Meta-analysis of efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery / 中国药房

OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） and cohort studies about aspirin （trial group） versus other anticoagulants （control group） were collected during the inception and June 1st， 2023. After literature screening， data extraction and quality evaluation， the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included， involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis （DVT） [RR＝1.81， 95%CI（1.36， 2.40）， P＜0.000 1] and postoperative pulmonary embolism （PE） [RR＝1.55， 95%CI（1.01， 2.40）， P＝0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding， postoperative surgical site infection， all-cause death， or any bleeding after surgery between 2 groups. In the cohort study， the incidence of any bleeding in trial group was significantly lower than control group [RR＝0.71，95%CI （0.64， 0.79）， P＜0.000 1]， while the differences in other indicators were not statistically significant （P＞0.05）. The results of subgroup analysis based on different anticoagulants showed that in RCT， the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin （LMWH） were significantly lower than using aspirin （P＜0.05）； in the cohort study， the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants （DOAC） than using aspirin （P＜0.05）. There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH （P＞0.05） in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery， but its efficacy may not be as good as other anticoagulants. After orthopedic surgery， other anticoagulants should be preferred to prevent venous thromboembolism， and aspirin should be carefully considered.

Progress of chronic obstructive pulmonary disease patients with different muscle mass levels / 公共卫生与预防医学

Objective To investigate the difference of the disease progression in patients with chronic obstructive pulmonary disease (COPD) with different muscle mass levels and the influence of related factors on the disease progression. Methods A total of 308 newly diagnosed patients with COPD from February 2021 to February 2022 were selected for this study. All patients were below moderate COPD. The patients were divided into two groups according to their muscle mass levels: sarcopenia group (98 cases) and control group (210 cases). The diagnostic criteria for sarcopenia were based on sarcopenia diagnostic thresholds: RSMI 2 in men and 2 for women. All subjects were followed up for 4 months to observe the progress of the patient's condition. The correlation between the muscle mass level and pulmonary function level, as well as the results of 6-minute walking test and CAT score was evaluated, and the influence of muscle mass level on the patient's disease progress was analyzed. At the same time, the potential influence of related factors (body fat rate, vitamin D level, etc.) on the condition of patients with different muscle mass levels was discussed. SPSS 19.0 software was used to perform statistical analysis. Results Under the same treatment intervention, the baseline and follow-up lung function improvement levels of patients in the sarcopenia group were lower than those in the control group, and the difference was statistically significant (P<0.05). At the same time, the baseline and follow-up 6-minute walk test results of the patients in the sarcopenia group were also worse than those of the control group, and the difference was statistically significant (P<0.05). Further correlation analysis was carried out between the patient's muscle mass level and the post-treatment pulmonary function indicators and 6MWD test level. The results showed that the muscle mass level was positively correlated with several pulmonary function indicators (FEV1, FEV1% predict) and 6MWD (both P<0.05). Considering the possible influence of other factors on the control and progress of the patient's condition, the present study used follow-up CAT score results to distinguish the prognosis of the patient's condition improvement, and used improvement and non-improvement as dependent variables to analyze the influence of various potential influencing factors. The results of regression model analysis showed that lower baseline muscle mass, women, lower body fat percentage, and lower vitamin D level were the main risk factors. Conclusion Under the same treatment condition, COPD patients with different muscle mass levels improve more slowly when complicated with sarcopenia and have poor prognosis. Women, lower body fat percentage and lower vitamin D level are potential risk factors for poor prognosis.

Exploring Scientific Connotation of "Fried Charcoal Survivability" of Lonicerae Japonicae Flos Based on Color-composition Correlation / 中国实验方剂学杂志

ObjectiveTo explore the scientific connotation of fried charcoal survivability of Lonicerae Japonicae Flos（LJF） by analyzing the correlation between the color change and the intrinsic components during the processing of LJF Carbonisata（LJFC）， and taking pH， charcoal adsorption and microscopic characteristics as indexes. MethodLJFC samples with different degrees of processing were prepared according to the stir-frying time of 0.0， 1.5， 3.0， 4.5， 6.0， 7.5， 9.0， 10.5 min（numbered S1-S8）， and the contents of gallic acid， chlorogenic acid， cryptochlorogenic acid， rutin， luteoloside， isochlorogenic acid A and isochlorogenic acid C were determined by high performance liquid chromatography（HPLC）， and the L*（brightness）， a*（red-greenness） and b*（yellow-blueness） of LJFC samples with different degrees of processing were determined by spectrophotometer， and the correlation analysis and principal component analysis（PCA） between the contents of seven representative components and the color of the samples were carried out by SPSS 26. 0 and SIMCA-P 14.1. Then pH， adsorption force and characteristic structure of different samples of LJFC were detected and the processing pattern of LJFC was analyzed. ResultThe results of quantitative analysis revealed that the contents of luteoloside， rutin， chlorogenic acid and isochlorogenic acid A gradually decreased， and the contents of cryptochlorogenic acid， isochlorogenic acid C and gallic acid firstly increased and then decreased. The L* and b* of the sample powders decreased， and a* showed a trend of increasing and then decreasing. The L* and b* were positively correlated with the contents of chlorogenic acid， rutin， luteoloside， isochlorogenic acid A， b* was positively correlated with the content of gallic acid， and a* was positively correlated with the contents of cryptochlorogenic acid and isochlorogenic acid C. PCA revealed that samples could be clearly divided into 3 groups， S1-S2 as one group， S3-S5 as one group， and S6-S8 as one group， with S3 having the highest score. The results of regression analysis showed that only isochlorogenic acid C could be used to predict the contents of components by colorimetric values combined with regression equations. Physicochemical analysis showed that pH of LJFC increased with the increase of degree of charcoal stir-frying， while adsorption force showed a tendency of increasing and then decreasing， with the highest adsorption force in the S5 sample， and the non-glandular hairs， calcium oxalate clusters and pollen grains had a varying degree of decreasing with the deepening of processing degree， and the microstructures of S6-S8 samples were obviously charred with pollen grains almost invisible. ConclusionThe changes in chemical composition and color characteristics of LJFC during the processing have certain correlations， combined with the changes in physicochemical properties， S5 sample is found to be the optimal processed products， which can provide a reference for the processing standardization and quality evaluation of LJFC， and enrich the scientific connotation of fried charcoal survivability of LJF.

Comparison on Ameliorating Effect of Arisaematis Rhizoma and Arisaematis Rhizoma Preparatum on Allergic Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg-1） and ARP （1.2， 0.3 g∙kg-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

Directed differentiation of human induced pluripotent stem cells into midbrain / 南方医科大学学报

OBJECTIVE@#To establish an efficient protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into functional midbrain dopaminergic progenitor cells (DAPs) in vitro.@*METHODS@#hiPSCs were induced to differentiate into DAPs in two developmental stages. In the first stage (the first 13 days), hiPSCs were induced into intermediate cells morphologically similar to primitive neuroepithelial cells (NECs) in neural induction medium containing a combination of small molecule compounds. In the second stage, the intermediate cells were further induced in neural differentiation medium until day 28 to obtain DAPs. After CM-DiI staining, the induced DAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of rat models of Parkinson's disease (PD). Eight weeks after transplantation, the motor behaviors of PD rats was evaluated. Immunofluorescence assay of brain sections of the rats was performed at 2 weeks after transplantation to observe the survival, migration and differentiation of the transplanted cells in the host brain microenvironment.@*RESULTS@#hiPSCs passaged stably on Matrigel showed a normal diploid karyotype, expressed the pluripotency markers OCT4, SOX2, and Nanog, and were positive for alkaline phosphatase. The primitive neuroepithelial cells obtained on day 13 formed dense cell colonies in the form of neural rosettes and expressed the neuroepithelial markers (SOX2, Nestin, and PAX6, 91.3%-92.8%). The DAPs on day 28 highly expressed the specific markers (TH, FOXA2, LMX1A and NURR1, 93.3-96.7%). In rat models of PD, the hiPSCs-DAPs survived and differentiated into TH+, FOXA2+ and Tuj1+ neurons at 2 weeks after transplantation. Eight weeks after transplantation, the motor function of PD rats was significantly improved as shown by water maze test (P < 0.0001) and apomorphine-induced rotation test (P < 0.0001) compared with rats receiving vehicle injection.@*CONCLUSION@#HiPSCs can be effectively induced to differentiate into DAPs capable of differentiating into functional neurons both in vivo and in vitro. In rat models of PD, the transplanted hiPSCs-DAPs can survive for more than 8 weeks in the MFB and differentiate into multiple functional neurocytes to ameliorate neurological deficits of the rats, suggesting the potential value of hiPSCs-DAPs transplantation for treatment of neurological diseases.

TRPV1 participates in the protective effect of propolis on colonic tissue of ulcerative colitis / 中南大学学报(医学版)

OBJECTIVES@#Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1.@*METHODS@#Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence.@*RESULTS@#The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment.@*CONCLUSIONS@#WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

LC-MS analysis of 2-(2-phenylethyl) chromones in sodium chloride-treated suspension cells of Aquilaria sinensis / 中国中药杂志

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 μm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.

Association between clinical phenotypes of hypertrophic cardiomyopathy and Ca2+ gene variation gene variation / 中华心血管病杂志

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca2+ gene variant group (only 1 Ca2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca2+ gene variation (Ca2+ gene variation group). Compared with gene negative group, patients in Ca2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca2+ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca2+ gene variation.

Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center / 中华心血管病杂志

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

Modified Wuhutang Alleviates Airway Inflammation and Down-regulates Expression of Muc5AC， STAT3， NF-κB， and NLRP3 in Lung Tissues of RSV-infected Asthmatic Mice / 中国实验方剂学杂志

ObjectiveTo explore effect of modified Wuhutang on airway inflammation and expression of mucin （Muc） 5AC， signal transducer and activator of transcription 3 （STAT3）， nuclear factor kappa B （NF-κB）， and NOD-like receptor thermal protein domain associated protein 3 （NLRP3） in respiratory syncytial virus （RSV）-infected asthmatic mice. MethodSeventy male BALB/c mice of 6-8 weeks old were randomized into normal control （CON）， asthma （ovalbumin， OVA）， RSV infection-induced asthma （OVA+RSV）， high-， medium-， and low-dose （4.08， 2.04， 1.02 g·kg-1·d-1， respectively） modified Wuhutang， and dexamethasone （Dxms， 0.1 g·kg-1d-1） groups （n=10）. The model of asthma was established by sensitization and atomization inhalation with OVA. The RSV infection-induced asthma model was established by three consecutive RSV nasal infusions （1.0 × 106 PFU·mL-1， 50 μL）. Wuhutang was administrated by gavage， and Dxms by intraperitoneal injection. The CON group was given the same amount of normal saline by gavage. The mice were anesthetized with 2.5% pentobarbital sodium 24 h after the last administration， and then the lung tissue was stained by hematoxylin-eosin （HE） and Van Gieson （VG） for observation of airway inflammation. The immunohistochemical assay was employed to detect the expression of Muc5AC. Western blot was employed to determine the protein levels of phosphorylated （p）-STAT3， STAT3， p-NF-κB， NF-κB， and NLRP3. ResultCompared with the CON group， the OVA group presented airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition. The OVA+RSV group showed severer airway inflammatory cell infiltration and tissue hyperemia and edema than the OVA group. Compared with the OVA+RSV group， modified Wuhutang alleviated the airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition， and the high-dose group had the best performance. Compared with the CON group， the OVA group and the OVA+RSV group showed increased expression level of Muc5AC （P<0.01）. Compared with the OVA+RSV group， modified Wuhutang reduced the expression level of Muc5AC， and the reduction was significant in the high-dose group （P<0.05）. Compared with the high-dose modified Wuhutang group， Dxms lowered the expression level of Muc5AC （P<0.05）. Compared with the CON group， the OVA and OVA+RSV groups showed up-regulated protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.05， P<0.01）. Compared with the OVA+RSV group， modified Wuhutang down-regulated the protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.01）. Compared with the high-dose modified Wuhutang group， the Dxms group showed up-regulated levels of p-STAT3， p-NF-κB proteins （P<0.01）. ConclusionModified Wuhutang can reduce airway inflammation and down-regulate the expression of Muc5AC， p-STAT3， p-NF-κB， and NLRP3 in RSV-infected asthmatic mice， which suggests that Wuhutang reduces airway inflammation in RSV-infected asthma by regulating the STAT3/NF-κB signaling pathway.

Long-term outcomes of definitive radiotherapy-based comprehensive treatment for inoperable stage I-III non-metastatic pancreatic cancer / 中华放射肿瘤学杂志

Objective:To analyze long-term outcomes of inoperable non-metastatic pancreatic cancer patients treated with definitive radiotherapy-based comprehensive treatment.Methods:Clinical data of 168 patients with medically unfit, refusal to surgery or inoperable non-metastatic pancreatic cancer treated with radiotherapy-based comprehensive treatment in PLA General Hospital between January 2016 and December 2020 were retrospectively analyzed. Survival outcomes,prognostic factors and patterns of treatment failure were analyzed in the radiotherapy ( n=95) and combined chemoradiotherapy ( n=73) groups. The survival analysis was conducted by Kaplan-Meier method. The survival curve was compared by log-rank test. Independent prognostic factors were identified by Cox proportional harzard model. Results:With a median follow-up of 20.2 months in the entire group, the median overall survival (OS) and median progression-free survival (PFS) were 18.0 and 12.3 months. The corresponding median OS and median PFS after receiving radiotherapy were 14.3 and 7.7 months. The 1-, 2-and 3-year OS rates were 72.1%, 36.6% and 21.5%, and the 1- and 2-year local control rates were 82.6% and 64.3%, respectively. The median OS for stage Ⅰ, stage Ⅱ and stage III were 27.1, 18.0 and 17.0 months, respectively. There was no significant difference in the median OS of patients with localized disease (stage Ⅰ-Ⅱ) between the radiotherapy and combined chemoradiotherapy groups (21.1 vs. 20.4 months, P=0.470). In patients with locally advanced disease (stage Ⅲ), combined chemoradiotherapy group showed better median OS compared with radiotherapy group (19.2 vs. 13.8 months, P=0.004). Clinical stage, CA19-9 before radiotherapy, comprehensive treatment and biological effective dose (BED 10) were identified as the independent prognostic factors for OS ( P=0.032, 0.011, 0.003 and 0.014). The cumulative 1- and 2-year actuarial rates of treatment failure, local-regional recurrence and distant metastasis were 48% and 74.4%, 15.0% and 27.4%, 23.6% and 33.1%, respectively. Liver metastasis (16.1%, 27/168) and local recurrence (11.9%, 20/168) were the primary patterns of treatment failure. Conclusions:Definitive radiotherapy-based comprehensive treatment effectively prolongs long-term survival in patients with inoperable non-metastatic pancreatic cancer. Definitive radiotherapy can be an alternative treatment option with curative intent for patients with localized pancreatic cancer who are medically unfit or refuse to undergo surgery. The combination of radiotherapy and chemotherapy remains an effective treatment choice for locally advanced unresectable pancreatic cancer.

A preliminary study of apoptosis in tongue squamous cell carcinoma cells induced by hyperthermia via downregulation of Notch1/Jagged1/Hes1 / 中华放射肿瘤学杂志

Objective:To observe the optimal time interval of multiple short-term hyperthermia in tongue squamous carcinoma Cal-27 cells, and investigate the role of Notch signaling pathway in hyperthermia-induced apoptosis of Cal-27 cells.Methods:Cal-27 cells were placed into a 42℃ incubator for 45 min, and the second hyperthermia was performed at 6 h,12 h, 24 h, 48 h and 72 h later, respectively. Cell proliferation capacity was detected by CCK-8 assay at 0 h, 12 h and 24 h after the end of hyperthermia. After determining the optimal time interval of hyperthermia, multiple cycles of hyperthermia were performed, and the effects of hyperthermia on the proliferation and apoptosis of Cal-27 cells were detected by CCK-8 assay and flow cytometry, respectively. The changes in the expression of Notch1, Jagged1 and hairy and enhancer of split homolog-1 (Hes1) mRNA and proteins were analyzed by real-time reverse transcription PCR (qRT-PCR) and Western blot. All data were expressed as mean±SD. Two-group comparison was performed by one-way ANOVA.Results:Hyperthermia at 42℃ for 45 min every 12 h consistently inhibited the proliferation of Cal-27 cells ( P<0.05). Compared with the control group, hyperthermia in the experiment group significantly inhibited the proliferation and induced the apoptosis of Cal-27 cells after 7 cycles of hyperthermia ( P<0.05), and the expression levels of Notch1, Jagged1 and Hes1 mRNA and proteins in the hyperthermia group were significantly down-regulated (all P<0.05). Conclusions:The optimal time interval of hyperthermia to inhibit the proliferation of tongue squamous cells carcinoma Cal-27 cells is 12 h. Hyperthermia might induce the apoptosis of Cal-27 cells by inhibiting the Notch signaling pathway.

A study of the effect of scanning center on the performance of organ dose modulation in head CT / 中华放射医学与防护杂志

Objective:To investigate the effect of different scanning centers on eye lens dose, image quality, and the dose reduction rate when using the organ dose modulation (ODM) technique in head CT.Methods:The porus acusticus externus of the head phantom was considered the scanning isocenter. The ODM was initiated and the spiral scans were performed at the scanning centers with the height of porus acusticus externus and its upper and lower 2, 4, and 6 cm, respectively. The scanning range was from the top of the head to the base of the head. Three thermoluminescent dosimeters (TLD) were placed on the surface of two eyes at each scan and the average measurement value was regarded as the radiation dose to the eye lens. The volume CT dose index (CTDI vol) and dose length product (DLP) were recorded. The scans were repeated with no ODM and the dose reduction rates at each scanning center were calculated. The regions of interest (ROI) in each group of images with ODM were drawn and the noise (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated. Results:Compared with the isocenter, the maximum change rates of CTDI vol and DLP in each scanning center were 2.46% and 2.43%, respectively. The eye lens dose increased as the scanning centre moving upwars (i.e. the bed dropping) by 39.02% at the position of 6 cm above the isocenter and decreased by 35.91% at the position of 6 cm below the isocenter. With the seven groups of scanning centers, the reduction rates of CTDI vol and DLP caused by ODM were 7.95%-8.61%, 7.91%-8.61% respectively, and the difference in the reduction rate of each dose value was not statistically significant( P>0.05). The reduction rate for eye lens dose ranged from 18.09% to 26.14%, with the highest reduction rate at the position of 4 cm above the isocentre and the second rate at the isocentre (24.73%). The difference in the rate of reduction at each scanning center was statistically significant( t=0.13, P<0.05). As the scanning center moved up, the SD of the eye region decreased and the SNR increased, and the highest CNR at the isocentre was 239.79. The SD and SNR of the brain parenchyma region were 6.85-7.96 and 3.08-4.19 respectively, and the highest CNR at the isocentre was 244.79. Conclusions:When ODM technique is used in head CT, the scan centre has a significant effect on the eye lens dose and image quality. Meanwhile, the reduction rate of the eye lens dose caused by ODM is also affected. Therefore, porus acusticus externus is recommended as the scanning center in head CT.

Construction of a porcine model of ischemia with non-obstructive coronary artery and assessment by CT myocardial perfusion imaging combined with coronary CT angiography / 中华放射学杂志

Objective:To construct a porcine model of ischemia with non-obstructive coronary artery (INOCA) and explore the diagnostic value of a one-stop noninvasive method including CT myocardial perfusion imaging (CT-MPI) and coronary CT angiography (CCTA).Methods:Twelve swines were divided into the experimental group (9) and the normal group (3). Coronary microvascular dysfunction (CMD) porcine model was constructed in the experimental group by inducing diabetes mellitus, chronic kidney disease, and hypercholesterolemia. Invasive coronary angiography (ICA) and functional examination were performed on all 7+3 trial swines to clarify the INOCA diagnosis after completion of the modeling. Then, CT-MPI and CCTA were performed on all individuals to explore the CT-MPI and CCTA characteristics of INOCA porcine models. CT-MPI parameters, including myocardial blood flow (MBF), and myocardial blood volume (MBV) in rest and stress conditions, and CCTA parameters, including severity of stenosis and CAD-RADS, were analyzed.Results:ICA and functional tests showed that all swines in the experimental group met the diagnostic criteria for INOCA, which meant that INOCA porcine model was constructed successfully. CCTA results confirmed that there was no obstructive coronary stenosis in all 10 swines which were examined, which was consistent with ICA findings. CT-MPI results demonstrated that the mean MBF values, as well as the mean MBV values, in the rest and stress condition of each swines in the experimental group were lower than those of the control group. In contrast to the control group, the mean MBF and MBV values of swines in the experimental group in stress condition were generally lower than those in resting condition.Conclusions:In this study, a porcine model of CMD is successfully constructed by inducing hypercholesterolemia+diabetes mellitus+chronic kidney disease. ICA and invasive functional tests show that this CMD model meet the diagnostic criteria for INOCA. It has been confirmed that one-stop CT multimodality examination including CT-MPI and CCTA can be used for the diagnosis of INOCA as a noninvasive diagnostic method.

MRI susceptibility weighted imaging for monitoring vertebral development trajectory in second-third trimester fetuses / 中华放射学杂志

Objective:To measure the morphological parameters of the fetal vertebral centrum ossification centers (COC) in the second-third trimester using MRI susceptibility weighted imaging (SWI), and to explore the growth and development trajectory of the vertebrae.Methods:Fetus in the second-third trimester with normal vertebrae development were prospectively and continuously included in Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2015 to December 2021, and the SWI scanning of fetal spine was performed. The following morphometric parameters of the C4, T6, L3, S1 vertebrae COC were measured, including sagittal diameter, transverse diameter, height, cross-sectional area and volume. The linear and nonlinear regression analysis was used to derive the best-fit curve for each parameters and gestational age.Results:A total of 112 fetuses were recruited with gestatonal age 21-39 (29.4±3.9) weeks, including 30 cases of C4, 58 cases of T6, 92 cases of L3, 62 cases of S1. Fetal spine in utero with global curvature was kyphosis, presenting two primary curves (thoracic and sacral kyphosis). The morphological parameters sagittal diameter, transverse diameter, height, cross-sectional area and volume of C4 followed the quadratic polynomial rule during 25 to 38 weeks (R 2=0.938, 0.943, 0.952, 0.957, 0.982). During 21 to 38 weeks, the sagittal diameter, transverse diameter and height of the T6 followed the exponential growth pattern (R 2=0.915, 0.923, 0.849) and the growth of the area and volume followed the quadratic polynomial growth pattern (R 2=0.943, 0.961). The L3 followed the quadratic polynomial rule during 21 to 39 weeks (R 2=0.910, 0.916, 0.914, 0.942, 0.948) The sagittal diameter, transverse diameter and height of the S1 followed the linear growth pattern (R 2=0.905, 0.911, 0.922) and the area and volume followed the quadratic polynomial growth pattern (R 2=0.930, 0.964) during 23 to 39 weeks. Conclusions:The growth and development of C4, T6, L3 and S1 COC of fetus in the second-third trimester has a good correlation with gestational age. The growth of fetal vertebral COC in the early stage is slow, but with the growth of gestational age, the growth rate of vertebral bodies accelerates.

Correlation between memory B cells and bone erosion in rheumatoid arthritis / 中华风湿病学杂志

Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.

Effect of echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation on the Lown classification in patients with hypertrophic obstructive cardiomyopathy / 中华超声影像学杂志

Objective:To investigate the effect of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) guided by echocardiography on the Lown classification of ventricular arrhythmias in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods:A total of 85 patients with HOCM who received PIMSRA treatment at Xijing Hospital of Air Force Military Medical University from May 2017 to October 2019 were retrospectively selected. All patients underwent 24-hour Holter examinations before and 1 year after PIMSRA to obtain parameters related to Lown classification. The changes in Lown grades after PIMSRA were analyzed. The patients were divided into improved group and unimproved group according to whether there was significant improvement in Lowen′s grades, and the difference of the parameters related were compared. The influencing factors of the changes in Lown classification were analyzed.Results:Compared with before PIMSRA, there was a significant improvement in the Lown classification after PIMSRA ( P=0.001). The patients with Lown grade Ⅰ increased significantly ( P=0.001), and the patients with grade Ⅲ decreased significantly ( P=0.005). There were no significant changes in patients with Lown grades 0, Ⅱ, and Ⅳ (all P>0.05). The proportion of patients with family history of hypertrophic cardiomyopathy (HCM), the baseline Lown classes, the reduction rate of the maximum left ventricular wall thickness and the reduction rate of the provocative left ventricular outflow tract gradient (LVOTG) were higher in the improved group than the unimproved group (all P<0.05). Multivariate Logistic regression results showed that HCM family history ( OR=3.95, 95% CI=1.34-11.64, P=0.013), baseline Lown classes ( OR=2.01, 95% CI=1.25-3.22, P=0.004) and the reduction rate of the provocative LVOTG gradient ( OR=1.02, 95% CI=1.00-1.04, P=0.041) were independent factors of postoperative Lown classification improvement. Conclusions:The Lown classes of HOCM patients after PIMSRA is significantly improved.HCM family history, the baseline Lown classes, and the reduction rate of postoperative provocative LVOTG are independent influencing factors for the improvement of Lown grade.

A follow-up study of percutaneous intramyocardial septal radiofrequency ablation in the treatment of obstructive hypertrophic cardiomyopathy with mild septal hypertrophy / 中华超声影像学杂志

Objective:To evaluate the clinical efficacy of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in the treatment of obstructive hypertrophic cardiomyopathy (HOCM) with mild septal hypertrophy.Methods:Forty-five HOCM patients with mild septal hypertrophy (the maximal left ventricular wall thickness is 15-19 mm) who were treated with PIMSRA between November 2016 to February 2021 in the Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Military Medical University were enrolled, and their clinical datas were collected and analyzed. The clinical symptoms and NYHA functional class before operation, 6 months and 1 year after operation were collected. Interventricular septum thickness, left ventricular outflow tract pressure gradient, left ventricular outflow tract diameter, mitral regurgitation, left ventricular systolic and diastolic function were evaluated by transthoracic echocardiography before operation, 6 months and 1 year after operation, intraoperative complications were monitored and recorded. Postoperative arrhythmias were monitored by routine 12 lead ECG and 24-hour ambulatory ECG.Results:All patients successfully completed PIMSRA procedure.No clinical adverse events such as death, bleeding and stroke occurred during and around the operation.No left bundle branch block, complete atrioventricular block and malignant arrhythmia occurred after the operation. All patients did not need permanent pacemaker implantation.NYHA functional class and clinical symptoms of patients were significantly improved after 6 months compared with values before operation (all P<0.001, respectively), it remained stable for 1 year after operation; Anterior interventricular septum, posterior interventricular septum, maximal left ventricular wall thickness all significantly decreased (all P<0.001, respectively), left ventricular outflow tract diameter widened ( P<0.001), continuous improvement 1 year after operation; left ventricular outflow tract gradient and provoked left ventricular outflow tract gradient all significantly decreased, mitral regurgitation decreased and SAM classification reduced after 6 months compared with values before operation (all P<0.001, respectively); left ventricular end-diastolic diameter widened and left atrial diameter decreased (all P<0.001, respectively), it remained stable for 1 year after operation. Left atrial volume index decreased ( P<0.001), with continuous improvement 1 year after operation; The ratio of early diastolic mitral valve velocity to early diastolic mitral annulus velocity (E/e′) decreased ( P=0.001), it remained stable for 1 year after operation. There were no significant differences in left ventricular end diastolic volume, left ventricular end systolic volume and left ventricular ejection fraction among the three groups (all P>0.05). Conclusions:PIMSRA is effective in the treatment of obstructive hypertrophic cardiomyopathy with mild ventricular septal hypertrophy.

Progress in application of suture anchor in rotator cuff injury / 中国医师杂志

Rotator cuff injury is the most important cause of shoulder joint pain and dysfunction. In recent years, the incidence of rotator cuff injuries has gradually increased, reaching 30%-50% in people >50 years old. In the clinical treatment of rotator cuff injuries, suture anchors are widely used to fix the tendon to the bone and keep it in place without loosening or moderate tension until physiological healing is completed. The materials of suture anchors are constantly updated in clinical practice and have undergone the evolution of metal suture anchors, biodegradable suture anchors, biostable suture anchors, biocomposite suture anchors, and all suture anchors.This article reviews the advantages and disadvantages of anchors of various materials reported in domestic and foreign literatures.