving different oxymatrine pathways have led to research in a wide range of fields, being published in numerous journals. Two particularly popular research fields related to oxymatrine involved anticancer and anti-inflammation. From this research, we concluded that with increasing and continuous in-depth studies, more therapeutic effects and mechanisms will be elucidated, and oxymatrine may present as a viable option for the treatment of additional diseases.

Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1 / FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics / 中国临床药理学与治疗学

AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.

[Investigation and analysis of dental and jaw deformities of junior middle school students and their parents' awareness of correction in Ganzhou city].

PURPOSE: To investigate and analyze orthognathic deformities of junior middle school students in Ganzhou City and their parents' awareness of correction. METHODS: From January 2019 to December 2020, a stratified cluster sampling method was adopted to select 2 189 middle school students in Ganzhou City and an anonymous self-filling questionnaire survey was conducted. The difference between the students with and without correction of dental deformities was compared. The difference between parents of students with and without orthodontic teeth deformity was analyzed. The data were statistically analyzed with SPSS 18.0 software package. RESULTS: Among 2 189 junior high school students, the incidence of dental and jaw malformations was 54.04%, and the correction rate of dental and jaw malformations was 33.64%. The correction rate of dental deformities in girls was significantly higher than in boys(P＜0.05). The correction rate of tooth and jaw deformity in urban students was significantly higher than in rural students(P＜0.05). In terms of the students' judgment on the appearance and function of their teeth, some in the orthodontic group mentioned that their teeth were irregular, they would not intentionally cover their teeth with their hands, they cared about others' opinions on their teeth, not satisfied with their feelings about the appearance of their teeth and their teeth affected chewing or articulation were significantly higher than those in the group without orthodontic deformity(P＜0.05). In terms of students' cognition of teeth and jaw deformities, the proportion of students in the orthodontic group who did not know about the orthodontic treatment was significantly lower than that in the group without orthodontic treatment(P＜0.05). In terms of the concerns about orthodontic treatment, the percentages of the orthodontic treatment group worried about the impact of wearing orthodontic devices on eating, brushing, appearance, fear of tooth extraction and pain were significantly lower than those of the group without orthodontic treatment (P＜0.05). Bachelor degree or above educational level of parents and the proportion of working in institutions and public institutions and state-owned enterprises in the orthodontic group were significantly higher than those in the non-orthodontic group(P＜0.05). The family monthly income≥10 000 yuan, the proportion of those who thought their children need orthodontic treatment, the proportion of those who were willing to spend time to help their children with orthodontic treatment, and the proportion of those who supported to pay for orthodontic treatment for their children were significantly higher than those without orthodontic treatment(P＜0.05). The proportion of parents satisfied with their children's dental condition in the orthodontic group was significantly lower than that in the non-orthodontic group (P＜0.05). CONCLUSIONS: Junior middle school students in Ganzhou City have the characteristics of higher prevalence rate of dental and jaw malformations. The correction rate of dental and jaw malformations is significantly different between female and male students, as well as urban and rural students. The lack of cognition of students and their parents, education level of parents and family economic level may affect the demand for orthodontic treatment of dental deformities.

Efficacy of crown lengthening for restoration of maxillary anterior tooth defects.

OBJECTIVE: The appearance of the gingival tissue around the teeth is essential in the aesthetics of the anterior maxillary region of the oral cavity. Abnormalities in symmetry and contour can significantly compromise the appearance of the natural or restored dentition, so the outcome is highly relevant to treatment choice. This study evaluated the efficacy of crown lengthening for restoration of maxillary anterior tooth defects. METHODS: A total of 80 patients (87 affected teeth) diagnosed with maxillary anterior tooth loss in Ganzhou People's Hospital between May 2020 and August 2021 were retrospectively enrolled and divided into an experimental group or a reference group according to different treatment methods, with 40 cases in each group. The reference group received a post and core procedure, while the experimental group received crown lengthening plus a post and core procedure. Outcome measures included clinical efficacy, gingival periodontal-related indices, and dental aesthetics indices. RESULTS: Crown lengthening plus post and core procedure was associated with a significantly higher clinical efficacy (95.65%) versus post and core procedure alone (78.05%) (P<0.05). Postoperatively, the levels of probing depth (PD), plaque index (PLI), bleeding index (BI), and gingival index (GI) were lower in patients of the experimental group than those in the reference group (all P<0.05). Crown lengthening plus post and core procedure resulted in more Kay class I and II patients and fewer Kay class III and IV versus the post and core procedure alone (P<0.05). The position of gingival margin (PGM) and gingival recession (GR) of patients in the experimental group were higher than those in the reference group after operation (P<0.05). Logistic regression analysis showed that the morphology of broken ends, plaque control, hygiene habits, and smoking were influencing factors for maxillary anterior tooth defects (all P<0.05). Patients were more satisfied (97.50%) in the experimental group than those in the reference group (80.00%) (P<0.05). CONCLUSION: Crown lengthening improves the periodontal condition of patients with maxillary anterior tooth loss, reduces gingival sulcus bleeding, and improves dental aesthetics and patient satisfaction. Further clinical studies are required prior to clinical promotion.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Effect of Capsaicin Atomization on Cough and Swallowing Function in Patients With Hemorrhagic Stroke: A Randomized Controlled Trial.

BACKGROUND: Patients with hemorrhagic stroke have high mortality and disability rates. Nevertheless, early rehabilitation interventions can improve their outcomes. We aimed to apply capsaicin atomization as early intervention to patients with hemorrhagic stroke and explore improvements in cough and swallowing functions. METHOD: Patients with hemorrhagic stroke were randomly divided into the control group, which received routine care, and the intervention group, which underwent the capsaicin solution nebulization scheme in addition to routine care. Differences in the presence/absence of cough reflex and number of coughs in response to capsaicin, the presence/absence of swallowing reflex in response to water, the presence/absence of postswallow residue, substance P (SP) concentration, and pulmonary inflammation between the two groups were determined before and after the intervention. RESULTS: A total of 53 patients with hemorrhagic stroke were included. Results showed no statistically significant difference in cough reflex in both groups after the intervention (p > .05). The degree of cough in the intervention group was stronger than that in the control group (p = .046). No statistically significant difference was observed in the number of patients with swallowing reflex in response to water between the groups (p > .05). The presence/absence of postswallow residue of the intervention group was stronger than that of the control group (p = .032). No statistically significant difference was observed between the Glasgow Coma Scale scores of the groups after the intervention (p > .05). SP in the intervention group was significantly increased (p = .031). The Clinical Pulmonary Infection Score was significantly lower in the control group, and the difference was statistically significant (p = .028). CONCLUSIONS: Capsaicin nebulization can help enhance the number of coughs in response to capsaicin, reduce postswallow residue, and increase the level of SP in patients with hemorrhagic stroke and has a positive effect on pulmonary inflammation. This study provides intervention points for cough and swallowing rehabilitation after a hemorrhagic stroke. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21956903.

Rapamycin-induced β-Globin Family Locus Remodeling Regulates the Gene Switching Expression / 中国生物化学与分子生物学报

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

Effects of mechanical cardiopulmonary resuscitation during vertical spatial pre-hospital transport in patients with cardiac arrest: a historical cohort study / 中华危重病急救医学

OBJECTIVE@#To analyze the effect of mechanical cardiopulmonary resuscitation (CPR) on patients with cardiac arrest with the vertical spatial pre-hospital emergency transport.@*METHODS@#A retrospective cohort study was conducted. The clinical data of 102 patients with out-of-hospital cardiac arrest (OHCA) who were transferred to the emergency medicine department of Huzhou Central Hospital from the Huzhou Emergency Center from July 2019 to June 2021 were collected. Among them, the patients who performed artificial chest compression during the pre-hospital transfer from July 2019 to June 2020 served as the control group, and the patients who performed artificial-mechanical chest compression (implemented artificial chest compression first, and implemented mechanical chest compression immediately after the mechanical chest compression device was ready) during pre-hospital transfer from July 2020 to June 2021 served as the observation group. The clinical data of patients of the two groups were collected, including basic data (gender, age, etc.), pre-hospital emergency process evaluation indicators [chest compression fraction (CCF), total CPR pause time, pre-hospital transfer time, vertical spatial transfer time], and in-hospital advanced resuscitation effect evaluation indicators [initial end-expiratory partial pressure of carbon dioxide (PETCO2), rate of restoration of spontaneous circulation (ROSC), time of ROSC].@*RESULTS@#Finally, a total of 84 patients were enrolled, including 46 patients in the control group and 38 in the observation group. There was no significant difference in gender, age, whether to accept bystander resuscitation or not, initial cardiac rhythm, time-consuming pre-hospital emergency response, floor location at the time of onset, estimated vertical height, and whether there was any vertical transfer elevator/escalator, etc. between the two groups. In the evaluation of the pre-hospital emergency process, the CCF during the pre-hospital emergency treatment of patients in the observation group was significantly higher than that in the control group [69.05% (67.35%, 71.73%) vs. 61.88% (58.18%, 65.04%), P < 0.01], the total pause time of CPR was significantly shorter than that in the control group [s: 266 (214, 307) vs. 332 (257, 374), P < 0.05]. However, there was no significant difference in the pre-hospital transfer time and vertical spatial transfer time between the observation group and the control group [pre-hospital transfer time (minutes): 14.50 (12.00, 16.75) vs. 14.00 (11.00, 16.00), vertical spatial transfer time (s): 32.15±17.43 vs. 27.96±18.67, both P > 0.05]. It indicated that mechanical CPR could improve the CPR quality in the process of pre-hospital first aid, and did not affect the transfer of patients by pre-hospital emergency medical personnel. In the evaluation of the in-hospital advanced resuscitation effect, the initial PETCO2 of the patients in the observation group was significantly higher than that of the patients in the control group [mmHg (1 mmHg ≈ 0.133 kPa): 15.00 (13.25, 16.00) vs. 12.00 (11.00, 13.00), P < 0.01], the time of ROSC was significantly shorter than that in the control group (minutes: 11.00±3.25 vs. 16.64±2.54, P < 0.01), and the rate of ROSC was slightly higher than that in the control group (31.58% vs. 23.91%, P > 0.05). It indicated that continuous mechanical compression during pre-hospital transfer helped to ensure continuous high-quality CPR.@*CONCLUSIONS@#Mechanical chest compression can improve the quality of continuous CPR during the pre-hospital transfer of patients with OHCA, and improve the initial resuscitation outcome of patients.

[Effect of ultrasonic curettage combined with sodium hyaluronate gel on chronic periodontitis and its effect on inflammatory factors hs-CRP, MCP-1 and MMP-13 in gingival crevicular fluid].

PURPOSE: To investigate the effect of ultrasonic curettage combined with sodium hyaluronate gel in the treatment of chronic periodontitis (CP) and the effect on inflammatory factor hypersensitive C-reactive protein (hs-CRP), monocyte chemotactic protein 1 (MCP-1) and matrix metalloproteinase 13 (MMP-13) in gingival crevicular fluid. METHODS: A total of 102 patients with CP from October 2021 to October 2022 were selected, divided into experimental group (n=51) and control group (n=51) by random number table method. The control group received ultrasonic subgingival curetage, and the experimental group received sodium hyaluronate gel adjuvant therapy on the basis of the control group. The periodontal rehabilitation indexes, clinical efficacy and the changes of gingival crevicular fluid hs-CRP, MCP-1 and MMP-13 were compared between the two groups. The periodontal pathogens, bone metabolism indexes and the occurrence of adverse events during treatment were compared between the two groups. The data were statistically analyzed using SPSS 22.0 software package. RESULTS: After treatment, the sulcus bleeding index (SBI), gingival index (GI), plaque index (PLI), periodontal pocket depth (PD) and attachment level (AL) of the two groups were significantly lower than before treatment (P＜0.05), and even significantly lower(P＜0.05) in the experimental group. Total effective rate of the experimental group was significantly higher than that of the control group(P＜0.05). hs-CRP, MCP-1 and MMP-13 in both groups after treatment were significantly lower than before treatment(P＜0.05), and hs-CRP, MCP-1 and MMP-13 in the experimental group after treatment were significantly lower than those in the control group(P＜0.05). The detection rates of Porphyromonas gingivalis, Forsetanella and Treponema dentalis were significantly lower in both groups after treatment than before treatment (P＜0.05), and the detection rates of the above indexes in the experimental group after treatment were significantly lower than those in the control group(P＜0.05). After treatment, the C-terminal peptide(CTX) of type Ⅰ collagen was significantly lower than that before treatment, and bone gla protein(BGP) was significantly higher than that before treatment(P＜0.05). The CTX and BGP of the experimental group were significantly lower than that of the control group and significantly higher than that of the control group(P＜0.05). There was no significant difference in the incidence of total adverse reactions between the two groups(P＞0.05). CONCLUSIONS：Ultrasonic curettage combined with sodium hyaluronate gel in the treatment of CP can promote periodontal tissue rehabilitation, enhance short-term efficacy, inhibit synthesis of inflammatory factors in gingival crevicular fluid, kill periodontal pathogens, regulate bone metabolism, and is safe and reliable.

Distinguishing features of Long COVID identified through immune profiling

SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID1-3. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions1-3; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

[Effect of dimethyloxalylglycine on angiogenesis in Choke â ¡ zone of cross-zone perforator flap and its mechanism].

OBJECTIVE: To study the effect of dimethyloxalylglycine (DMOG) on angiogenesis in Choke Ⅱ zone of rats cross-zone perforator flaps and its mechanism. METHODS: One hundred and twenty-six adult male Sprague Dawley rats were randomly divided into DMOG group, YC-1 group, and control group, with 42 rats in each group. Cross-zone perforator flap model with size of 12 cm×3 cm was made on the back of rats in the three groups. DMOG group was intraperitoneally injected with DMOG (40 mg/kg) at 1 day before operation, 2 hours before operation, and 1, 2, and 3 days after operation; YC-1 group and control group were intraperitoneally injected with YC-1 (10 mg/kg) and the same amount of normal saline at the same time points, respectively. The survival of flap was observed after operation. At 7 days after operation, the survival area of flap in each group was measured and the survival rate of flap was calculated. Flap transmittance test, gelatin-lead oxide angiography, and HE staining were used to observed the angiogenesis in the Choke Ⅱ zone of flaps in each group. Immunohistochemical staining and Western blot were used to detect the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) in Choke Ⅱ zone of flaps in each group. The expressions of VEGF and HIF-1α were also determined by ELISA at 3, 5, and 7 days. RESULTS: At 7 days after operation, there was no obvious necrosis at the distal end of the flap in DMOG group, while necrosis occurred in both the control group and YC-1 group, mainly located at the distal end. The flap survival rate of DMOG group was 90.28%±1.37%, which was significantly higher than that of YC-1 group (84.28%±1.45%) and control group (85.83%±1.60%) ( P<0.05). DMOG group had more angiogenesis in Choke Ⅱ zone and the vascular structure was clear and complete. In YC-1 group and control group, the vessels in Choke Ⅱ zone was less and the vascular structure was disordered. The number of vessels was (25.56±1.29)/field in the DMOG group, which was significantly higher than that in the YC-1 group [(7.38±0.54)/field] and the control group [(14.48±0.91)/field] ( P<0.05). At 3, 5, and 7 days after operation, HIF-1α and VEGF expressions in ChokeⅡzone of DMOG group were significantly higher than those in YC-1 group and control group ( P<0.05). CONCLUSION: DMOG can promote angiogenesis in Choke Ⅱ zone, accelerate the early angiogenesis of the flap, improve the microcirculation and blood supply in the potential zone of the flap, reduce the injury of flap ischemia and hypoxia, and increase the survival rate of the flap.

Perifosine inhibits biofilm formation of Pseudomonas aeruginosa by interacting with PqsE protein / 中华预防医学杂志

To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 μg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.

Oxymatrine protects cardiac allografts by regulating immunotolerant cells.

Organ transplantation is an effective treatment strategy for patients with irreversible organ failure or congenital organ dysfunction. Oxymatrine (OMT) is a quinolizidine alkaloid with protective and anti-inflammatory effects on tissues and organs. The objective of this study was to investigate whether OMT could exert protective effects in cardiac allografts by regulating immune cells. In vitro cell proliferation and co-culture experiments were used to measure the effects of OMT on splenocyte proliferation and differentiation. In the in vivo study, C57BL/6 mice transplanted with BALB/c cardiac grafts were randomly divided into untreated, low-dose OMT treated, middle-dose OMT treated, high-dose OMT treated, and rapamycin-treated groups. Haematoxylin and eosin and immunohistochemical staining were used to assess pathological changes in the grafts, and fluorescence-activated cell sorting analysis was performed to measure the percentages of immune cells. The results showed that, in the in vitro study, OMT inhibited splenocyte proliferation, decreased the percentage of mature dendritic cells (DCs), and increased the percentage of regulatory T cells (Tregs) and regulatory B cells (Bregs). In the in vivo study, OMT exerted allograft protective effects by prolonging survival time, alleviating pathological damages to the cardiac allograft, decreasing intragraft CD3+ cell and increasing intragraft Foxp3+ cell infiltration, decreasing the percentages of mature DCs, increasing the percentages of Tregs and Bregs, and inhibiting the function of DCs. In conclusion, our study demonstrates that OMT exerted a protective effect on cardiac allografts by regulating immunotolerant cells. More in-depth studies of OMT may provide additional insight into the use of immunosuppressive drugs as a post-transplantation treatment strategy.

Uncertainty and misinterpretation over identification, quantification and transformation of reactive species generated in catalytic oxidation processes: A review.

The identification of reactive radical species using quenching and electron paramagnetic resonance (EPR) tests has attracted extensive attention, but some mistakes or misinterpretations are often present in recent literature. This review aims to clarify the corresponding issues through surveying literature, including the uncertainty about the identity of radicals in the bulk solution or adsorbed on the catalyst surface in quenching tests, selection of proper scavengers, data explanation for incomplete inhibition, the inconsistent results between quenching and EPR tests (e.g., SO4•- is predominant in quenching test while the signal of •OH predominates in EPR test), and the incorrect identification of EPR signals (e.g., SO4•- is identified by indiscernible or incorrect signals). In addition, this review outlines the transformation of radicals for better tracing the origin of radicals. It is anticipated that this review can help in avoiding mistakes while investigating catalytic oxidative mechanism with quenching and EPR tests.

Advance in Neural Control in Eccentric Exercise (review) / 中国康复理论与实践

The nervous system controls eccentric exercise in a special way. During eccentric exercise, excitability increases in cortex, and inhibition decreases, causing excitability decrease in spinal cords. In another hand, increased cortical excitability results in extra excitatory compensation for spinal inhibition. The excitability of the corticospinal pathway depends on the balance between excitability and inhibition of the spinal cord level finally, which usually decreases. Many factors, such as the intensity of contraction, can affect the balance of corticospinal excitability. There is a cross-over effect in eccentric exercise, which promotes corticospinal excitability in untrained limbs. However, the effects and mechanisms of muscle length, fatigue and training duration are still unclear, and current researches have focused in the healthy populations. More researches are needed to explore the effects of eccentric exercise on ill populations.

Sialic acid-binding immunoglobulin-like lectin 9 as a potential therapeutic target for chronic obstructive pulmonary disease / 中华医学杂志(英文版)

Chronic obstructive pulmonary disease (COPD) has become the third-leading cause of death worldwide, which is a severe economic burden to the healthcare system. Chronic bronchitis is the most common condition that contributes to COPD, both locally and systemically. Neutrophilic inflammation predominates in the COPD airway wall and lumen. Logically, repression of neutrophilia is an essential fashion to COPD treatment. However, currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects. Thus, there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 is a member of the Siglec cell surface immunoglobulin family. It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes. Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils. Furthermore, administration of antibody to Siglec-E, mouse functional ortholog of Siglec-9, restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo. Given the critical role that neutrophils play in chronic bronchitis and emphysema, targeting Siglec-9 could be beneficial for the treatment of COPD, asthma, fibrosis, and related chronic inflammatory lung diseases.

Development of a simple in vitro assay to identify and evaluate nucleotide analogs against SARS-CoV-2 RNA-dependent RNA polymerase

Nucleotide analogs targeting viral RNA polymerase have been approved to be an effective strategy for antiviral treatment and are attracting antiviral drugs to combat the current SARS-CoV-2 pandemic. In this report, we develop a robust in vitro nonradioactive primer extension assay to evaluate the incorporation efficiency of nucleotide analog by SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) quantitively. Our results show that many nucleotide analogs can be incorporated into RNA by SARS-CoV-2 RdRp, and that the incorporation of some of them leads to chain termination. The discrimination values of nucleotide analog over those of natural nucleotide were measured to evaluate the incorporation efficiency of nucleotide analog by RdRp. We found that the incorporation efficiency of Remdesivir-TP is higher than ATP, and we did not observe chain termination or delayed chain termination caused by single Remdesivir-TP incorporation, while multiple incorporations of Remdesivir-TP caused chain termination in our assay condition. The incorporation efficiency of Ribavirin-TP and Favipiravir-TP is very low either as ATP or GTP analogs, which suggested that mutagenesis may not be the mechanism of action of those two drugs against SARS-CoV-2. Incorporation of Sofosbuvir-TP is also very low suggesting that sofosbuvir may not be very effective in treating SARS-CoV-2 infection. As a comparison, 2-C-Methyl-GTP can be incorporated into RNA efficiently, and the derivative of 2-C-Methyl-GTP may have therapeutic application in treating SARS-CoV-2 infection. This report provides a simple screening method that should be useful in evaluating nucleotide-based drugs targeting SARS-CoV-2 RdRp, and for studying the mechanism of action of selected nucleotide analog.

Anti-aging role of Chinese herbel medicine: an overview of scientific evidence from 2008 to 2018.

The aging of the population has become a global health problem. It is an important risk factor for major diseases such as cardiovascular disease, Alzheimer's disease, Parkinson's disease, and cancer. Presently, there is no definite and effective anti-aging treatment. Chinese herbal medicine has a long history of application and is often used for aging-related diseases in China. A large number of clinical and preclinical studies on the anti-aging effect of Chinese herbal medicine has been performed. Through literature research, we reviewed the anti-aging clinical research of Chinese herbal medicine and preclinical research of Chinese herbal medicine monomers, components, extracts, and compounds, and their mechanisms. Results from preclinical studies have shown that Chinese herbal medicines have beneficial anti-aging effects. The mechanism mainly includes anti-oxidative stress, anti-inflammatory, neuroprotection, apoptosis and mitochondrial function regulation, etc. However, more detailed high-quality clinical trials are required for future investigation of the anti-aging effects of Chinese herbal medicines.