Effect of Ermiaosan on Expression of Th17/Treg Cells in DBA/1 Mice with Collagen-induced Arthritis / 中国实验方剂学杂志

ObjectiveTo observe the effect of classic prescription Ermiaosan （EMS） on the differentiation of T helper 17 （Th17） /regulatory T （Treg） cells in collagen-induced arthritis （CIA） DBA/1 mice. MethodDBA/1 mice were randomized into normal group， CIA group， EMS （5.4 g·kg-1） group， and methotrexate （MTX，0.5 mg·kg-1） group according to the body weight. DBA/1 mice in CIA group， EMS group， and MTX group were immunized with equal volume of bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and were immunized with equal volume of bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21st day to induce CIA. On the day of the secondary immunization， intragastric administration started and lasted 28 days （three times/week for MTX group， and once/day for other groups）. The symptoms of CIA mice such as joint redness and swelling were observed from the 22nd day， and the arthritis was scored. After the sampling on the 49th day， synovitis of CIA mice was observed based on hematoxylin-eosin （HE） staining. Double-labeling immunofluorescence （IF） method was used to detect the expression of Th17 cell marker IL-17 and Treg cell marker forkhead transcription factor P3 （FoxP3） in CD4+T cells in CIA mouse joints. The proportion of Th17 and Treg cells in the spleen and lymph nodes of mice was detected by flow cytometry. ResultCompared with the normal group， CIA group had obvious synovitis， disordered joint structure， severely damaged articular cartilage and bone， serious bone erosion （P<0.01）， high Th17/Treg value in joint tissue （P<0.01）， high proportion of Th17 cells in spleen and lymph nodes （P<0.01）， and low proportion of Treg cells （P<0.01）. Compared with CIA group， EMS group and MTX group had normal joint structure， mild bone erosion and bone destruction， complete and smooth joint surface， low Th17/Treg value （P<0.01）， low proportion of Th17 cells in spleen and lymph nodes （P<0.01）， and high proportion of Treg cells in spleen and lymph nodes （P<0.01）. ConclusionEMS regulates the balance of Th17/Treg， inhibits the expression of Th17 cells， and promotes the expression of Treg cells in CIA mice， thereby exerting therapeutic effect on RA.

Application of individualized teaching based on the good-will preposing theory in the teaching of practical nursing students in the department of oncology / 中华医学教育探索杂志

Objective:To analyze the effectiveness of individualized teaching based on the good-will preposing theory in the teaching of practical nursing students in the department of oncology.Methods:Eighty practical nursing students who were accepted by the department of oncology from January 2019 to October 2020 were selected, and they were randomly divided into routine group and research group with 40 students in each group. The routine group was taught by conventional methods and the research group was taught by individualized teaching methods based on the good-will preposing theory, respectively. The scores of theory and practice assessment and the changes of willingness and confidence of practical nurses in the department of oncology before and after the teaching, and the satisfaction with the teaching mode were compared between the two groups. SPSS 25.0 was used for t test and rank sum test. Results:The scores of theoretical and practical assessment in the two groups after teaching were higher than those before teaching ( P<0.05), and the scores of theoretical and practical assessment in the study group were higher than those in the routine group ( P<0.05). There were statistically significant differences in the grade distribution of willingness and confidence to undertake the career of oncology between the two groups of practical nursing students after teaching compared with that before teaching ( P<0.05). In the study group, the satisfaction scores of meeting learning willingness, improving learning enthusiasm, improving teaching efficiency, and strengthening the interaction between teachers and students in study group were higher than those in routine group ( P<0.05). Conclusion:Application of individualized teaching based on the good-will preposing theory among practical nursing students in the department of oncology may improve assessment performance, enhance their willingness and confidence to undertake the career of oncology, and improve their teaching satisfaction.

The combination of EGCG with warfarin reduces deep vein thrombosis in rabbits through modulating HIF-1α and VEGF via the PI3K/AKT and ERK1/2 signaling pathways / 中国天然药物

Deep venous thrombosis (DVT) poses a major challenge to public health worldwide. Endothelial cell injury evokes inflammatory and oxidative responses that contribute to thrombus formation. Tea polyphenol (TP) in the form of epigallocatechin-3-gallate (EGCG) has anti-inflammatory and oxidative effect that may ameliorate DVT. However, the precise mechanism remains incompletely understood. The current study was designed to investigate the anti-DVT mechanism of EGCG in combination with warfarin (an oral anticoagulant). Rabbits were randomly divided into five groups. A DVT model of rats was established through ligation of the inferior vena cava (IVC) and left common iliac vein, and the animals were orally administered with EGCG, warfarin, or vehicle for seven days. In vitro studies included pretreatment of human umbilical vein endothelial cells (HUVECs) with different concentrations of EGCG for 2 h before exposure to hydrogen peroxide. Thrombus weight and length were examined. Histopathological changes were observed by hematoxylin-eosin staining. Blood samples were collected for detecting coagulation function, including thrombin and prothrombin times, activated partial thromboplastin time, and fibrinogen levels. Protein expression in thrombosed IVCs and HUVECs was evaluated by Western blot, immunohistochemical analysis, and/or immunofluorescence staining. RT-qPCR was used to determine the levels of AGTR-1 and VEGF mRNA in IVCs and HUVECs. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis and ROS generation was assessed by 2',7'-dichlorofluorescein diacetate reagent. In vitro and invivo studies showed that EGCG combined with warfarin significantly reduced thrombus weight and length, and apoptosis in HUVECs. Our findings indicated that the combination of EGCG and warfarin protects HUVECs from oxidative stress and prevents apoptosis. However, HIF-1α silencing weakened these effects, which indicated that HIF-1α may participate in DVT. Furthermore, HIF-1α silencing significantly up-regulated cell apoptosis and ROS generation, and enhanced VEGF expression and the activation of the PI3K/AKT and ERK1/2 signaling pathways. In conclusion, our results indicate that EGCG combined with warfarin modifies HIF-1α and VEGF to prevent DVT in rabbits through anti-inflammation via the PI3K/AKT and ERK1/2 signaling pathways.

Effect of Asiaticoside on Expression of Th17/Treg Cells in DBA/1 Mice with Collagen-Induced Arthritis / 中国实验方剂学杂志

ObjectiveTo observe the effect of asiaticoside （AC） on the expression of T helper 17 （Th17） cells and regulatory T （Treg） cells in DBA/1 mice with collagen-induced arthritis （CIA）. MethodMale SPF DBA/1 mice were randomized into six groups according to body weight： control group， CIA group， methotrexate group （MTX group， ip， 0.5 mg·kg-1）， and AC low-， medium-， and high-dose groups （ig， 5， 15， 45 mg·kg-1， respectively）. Modeling was performed in rats other than the control group. To be specific， they were immunized with bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and with bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21st day. Administration began on the day of the second immunization， once a day for 28 days. On the 49th day， related tissues were collected. Then， hematoxylin-eosin （HE） staining was performed to observe the pathological changes of the joints. Immunohistochemical method was used to detect the expression of interleukin-17 （IL-17） and forkhead box protein-3 （FoxP3）， the markers of Th17 and Treg cells， respectively， immunofluorescence double staining the expression of IL-17 and FoxP3 in CD4+T cells of mouse joint tissue， and flow cytometry the proportions of Th17 and Treg cells in mouse lymph nodes. ResultCompared with the control group， CIA group demonstrated joint disorder， damage of articular cartilage and bone， severe bone erosion （P<0.01）， increase in stained CD4 and IL-17 and the integral absorbance （IA） （P<0.01）， decrease in stained FoxP3 and the IA （P<0.01）， rise of Th17/Treg ratio （P<0.01）， elevation of Th17 expression in mouse lymph nodes （P<0.01）， and reduction in Treg expression （P<0.01）. Compared with CIA group， MTX group and three AC groups showed normal joints， alleviated bone erosion and damage， intact and smooth joint surface， and decrease in stained IL-17 and IA （P<0.05， P<0.01）， and MTX group and AC medium-dose and high-dose groups registered decrease in stained CD4 and IA （P<0.01） and reduction in Th17/Treg ratio （P<0.05， P<0.01）. Moreover， AC medium-dose and high-dose groups showed rise in stained FoxP3 and IA （P<0.05， P<0.01）. In the lymph nodes of mice， decrease in expression of Th17 cells （P<0.05， P<0.01） and the increase in expression of Treg cells （P<0.05， P<0.01） were observed in all the three AC group. ConclusionAC can regulate Th17/Treg balance by inhibiting the expression of Th17 cells and promoting the expression of Treg cells in CIA mice.

Exploring the mechanism of Buxue Yimu Pill on hemorrhagic anemia through molecular docking, network pharmacology and experimental validation / 中国天然药物

Buxue Yimu Pill (BYP) is a classic gynecological medicine in China, which is composed of Angelica sinensis (Oliv.) Diels, Leonurus japonicus Houtt, Astragalus membranaceus (Fisch.) Bunge, Colla corii asini and Citrus reticulata Blanco. It has been widely used in clinical therapy with the function of enriching Blood, nourishing Qi, and removing blood stasis. The current study was designed to determine the bioactive molecules and therapeutic mechanism of BYP against hemorrhagic anemia. Herein, GC-MS and UPLC/Q-TOF-MS/MS were employed to identify the chemical compounds from BYP. The genecards database (https: //www.genecards.org/) was used to obtain the potential target proteins related to hemorrhagic anemia. Autodock/Vina was adopted to evaluate the binding ability of protein receptors and chemical ligands. Gene ontology and KEGG pathway enrichment analysis were conducted using the ClusterProfiler. As a result, a total of 62 candidate molecules were identified and 152 targets related to hemorrhagic anemia were obtained. Furthermore, 34 active molecules and 140 targets were obtained through the virtual screening experiment. The data of molecular-target (M-T), target-pathway (T-P), and molecular-target-pathway (M-T-P) network suggested that 32 active molecules enhanced hematopoiesis and activated the immune system by regulating 57 important targets. Pharmacological experiments showed that BYP significantly increased the counts of RBC, HGB, and HCT, and significantly down-regulated the expression of EPO, IL-6, CSF3, NOS2, VEGFA, PDGFRB, and TGFB1. The results also showed that leonurine, leonuriside B, leosibiricin, ononin, rutin, astragaloside I, riligustilide and levistolide A, were the active molecules closely related to enriching Blood. In conclusion, based on molecular docking, network pharmacology and validation experiment results, the enriching blood effect of BYP on hemorrhagic anemia may be associated with hematopoiesis, anti-inflammation, and immunity enhancement.

Analysis of animal models of ulcerative colitis based on characteristics of clinical symptoms of traditional Chinese and Wes-tern medicine / 中国中药杂志

This article aims to provide a good experimental method for the study of drug treatment of ulcerative colitis. According to the characteristics of ulcerative colitis's clinical symptoms, common ulcerative colitis animal models were analyzed. Based on the characteristics of clinical symptoms of traditional Chinese medicine and Western medicine for ulcerative colitis disease, the existing commonly used animal models of ulcerative colitis were analyzed to summarize the current matching degree, advantages and disadvantages of the exi-sting animal models of ulcerative colitis and clinical symptoms. At present, studies on ulcerative colitis mainly adopt four types of induction modeling methods, such as immunization, chemical stimulation, compound method and gene model. There are many reported methods of colitis modeling, but no model can reflect the characteristics of clinical symptoms of ulcerative colitis treated with Western or Chinese medicine. This article summarizes the characteristics, clinically relevant symptoms and applicable scope of immunization, chemical stimulation, compound method, and gene model, so as to provide a reliable animal model for subsequent studies of prevention and treatment of colitis.

Anticoagulant therapy in elderly patients with nephrotic syndrome / 中华老年医学杂志

There is a high incidence of thromboembolic events in patients with nephrotic syndrome(NS), and the risk of thrombosis and bleeding increases in the elderly.On the basis of the guidelines of Kidney Disease: Improving Global Outcomes(KDIGO)glomerulonephritis 2020, the risk assessment of thromboembolism and bleeding, the timing of anticoagulant therapy and prevention and the selection of drugs for elderly NS individuals are discussed in this review.

Differentially expressed microRNAs in the testis of male rats exposed to cigarette smoke: Screening and function verification / 中华男科学杂志

Objective@#To screen differentially expressed miRNAs in the testis of male rats exposed to cigarette smoke (CS) and identify the early molecular markers of CS-induced apoptosis of testicular cells.@*METHODS@#We randomly divided 200 SPF male SD rats into blank control and low-dose (10 non-filter cigarettes/d), medium-dose (20 non-filter cigarettes/d) and high-dose (30 non-filter cigarettes/d) CS exposure groups. After 2, 4, 6, 8 and 12 weeks of CS exposure, we observed the histopathological changes of the testis by HE staining, detected the apoptosis of the testicular cells by TUNEL, and determined the expressions of caspase-3 and caspase-9 in the testis tissue by immunohistochemistry, RT-PCR and Western blot. Based on the laboratory results, we selected 4 testicular samples from the 12-week high-dose group and another 4 from the control for miRNA microarray-based screening, bioinformatics analysis, and verification of differentially expressed miRNAs in all the animals by RT-PCR.@*RESULTS@#Compared with the controls, the CS-exposed rats showed dose- and time-dependent increase in the atrophy of the testis and significantly increased number of apoptotic testis cells from the 6th week of exposure (P < 0.05), with dramatically up-regulated expressions of caspase-3 (P < 0.01) and caspase-9 protein and mRNA (P < 0.05) in the testis tissue. Microarray-based screening and RT-PCR revealed 5 differentially expressed miRNAs in the testis of the CS-exposed rats, of which miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 were down-regulated, and miR-155-5p up-regulated, and the target genes of the differentially expressed miRNAs positively regulated the apoptosis of the testicular cells.@*CONCLUSIONS@#The differentially expressed miRNAs miR-155-5p, miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 regulate CS-induced apoptosis of testicular cells, and may become biomarkers for early diagnosis and prognosis of CS-induced spermatogenesis obstruction.《.

Research on the mediation effect of expectation gap of postpartum support between perceived stress and postpartum depression / 中国实用护理杂志

Objective:To investigate the relationships of expectation gap of postpartum support with perceived stress and postpartum depression, and the mediating role of the former in the association between the latter two.Methods:A total of 278 convenient sample of puerperas at 6-8 weeks after delivery from June to August in 2019 in Shenzhen Hospital of Southern Medical University were investigated with the Perceived Stress Scale, the Chinese version of the Postpartum Social Support Questionnaire, and the Edinburgh Postnatal Depression Scale. Structure equation model was established and Bootstrap method was used to explore the direct and indirect effects of these variables.Results:The perceived stress score, and expectation gap of postpartum support score were (26.50±2.50), (25.30±5.79), respectively; and the postpartum depression score was (14.60±2.10). The incidence of postpartum depression(defined as postpartum depression score ≥10) was 37.4%(104/278). Path analysis showed that the model was well fitted (χ 2/ df was 0.265, Tucker-Lewis index was 1.0, comparative fit index was 1.0,root mean square of approximate error was 0, root mean square of standard deviation and residual error was 0.04). Perceived stress positively correlated with expectation gap of postpartum support, and postpartum depression ( P<0.05). Expectation gap of postpartum support positively correlated with postpartum depression ( P<0.05). The effect of perceived stress on postpartum depression was partially mediated by expectation gap of postpartum support (Estimate was 0.285, 95% CI 0.197-0.352). Conclusions:Perceived stress had direct or indirect effect via expectation gap of postpartum support on postpartum depression. This indicated that the medical staff can build a comprehensive support system, reduce the experience of perceived stress among puerperas, improve social support satisfaction, and thus reduce the incidence of postpartum depression.

Effect of Fangji Huangqitang on Function of Human Umbilical Vein Endothelial Cells / 中国实验方剂学杂志

Objective:To study the effects of Fangji Huangqitang（FJHQT） on migration， adhesion，invasion and tube formation of human umbilical vein endothelial cells （HUVECs） induced by vascular endothelial growth factor （VEGF）. Method:HUVECs were induced by VEGF （20 μg·L^-1） <italic>in vitro</italic>. The effects of FJHQT （0.25，0.5，1 g·L^-1） on HUVECs were detected by methyl thiazolyl tetrazolium（MTT）， scratch repair， transwell migration， adhesion， invasion and tube formation. Protein in HUVECs was extracted and protein expression levels of phosphorylated Janus kinase 1 （p-JAK1） were detected by Western blot. Result:Compared with control group， VEGF （20 μg·L^-1） can increase the proliferation， scratch repair， transwell migration， adhesion， invasion and tube formation of HUVECs cells （<italic>P</italic><0.01）， compared with VEGF group， FJHQT （0.25，0.5，1 g·L^-1） ，there is no significant effect on the proliferation of HUVECs induced by VEGF for 24 hours， but it can significantly reduce the scratch repair， migration， adhesion， invasion and tube formation of HUVECs induced by VEGF within 24 hours （<italic>P</italic><0.05）. Compared with blank group， VEGF could induce abnormal elevation of p-JAK1 in HUVECs （<italic>P</italic><0.01）， while FJHQT （0.25，0.5，1 g·L^-1） could significantly reduce the expression levels of p-JAK1 （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:FJHQT can inhibit the migration， adhesion and invasion of HUVECs， the mechanism may be related to JAK1.

Effect of Fangji Huangqitang on DBA/1 Mice Collagen Induced Arthritis and Synovial Angiogenesis / 中国实验方剂学杂志

Objective:To observe the effect of Fangji Huangqitang （FJHQT） on collagen induced arthritis （CIA） and synovial angiogenesis in DBA/1 mice. Method:DBA/1 mice were randomly divided into normal group， CIA group and FJHQT group. DBA/1 mice in CIA group and FJHQT group were immunized with bovine type Ⅱ collagen and complete Freund's adjuvant on the first day， and DBA/1 mice were immunized with bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21^st day to establish CIA model. On the day of the second immunization， the drug was given by gavage once a day for 28 days. On the 22^nd day， the arthritis score and other symptoms of CIA mice were observed. On the 49^th day， Hematoxylin eosin （HE） staining was carried out to observe the angiogenesis in the synovium of CIA mice， the expression of vascular endothelial cell marker platelet endothelial cell adhesion molecule-1 （CD31） and vascular endothelial growth factor （VEGF） in the synovium of CIA mice were detected. Immunofluorescence double staining was used to detect the mature and immature vessels in the synovium of CIA mice. And the microvascular growth of the rat thoracic aortic ring was induced by VEGF （20 μg·L^-1）. The effects of FJHQT （0.25， 0.5， 1 g·L^-1） at different concentrations were observed under microscope. Result:Compared with the normal group， the inflammation， joints， red and swelling of the inflammatory joints of the CIA group were significantly increased （<italic>P</italic><0.01）. The scores of clinical arthritis， the incidence rate， synovial inflammation and angiogenesis were significantly increased （<italic>P</italic><0.01）. The density of blood vessels， the positive expression of CD31 and VEGF， the number of immature vessels in synovial membrane were significantly increased （<italic>P</italic><0.01）. And compared with the CIA group， the inflammation， joint swelling， and malformation of the FJHQT group were significantly improved， the clinical arthritis score， incidence rate， synovial inflammation and angiogenesis were significantly reduced （<italic>P</italic><0.01）. The vascular density， the positive expression of CD31 and VEGF， and the number of immature blood vessels in synovial membrane were significantly increased （<italic>P</italic><0.01）. Compared with blank group， VEGF could significantly induce the growth of microvasculature in rat thoracic aortic ring （<italic>P</italic><0.01）. Compared with VEGF group， FJHQT（0.25， 0.5， 1 g·L^-1） could significantly inhibit the formation of microvasculature in rat thoracic aortic ring （<italic>P</italic><0.01）. Conclusion:FJHQT can effectively alleviate the clinical symptoms and condition of CIA mice， reduce the clinical arthritis score and incidence rate，and inhibit the synovial angiogenesis of CIA mice joints and VEGF induced microvascular formation in rat thoracic aortic rings.

Progress in application of Bletilla striata polysaccharide in novel drug delivery systems and biomaterials / 中国中药杂志

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.

Long-term effect of biological anti-rheumatic drugs on ankylosing spondylitis / 中华风湿病学杂志

Objective:To study the efficacy and drug-related adverse reactions of long-term appli-cation of biological anti-rheumatic drugs (bDMARDs) to patients with ankylosing spondylitis (AS), and provide reference for clinical diagnosis and treatment.Methods:We retrospectively analyzed the clinical data of AS patients who were followed-up for more than 5 years in the Department of Rheumatology and Immunology of Peking University Shenzhen Hospital. The patients treated with bDMARDs alone or combined with traditional antirheumatic drugs were included as the treatment group, while those who did not receive biological or non-biological antirheumatic therapy were included as the control group. The data collected included clinical sym-ptoms, inflammatory biomarkers, imaging results, drug applications and drug-related adverse reactions, etc. The counting data were tested by χ2 test, the measurement data in normal distribution was tested by t test, and the measurement data that not normally distributed was tested by Mann-Whitney U test. Paired test was used for statistical processing before and after treatment. Results:We collected the data of 114 eligible patients, including 64 in the treatment group and 50 in the control group. There were no significant differences in baseline data between the 2 groups, including mean follow-up time, course of disease, age, sex ratio, HLA-B27 positive rate, morning stiffness duration, night pain, peripheral arthritis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and imaging. After 5 years, patients in the treatment group had shorter morning stiffness [(3±7) min vs (26±37) min, t=4.827, P<0.01], lower nighttime pain rates [(3/64, 4.8%) vs (29/50,58.0%), χ2=38.329, P<0.01], lower ESR level [(14±14) mm/1 h vs (20±18) mm/1 h, t=2.102, P=0.038], lower CRP level [(7±8) mg/L vs (14±19) mg/L, t=2.431, P=0.017], and lower progression rate of sacroiliac arthritis [(18/64, 28.1%) vs (35/50, 70.0%), χ2=19.786, P<0.01], than the control group. The main drug-related adverse reactions in the treatment groupincluded reversible leucopenia, elevated transaminase level, redness and swelling at the injection site. Conclusion:Biologics treatment for more than 3 consecutive years can effectively control the clinical symptoms of most AS patients, reduce inflammatory indicators and delay the imaging progression of the sacroiliac joint. Without treatment, the imaging progress of the sacroiliac joint in AS patients could be 70% after 5 years.

Immunotherapy with PD-1 and PD-L1 inhibitors for prostate cancer / 中华男科学杂志

Prostate cancer (PCa) has become one of the common malignant diseases in elderly men, and its incidence is increasing year by year. Apart from surgery, radiotherapy and chemotherapy, immunotherapy, as with the programmed death receptor-1 (PD-1) or the programmed death ligand-1 (PD-L1) inhibitor, is a most promising new strategy for the treatment of PCa. PD-1 and PD-L1 inhibitors restore the activity of T cells by blocking the PD-1/PD-L1 signaling pathway in tumor cells, reverse the mechanism of tumor immune escape, recover the immune system and directly kill tumor cells. This review focuses on the current progress in the studies of PD-1 and PD-L1 inhibitors in the treatment of PCa.

Effect of traditional anti-rheumatic drugs on ankylosing spondylitis: 10 years clinical observation / 中华风湿病学杂志

Objective:To observe the long-term effects of conventional disease modifying anti-rheumatic drugs (cDMARDs) in the treatment of ankylosing spondylitis (AS) and drug-related adverse reactions, and provide reference to clinical treatment and assessment.Methods:Retrospective analysis was performed for AS patients with more than 10 years follow-up records in the Department of Rheumatology and Immunology, Peking University Shenzhen Hospital. The AS patients enrolled were treated with cDMARDs, non-steroid anti-inflammatory Drugs (NSAIDs), and glucocorticoidsonl only. The treatment group was treated continuously for at least 3 years, and the control group was untreated or treated for less than 3 months. Clinical symptoms, inflammatory indicators, imaging results and drug-related adverse reactions of all patients were collected for statistical analysis. The counting data were tested by χ2 test, the measurement data in normal distribution was tested by t test, and the measurement data that not normally distributed was tested by mann-whitney U test. Paired test was used for statistical processing before and after treatment. Results:A total of 166 eligible patients were included, including 111 in the treatment group and 55 in the control group. There were no statistical significant differences between the treatment group and the control group at baseline including the mean follow-up time, symptomatic disease course, age, sex ratio, human lymphocyte antigen (HLA)-B27 positive rate, duration of morning stiffness, pain at night, peripheral arthritis, ESR, CRP and imaging data. After 10 years, the treat-ment group had shorter morning stiffness[(8±18) vs (22±34), U=2 228, P=0.008], less nocturnal pain [(2/1.9%) vs (19/36.5%), χ2=37.037, P<0.01], lower ESR level [(14±13) vs (20±19), t=2.249, P=0.026], lower CRP level [(6±6) vs (10±11), t=2.154, P=0.033], lower incidence of peripheral arthritis [(23/20.7%) vs(25/45.5%), χ2=10.946, P=0.001] and lower sacroiliac arthritis progression rate [(28/25.2% ) vs (46/83.6%), χ2=50.922, P<0.01], and lower spinal progression rate [(8/7.2%) vs (51/92.7%), χ2=117.407, P<0.01] compared with the control group. The differences between the two groups was statistically significant. The main medications and drug proportions in the treatment group were as follows: sulfasalazine (100%), methotrexate (86.5%), NSAIDs (98.2%), glucocorticoid (78.4%) and thalidomide (62.2%). The main drug-related adverse reactions that occurred during the treatment included dizziness, abnormal menstruation, and reversible liver dysfunction. Conclusion:The combination of cDMARDs can effectively control the clinical symptoms of most AS patients, reduce inflammation indicators, delay the progression of sacroiliac joint and spinal damage, and have no serious drug-related adverse reactions. Almost all of the untreated AS patients have radiographic progression of the sacroiliac joint and spine.

Effect of hysteroscopic adhesion separation combined with Folly urinary catheter placement in the treatment of hysterectomy / 中国综合临床

Objective:To investigate the application of Folly urethral catheter in transvastatal resection of adhesion (TCRA) and its preventive effect on prevention of re-adhesion.Methods:A total of 78 patients with intrauterine adhesions admitted to the Department of gynecology and obstetrics of the Maternal and Child Health Care Hospital Affiliated to Anhui Medical University from March 2018 to March 2019 were selected as the study objects.The prospective study was conducted and divided into two groups according to the computer random number method.In the control group, 39 cases were treated by TCRA combined with intrauterine placement of contraceptive ring, while in the observation group, 39 cases were treated by hysteroscopic adhesion separation operation combined with Folly catheter placement.The curative effect, intrauterine adhesions, menstrual improvement score, recurrence and pregnancy were compared before and 6 months after operation.Results:The total effective rate of the observation group was 94.87% (37/39), and that of the control group was 79.49% (31/39), The difference between the two groups was statistically significant (χ 2=4.129, P<0.05). The score of intrauterine adhesions was (22.14±2.57) in the control group and (1.76±0.87) in the observation group, and (23.05±3.08), (1.81±0.60) in the observation group, there was no significant difference between the two groups( t=1.417, 0.295; all P>0.05). At 3 months after operation, the scores of intrauterine adhesions and menstrual states in the control group were (17.63±2.88) and (1.07±0.38), respectively, and those in the observation group were (14.27±3.52) and (0.53±0.21), the difference between the two groups was statistically significant( t=4.614, 7.767, all P<0.001). There were significant differences in the scores of intrauterine adhesions and menstrual state before and after operation in the observation group ( t=7.297, 4.539, all P<0.001). There were significant differences in the scores of intrauterine adhesions and menstrual states before and after operation in the observation group ( t=11.723, 12.575, all P<0.001). The recurrence rate was 23.08% (9/39) in the observation group and 46.15% (18/39) in the control group at 6 months after operation.The difference was statistically significant ( P=0.032). The pregnancy rate of the observation group was observed.12.82% (5/39), 7.69% (3/39) in the control group, the difference was not statistically significant( P=0.455). Conclusion:Hysteroscopic adhesion separation combined with Folly catheter placement for the treatment of intrauterine adhesions can significantly improve the short-term efficacy, prevent re-adhesion, and better regulate the menstrual cycle.

Protective effects of reduced glutathione on renal toxicity induced by vancomycin in critically ill patients / 中华危重病急救医学

Objective:To observe the changes of renal function in critically ill patients after using vancomycin and analyze the renal protective effect of reduced glutathione (GSH) on vancomycin nephrotoxicity.Methods:The clinical data of patients with severe infection who were administered with vancomycin or plus infusion of GSH admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019 were collected during the study period, and the patients were divided into only vancomycin group and vancomycin combined with GSH group. The gender, age, body weight, underlying diseases, clinical diagnosis, severity score, renal function before and after taking the medicine, average daily dose and treatment duration of vancomycin and GSH, length of ICU stay and clinical outcomes were recorded and analyzed.Results:A total of 217 patients were enrolled, with 127 patients in the only vancomycin group, and 90 in the combination with GSH group. There was no statistically significant difference between the two groups in terms of gender, body weight, duration of vancomycin treatment, history of chronic kidney disease, and ICU mortality. The main causes of 217 patients admitted to the ICU were lung infection, sepsis/septic shock, and severe acute pancreatitis (SAP) and so on. The majority of patients in only vancomycin group had lung infections (63.0%), while the main etiology in combination with GSH group was SAP (46.7%). Compared with the only vancomycin group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score in the combination with GSH group significantly decreased [15.0 (10.5, 21.0) vs. 27.0 (20.0, 31.0), P < 0.01], but the quick sequential organ failure assessment (qSOFA) score was significantly higher [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], the basic renal function was poorer [serum creatinine (SCr, μmol/L): 102.0 (64.7, 178.0) vs. 56.0 (42.0, 71.0), blood urea nitrogen (BUN, mmol/L): 11.5 (6.7, 18.4) vs. 4.70 (3.5, 8.1), both P < 0.05], and the average daily dose of vancomycin was lower (mg·kg -1·d -1: 22.22±10.09 vs. 25.51±9.56, P < 0.05). The renal function of patients was getting worse significantly after vancomycin usage as compared with before [SCr (μmol/L): 68.0 (50.3, 103.4) vs. 56.0 (42.0, 71.0), BUN (mmol/L): 5.4 (3.6, 9.6) vs. 4.7 (3.5, 8.1), both P < 0.05]. However, the renal function indexes of the combination with GSH group were better than those before treatment [SCr (μmol/L): 81.0 (61.0, 129.0) vs. 102.0 (64.7, 178.0), P < 0.05; BUN (mmol/L): 8.4 (6.2, 17.8) vs. 11.5 (6.7, 18.4), P > 0.05], and the length of ICU stay was significantly shorter than that in the only vancomycin group [days: 29.0 (14.0, 54.2) vs. 37.0 (25.0, 55.0), P < 0.05]. Conclusions:The incidence of drug-induced renal injury caused by vancomycin is high. The GSH can significantly reduce their renal toxicity and shorten the length of hospital stay.

High dose vitamin C significantly reduces the nephrotoxicity of vancomycin in critically ill patients / 中华危重病急救医学

Objective:To observe the changes of renal function in critically ill patients using vancomycin and analyze the renal protective effect of high dose vitamin C (VC) on vancomycin nephrotoxicity.Methods:Retrospective analysis was carried out to enroll the patients who were hospitalized in emergency intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019. All patients were administered with vancomycin or VC infusion in addition. According to the infusion of vancomycin alone or in combination with VC, the patients were divided into vancomycin group and vancomycin in combination with VC group; vancomycin group was further divided into two groups according to before vancomycin or after vancomycin usage; combination group were further divided into two groups according to before VC use or after VC. The initial dosage of vancomycin was calculated according to the actual weight of the patient and adjusted according to the renal function. The dosage of VC was determined according to the disease severity of the patient, and the dosage range was 50-200 mg·kg -1·d -1, continuously infused into the body. The age, gender, weight and renal function etc. were recorded and analyzed. Results:A total of 245 patients who met the requirements were included in the analysis. There were 127 patients in the vancomycin group and 118 patients in the combination group. The causes of patients admitted to ICU were pulmonary infection, sepsis, severe acute pancreatitis, etc. Among them, pulmonary infection accounted for 63.0% in vancomycin group, while severe acute pancreatitis accounted for 61.9% in combination group. The quick sequential organ failure assessment (qSOFA) score of combination group was significantly higher than that of vancomycin group [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], its basic renal function was also significantly worse [serum creatinine (SCr, μmol/L): 98.0 (65.0, 178.2) vs. 56.0 (42.2, 71.0), blood urea nitrogen (BUN, mmol/L): 11.30 (6.48, 18.38) vs. 4.70 (3.45, 8.10), both P < 0.05], and the average daily dose of vancomycin was also significantly lower than that of vancomycin group (mg·kg -1·d -1: 23.0±9.4 vs. 26.6±8.5, P < 0.01). Compared with vancomycin before administration, the renal function was getting worse significantly after vancomycin administration [SCr (μmol/L): 68.0 (50.2, 104.5) vs. 56.0 (42.2, 71.0), BUN (mmol/L): 5.35 (3.75, 9.83) vs. 4.70 (3.45, 8.10), both P < 0.05]. Combination with VC significantly improved renal function compared with that before VC treatment [SCr (μmol/L): 79.0 (58.0, 129.0) vs. 98.0 (65.0, 178.2), P < 0.05; BUN (mmol/L): 9.60 (6.10, 18.30) vs. 11.30 (6.48, 18.38), P > 0.05] and shortened the length of ICU stay [days: 28.5 (14.8, 54.2) vs. 37.0 (25.0, 55.0), P < 0.01]. Conclusions:The incidence of drug-induced renal injury caused by vancomycin is high. Intravenous high dose VC can significantly reduce the nephrotoxicity of vancomycin and shorten the length of hospital stay. When vancomycin is used in critically ill patients, VC can be used in combination to reduce or avoid drug-induced renal injury, improve curative effect and reduce toxic effects.

Study on the optimization of administration regimen of vancomycin in critical patients / 中华危重病急救医学

Objective:To observe the changing characteristics of pharmacokinetic and pharmacodynamic (PK-PD) parameters of vancomycin in critical patients under different drug regimens and to further explore the influencing factors.Methods:The clinical data of patients who treated with vancomycin and recorded by steady-state through concentration (C min) admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to December 2018 were analyzed retrospectively. The patients were divided into three groups according to the dosing interval (groups of q12 h, q8 h and q6 h respectively) and C min was collected. The serum concentration of vancomycin before (0 hour) and 1, 2, 4, 6, 8, 12 and 24 hours after administration were estimated by JPKD Ver 3.1. Area under the curve (AUC 0-24 h) was estimated by trapezoidal area method. Minimum inhibitory concentration (MIC) of pathogenic microorganisms in the same period was retrieved, thus AUC 0-24 h/MIC was calculated. Results:285 patients with 529 records of C min were enrolled in the study, including 375 data in q12 h group, 121 data in q8 h group and 33 data in q6 h group. After unifying daily dose by JPKD Ver 3.1, the C min (10-20 mg/L) reaching rate of q12 h group, q8 h group, q6 h group were 35.7%, 43.8% and 60.6%, respectively, while only q12 h group was statistically significant compared with q6 h group ( P < 0.01). q6 h group and q8 h group showed higher C min than q12 h group (mg/L: 13.8±5.2, 13.5±7.3 vs. 11.4±7.9, both P < 0.05) and lower peak concentration (C max) than q12 h group (mg/L: 19.4±5.3, 21.5±7.3 vs. 23.9±8.1, both P < 0.05). However, there was no significant difference in terms of percentage of PD target (AUC 0-24 h/MIC≥400) among the three groups (q12 h group, q8 h group, q6 h group were 38.1%, 41.3%, 45.5%, P > 0.05). Multiple linear regression analysis showed that creatinine clearance (CCr) and vancomycin clearance (CLvancomycin) were the main influencing factors of vancomycin PD parameters such as C min and AUC 0-24 h/MIC ( r values of CCr were -0.391, -0.424, and rvalues of CLvancomycin were -0.673, -0.663, all P < 0.01), and were negatively correlated with age ( r values were -0.432 and -0.488, respectively, both P < 0.01). Conclusions:At the same daily dose, C min can be increased and C max can be decreased by increasing the frequency of vancomycin administration, thus minimize the fluctuation of vancomycin serum concentration, but AUC 0-24 h/MIC is not affected. Vancomycin administration regimen in severe patients should be optimized according to CCr, CLvancomycin and age.

Exploring Anti-inflammation Mechanism of Pien Tze Huang via Regulating of Microglia Polarization / 中国实验方剂学杂志

Objective::To investigate the anti-inflammation mechanism of Pien Tze Huang (PTH) via regulating microglia polarization. Method::The experiment was divided into five groups, Blank, M1[lipopolysaccharide (LPS) 100 μg·L-1+ interferon-γ(IFN-γ) 10 μg·L-1], M1-PTH group[LPS 100 μg·L-1+ IFN-γ 10 μg·L-1+ PTH 0.4 g·kg-1], M2 group[interleukin-4 (IL-4) 20 μg·L-1], and M2-PTH group[IL-4 20 μg·L-1+ PTH 0.4 g·kg-1]. The concentration of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and transforming growth factor-β1(TGF-β1) in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA), the levels of inducible nitric oxide synthase(iNOS) and arginine-1 (Arg-1) mRNA were detected by real-time fluorescent quantitative polymerase chain reaction technique(Real-time PCR), and the expression levels of p-STAT1, p-STAT3, iNOS, p-STAT6, and Arg-1 were detected by Western blot. Result::The concentration of NO and TNF-α of the culture supernatant, the level of iNOS mRNA, as well as the level of p-STAT1, p-STAT3 and iNOS in M1 group, which were significantly increased(P<0.01) .Compared with blank group, but the concentration of NO and TNF-α were down-regulated(P<0.01), and iNOS mRNA(P<0.05), as well as the expression of iNOS, p-STAT1, and p-STAT3 was decreased (P<0.05, P<0.01) after the invention of PTH in M1-PTH group compared with M1 group. The concentration of IL-10 and TGF-β1 in the culture supernatant, the mRNA level of Arg-1, as well as the levels of p-STAT6 and Arg-1 were significantly increased in M2 group when compared with Blank group, addition to the concentration of IL-10 and TGF-β1 were up-regulated(P<0.05, P<0.01), and the expression of Arg-1 mRNA, the level of Arg-1, p-STAT6 were enhanced(P<0.05, P<0.01) in M2-PTH group compared with M2 group. Conclusion::PTH plays an anti-inflammatory role via regulating microglia polarization.