Chemical composition of Boenninghausenia sessilicarpa / 中国药科大学学报

@#The petroleum ether fraction of ethanol extracts from Boenninghausenia sessilicarpawas isolated by combination of several chromatographic methods including silica gel, ODS, and Sephadex LH-20 column chromatography, and finally purified by preparative HPLC. The structures of the isolated compounds were identified based on the spectral data. As a result, 15 coumarin compounds were isolated and identified from the petroleum ether extraction. Their structures were determined as osthenon (1), murrangatin (2), 3-(1,1-dimethylallyl)-8-hydroxy-7-methoxycoumarin (3), xanthotoxin (4), isopimpinellin (5), chalepensin (6), isodemethylfuropinarine (7), imperatorin (8), phellopterin (9), heraclenol (10), byakangelicin (11), neobyakangelicol (12), chalepin (13), luvangetin (14), 3-(1, 1-dimethylallyl)-xanthyletin (15). Among them, compounds 1 - 3, 6 - 10 and 14 -15 were firstly isolated from B. sessilicarpa.

Mechanism of nuclear protein 1 in the resistance to axitinib in clear cell renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients.@*METHODS@#By exploring the half maximum inhibitory concentration (IC50) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance.@*RESULTS@#Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC50 were significantly higher than those of the sensitive cell lines (10.99 μmol/L, P < 0.01; 11.96 μmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 μmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib.@*CONCLUSION@#ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.

Effect of fluoxetine combined with Shugan Jieyu capsule in the treatment of patients with depression and its impact on heart rate variability / 四川精神卫生

BackgroundDepression is a kind of disease with relatively high suicide risk， which seriously affects the quality of life of patients and their families， and brings a great burden to society. Antidepressants in western medicine are effective， but the improvement of depressive symptoms is relatively limited by single use， and the combination of two antidepressants may increase the risk of adverse reactions in patients. The rational use of Chinese patent medicine and western medicine may play a complementary role， and the safety of Chinese patent medicine is high. ObjectiveTo explore the early clinical efficacy of fluoxetine combined with Shugan Jieyu capsule in the treatment of depression， and to compare the differences in efficacy， safety and influence on heart rate variability between fluoxetine combined with Shugan Jieyu capsule and fluoxetine alone， so as to provide references for clinical medication of depression patients. MethodsFrom December 2015 to June 2016， 64 patients who met the diagnostic criteria of depression in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） who were hospitalized in the Second Affiliated Hospital of Xinxiang Medical University were selected as the research objects， and were randomly divided into the combined medication group and the fluoxetine group with 32 patients in each group. Patients in both groups were treated with fluoxetine， while patients in the combined medication group were treated with Shugan Jieyu capsule on this basis. Patients in both groups were assessed with Hamilton Depression Scale-24 item （HAMD-24）， Hamilton Anxiety Scale （HAMA） and Heart Rate Variability （HRV） before treatment， and were assessed with HAMD-24 and Treatment Emergent Symptom Scale （TESS） at the end of the 2nd， 4th and 6th week of treatment， and HRV was analyzed again at the end of the 6th week of treatment. ResultsThe study ultimately included 60 patients with depression， with 30 cases in the combination therapy group and 30 cases in the fluoxetine group. At the end of the 2nd， 4th and 6th week of treatment， the HAMD-24 score of the combined drug group was lower than that of the fluoxetine group （t=-2.677， -3.960， -4.432， P<0.05 or 0.01）. Compared with before treatment， the 24-hour mean standard deviation of normal RR intervals （SDNN）， normal low frequency （nLF） and normal high frequency （nHF） in the combined treatment group were higher at the end of the 6th week （t=-73.970， -31.878， -38.721， P<0.01）， but significant lower in LF/HF （t=3.525， P<0.01）. At the end of the 6th week of treatment， the total effective rate of the combined treatment group was higher than that of fluoxetine group， and the difference was statistically significant （86.67% vs. 70.00%， χ2=18.764， P<0.01）. At the 2nd， 4th and 6th week of treatment， there was no significant difference in the number of adverse reactions between the two groups （P>0.05）. ConclusionCompared with fluoxetine alone， Shugan Jieyu capsule combined with fluoxetine may be better in clinical efficacy and improvement of heart rate variability in patients with depression， without increasing adverse reactions.

Clinical molecular diagnosis of breast and female reproductive system tumors / 中华检验医学杂志

The gynecological tumours such as Breast cancer or female reproductive system tumors are a serious threat to female health. With the development of molecular diagnosis, the genomic changes of gynecological tumours have been revealed continuously, and the diagnosis and treatment modes of tumors have gradually changed. The detection of molecular targets which potentially participated in the transformation or progress of disease has become an important section of the management of female reproductive tumors, and accurate identification of molecular targets of tumors plays an important role in disease diagnosis, monitoring of metastasis, prediction of recurrence and treatment. This review briefly discusses the risk assessment, molecular typing, targeted therapy, toxic and side effects, and prognosis evaluation of breast and female reproductive system tumors by molecular diagnosis.

Status quo and influencing factors of medication compliance in young newly diagnosed pulmonary tuberculosis patients / 中国实用护理杂志

Objective:To investigate the medication adherence and its influencing factors in young newly diagnosed pulmonary tuberculosis patients during different treatment periods, in order to provide a theoretical basis for formulating precise medication management strategies and thus improving the treatment success rate.Methods:A cross-sectional survey was conducted using a stratified random sampling method to select 283 young newly diagnosed pulmonary tuberculosis patients who visited and registered in the Kashgar region of Xinjiang from September 2021 to February 2022. The patients were divided into three groups according to the treatment time of receiving standard chemotherapy regimen: A (1-2 months of medication), B (3-4 months of medication), and C (5-6 months of medication), with 77, 89, and 117 cases, respectively. The clinical data of tuberculosis patients were collected by using the general information questionnaire,Eight-Item Morisky Medication Adherence Scale and Tuberculosis Medication Adherence Scale for tuberculosis patients.Results:Those who take medication well of three groups of young newly treated pulmonary tuberculosis patients were 93.5% (72/77), 89.9% (80/89), and 82.1% (96/117), respectively. The difference among the three groups was statistically significant ( χ2=6.23, P<0.05). Logistic regression analysis showed that social support was an influential factor for the 1st to 2nd month of medication ( OR=0.536, P<0.05); treatment confidence and psychological status were influential factors for the 3rd to 4th month of medication ( OR=0.668, 2.212, both P<0.05); comorbidity, social support, psychological status, and coping style were influential factors for the 5th to 6th month of medication ( OR values were 0.428 - 9.518, all P<0.05). Conclusions:The relevant factors that affect medication adherence vary among young newly diagnosed pulmonary tuberculosis patients at different stages of treatment. Accurate medication management strategies should be developed based on the influencing factors at each stage.

A pilot study of gray matter volume and function changes in patients after cardiopulmonary resuscitation / 中华急诊医学杂志

Objective:To explore the structural and functional alterations of related brain regions in patients after cardiopulmonary resuscitation (CPR) by brain magnetic resonance imaging (MRI).Methods:A single-center, observational, cross-sectional study design was used. Patients who had brain MRI scans during hospitalization between July 2020 and July 2021 in Emergency Department of the First Affiliated Hospital of Nanjing Medical University and had good neurologic outcomes were consecutive enrolled in this study. The healthy control (HC) group consisted of age- and sex-matched volunteers. The demographic and clinical data were recorded. The modified Rankin Scale (mRS) was used to check the recovery and degree of continued disabilities when patients performed MRI. Montreal cognitive assessment (MoCA) was used to assess cognitive functions. The analyses of voxel-based morphometry (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) were conducted. After data preprocessing, comparison of gray matter volume (GMV) and fALFF values between the case group and HC group were carried out, and the information of different brain regions was obtained. Partial correlation analyses were performed to evaluate the correlation between the image parameters of different clusters and clinical parameters.Results:Totally 13 patients were enrolled in this study and 13 were in the HC group. All patients achieved good neurologic outcome; mRS was 3 in 1 case, 2 in 3 cases, and 1 in 5 cases during MEI examination. The case group showed significantly lower MoCA score compared with the HC group ( P<0.001). There were significantly decreased GMVs in the right inferior frontal gyrus, superior temporal gyrus, left superior temporal gyrus, and transverse temporal gyrus in the case group. The patients showed significantly decreased fALFF values in the left postcentral gyrus and precentral gyrus, while increased fALFF values in the right putamen than the HC group (voxel-level P<0.001 and cluster-level P<0.05 with GRF correction). In addition, mean fALFF value in the right putamen was negatively correlated with MoCA score in the case group ( r=-0.710, P=0.021). Conclusions:Patients after CPR may have GMVs and neuronal spontaneous activity changes in some brain regions, and VBM and fALFF methods can be used to objectively evaluate the impaired brain functional activity in patients after successful CPR.

Clinical efficacy and anti-inflammation/anti-fibrosis effect of tripterygium glycosides in the treatment of diabetic nephropathy / 中国临床药理学与治疗学

AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ

A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression / 中华医学杂志(英文版)

BACKGROUND@#In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.@*METHODS@#Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors.@*RESULTS@#In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%.@*CONCLUSION@#Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.@*REGISTRITATION@#ChiCTR.org.cn, ChiCTR2100046766.

Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

Research advances on the mechanism of Wnt/β-catenin signaling pathway in body surface wound healing / 中华烧伤杂志

Wound healing is a slow and complex biological process, including inflammatory reaction, cell proliferation, cell differentiation, cell migration, angiogenesis, extracellular matrix deposition, tissue remodeling, and so on. Wnt signaling pathway can be divided into classical pathway and non-classical pathway. Wnt classical pathway, also known as Wnt/β-catenin signaling pathway, plays an important role in cell differentiation, cell migration, and maintenance of tissue homeostasis. Many inflammatory factors and growth factors are involved in the upstream regulation of this pathway. The activation of Wnt/β-catenin signaling pathway plays an important role in the occurrence, development, regeneration, repair and related treatment of skin wounds. This article review the relationship between Wnt/β-catenin signaling pathway and wound healing, meanwhile summarizes its effects on important processes of wound healing, such as inflammation, cell proliferation, angiogenesis, hair follicle regeneration, and skin fibrosis, as well as the role of inhibitors of Wnt signaling pathway in wound healing.

Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation / 中国中药杂志

This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1β, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1β, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.

Development and application syndromic surveillance and early warning system in border area in Yunnan Province / 中华流行病学杂志

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.

Analysis of the risk factors for poor prognosis and recurrence in patients with anti-NMDAR encephalitis / 中华预防医学杂志

To investigate the risk factors of poor prognosis and recurrence in patients with anti-NMDAR encephalitis. A single center, observational cohort study was used to retrospectively analyze 44 patients with anti NMDAR encephalitis hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from January 2014 to October 2020. The results showed that the interval from onset to immunotherapy in the poor prognosis group was significantly longer than that in the good prognosis group (t=2.045,P=0.047), and the course of disease in the poor prognosis group was significantly longer than that in the good prognosis group (t=4.127,P=0.000 2). The number of patients with clinical manifestations of dyskinesia was significantly increased (Fisher exact test: P=0.014). The patients with abnormal brain MRI in the poor prognosis group were significantly more than those in the good prognosis group (Fisher exact test: P=0.017), and the patients with slow wave>50% in the poor prognosis group were significantly more than those with slow wave <50% (Fisher exact test: P<0.001). Patients with the first onset of immunotherapy time <3 months, long course of disease, high intracranial pressure, and high cerebrospinal fluid protein are prone to relapse. Bivariate logistic regression analysis showed that patients with dyskinesia, abnormal brain MRI, and slow wave EEG more than 50% were risk factors for poor prognosis (OR values were 4.687, 4.978, and 24.500, respectively; P values were 0.018, 0.016, and 0.000, respectively). The time of first-line immunotherapy for the first onset<3 months was the risk factor for recurrence (OR 17.231, P=0.010). In conclusion, dyskinesia, abnormal brain MRI and slow wave of EEG more than 50% may be the risk factors for poor prognosis of patients. The duration of immunotherapy less than 3 months after the first onset might be the risk factor for recurrence.

Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma / 中西医结合学报

OBJECTIVE@#Although there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.@*METHODS@#Small interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.@*RESULTS@#JAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.@*CONCLUSION@#JAML is a novel target for kaempferol against LUAD cells. Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268-276.

Integrating magnetization transfer imaging and fat suppression T 2WI for predicting the clinical activity of Graves ophthalmopathy / 中华放射学杂志

Objective:To investigate the value of magnetization transfer imaging (MTI) and fat suppression T 2WI (FS-T 2WI) in predicting the clinical activity of Graves ophthalmopathy (GO). Methods:From October 2020 to July 2021, 64 GO patients were prospectively enrolled in the First Affiliated Hospital of Nanjing Medical University. According to the clinical activity score (CAS), the patients were divided into active group (CAS≥3, 39 patients and 78 eyes) and inactive group (CAS<3, 25 patients and 50 eyes). The coronal MTI and FS-T 2WI were scanned for pre-treatment assessment. Magnetization transfer ratio (MTR) of extraocular muscles, and signal intensity ratio (SIR) between extraocular muscles and temporalis were measured, respectively. The independent-sample t-test was used to compare the MTR and SIR between two groups. The correlations between MRI parameters and CAS were analyzed using Spearman correlation analysis. The receiver operating characteristic (ROC) curve was performed to evaluate the value of each and combined parameters for predicting the clinical activity of GO. The DeLong test was used to compare the area under the curve (AUC). Results:The MTR of active group and inactive group were 0.45±0.04 and 0.51±0.04, respectively, the difference was statistically significant ( t=7.62, P<0.001). The SIR were 3.4±0.6 and 2.6±0.5, respectively, and the difference was also statistically significant ( t=-8.20, P<0.001). MTR was negatively correlated with CAS ( r=-0.46, P<0.001), while SIR was positively correlated with CAS ( r=0.63, P<0.001). The AUC of MTR, SIR and the combination of MTR and SIR for predicting the clinical activity of GO were 0.840, 0.845 and 0.905, respectively. The combination of MTR and SIR showed higher performance than MTR or SIR alone, and the differences were statistically significant ( Z=2.61, P=0.009; Z=2.15, P=0.032). Conclusions:The quantitative parameters of MTI and FS-T 2WI, namely MTR and SIR, can be used to evaluate the clinical activity of GO. Integrating MTI and FS-T 2WI can improve the diagnostic efficiency.

Application of mixed teaching mode based on SPOC and interactive tool in course of nursing bilingual education / 中华医学教育探索杂志

Objective:To explore the application of mixed teaching mode based on small private online course (SPOC) and interactive tool in course of obstetric and gynecological nursing bilingual education.Methods:Nursing undergraduates from Batch 2018 of Chongqing Medical University were recruited in the study, with 336 students in the intervention group and 332 students in the control group. Mixed teaching method based on the SPOC and interactive tool was used for teaching in the intervention group, and traditional teaching methods were used in the control group. At the end of the course, formative evaluation indicators, such as students' academic performance, online study and students' classroom performance were compared between the two groups. SPSS 26.0 was used to perform t test and chi-square test of the data. Results:The final scores of the intervention group were (67.84±8.65) points, compared with the control group [(66.50±7.29) points]; the bilingual section scores of the intervention group were (5.32±1.90) points, compared with the control group [(4.95±1.92) points], with statistically significant differences between the two groups ( P<0.05). The online study and students' classroom performances of the intervention group were better than those of the control group ( P<0.05). Most students of the intervention group believed the mixed teaching method based on the SPOC and interactive tool could develop the ability of autonomous learning, improve the professional achievement and enhance the level of English. Conclusion:The mixed teaching method based on the SPOC and interactive tool can develop the students' ability of autonomous learning and enhance the teaching effect.

Retrospectively analysis of the effect of low-dose aspirin on primary prevention of non-fatal myocardial infarction and cerebral infarction in patients with type 2 diabetes mellitus / 中国临床药理学与治疗学

AIM: To investigate the effect of low-dose aspirin on primary prevention of non-fatal myocardial and cerebral infarction in patients with type 2 diabetes mellitus. METHODS: From January 2015 to December 2016,40-90 years old patients with type 2 diabetes were treated in the Department of Endocrinology of Yijishan Hospital of Wannan Medical College for more than 2 times (the interval of hospitalization was more than 3 months) , we use the hospital's his system to search out-patient and in-patient files, patients were divided into aspirin group and non-aspirin group according to the use of low-dose aspirin within 1 year after the first visit, the basic data of the first visit were collected: name, sex, age, course of diabetes, systolic and diastolic blood pressure, patients were recorded for laboratory markers including fasting blood glucose, glycated hemoglobin, triglyceride, total cholesterol, Low-density lipoprotein, high-density lipoprotein, creatinine, and platelets, complications such as hypertension, coronary heart disease, atrial fibrillation, hyperlipidemia, diabetic nephropathy and arteriosclerosis were recorded. A Chi square test and a Cox proportional hazard model were used to compare baseline data and cerebrovascular disease after the first use of aspirin. RESULTS: Of the 4 176 patients, 2 137 were type 2 diabetes, 417 were eligible for admission, including 198 males, 219 females, 224 aspirin users and 193 non-users. There was no significant difference in the incidence of cerebral infarction between the aspirin group and the non-aspirin group (χ2=0.820, P=0.365). The incidence of non-fatal myocardial infarction was lower than that of the aspirin non-aspirin group (χ2=10.099, P=0.01) , the incidence of massive hemorrhage was significantly higher than that of aspirin-free group χ2=5.425, P=0.020) . In a subgroup analysis of aspirin use, patients younger than 60 years of age had a lower incidence of ischemic stroke (cerebral infarction) and a risk ratio of 0.428 (95%CI: 0.255-0.719, P=0.001) compared with patients older than 60 years of age, the incidence of cerebral infarction was higher in female patients with a risk ratio of 1.574 (95%CI: 1.018-2.434, P=0.041). CONCLUSION: In this study of patients with type 2 diabetes, low-dose aspirin reduced the incidence of nonfatal myocardial infarction but had no significant effect on the incidence of nonfatal ischemic stroke, and significantly increase the incidence of major bleeding events, we should reconsider the use of low-dose aspirin as a potential benefit of nonfatal cerebral infarction in patients with type 2 diabetes.

Oral Chinese Patent Medicines for Hyperlipidemia： A Scoping Review of Clinical Evidence / 中国实验方剂学杂志

To summarize the status quo of clinical evidence on oral Chinese patent medicine in the treatment of hyperlipidemia through scoping review and thereby provide a reference for clinical application and decision-making in health care. Proprietary Chinese medicines for the treatment of hyperlipidemia （dyslipidemia） were retrieved from relevant catalogs and then screened based on their instructions. Articles on the selected Chinese patent medicines were searched from Chinese and english electronic databases and screened according to the inclusion criteria， followed by data extraction and analysis. The results were described with text and graphs. ①A total of 32 Chinese patent medicines and 1 010 related articles were screened out. ②All the included Chinese patent medicines were made from Chinese medicinal materials， of which 5 were Chinese medicinal extracts，and the remaining 27 were pure Chinese medicinal preparations （the compositions of 1 prescription is confidential）. ③As indicated in the instructions， all the 32 Chinese patent medicines can be used to treat hyperlipidemia with the main syndrome of combined phlegm and blood stasis， and the main effect of them is activating blood and resolving stasis. ④Among the 32 medicines， Xuezhikang tablets （Capsules） and Gypenosides Tablets have the lowest price. ⑤For the 328 key clinical studies， 248 were randomized controlled trials and 80 non-randomized controlled trials. ⑥As for the sample size， randomized controlled trials generally included 28-579 cases， and non-randomized controlled trials 24-152 cases. Clinical studies with more than 200 cases accounted for 9.3% （12/129）. ⑦The most common method was the comparison of the intervention effect of Chinese patent medicine and western medicine （36.5%） and Atorvastatin Calcium Tablets was the preferred western medicine control. The observation duration was generally 56 days （8 weeks）. ⑧In clinical practice， the absolute value of blood lipid decrease and （total） effective rate were often used to evaluate the efficacy， and the effective rate was generally determined based on Clinical Guidelines for New Chinese Medicines. The overall quality of clinical studies on oral Chinese patent medicines is uneven and there is a lack of high-quality clinical evidence. Moreover，there are the risks of unreasonable use and uneasy use of Chinese patent medicine.It is recommended that researchers on proprietary Chinese medicine should further broaden the research ideas，focus on the top-level design of the research plan， and standardize the research process，thereby provide high-quality research evidence for the clinical use of proprietary Chinese medicine. Moreover， more efforts should be made to establish a sound mechanism for information collection and feedback of proprietary Chinese medicine， so as to reduce the risk of uneasy use.We hope that in-depth investigation and discussion should be launched by price， economy， quality evaluation， and other departments headed by the supervision department to make the price of Chinese patent medicine reasonable and fair， thereby promoting the rational use of Chinese patent medicine.

Multicenter study of the clinicopathological features and recurrence risk prediction model of early-stage breast cancer with low-positive human epidermal growth factor receptor 2 expression in China (Chinese Society of Breast Surgery 021) / 中华医学杂志(英文版)

BACKGROUND@#: Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.@*METHODS@#: Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed.@*RESULTS@#: Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880).@*CONCLUSIONS@#: Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.@*TRIAL REGISTRATION@#: ChiCTR.org.cn, ChiCTR2100046766.

Analysis of bile bacterial diversity in patients with recurrent common bile duct stones / 中华消化内镜杂志

Objective:To compare the bile bacterial diversity in patients with different types of common bile duct stones (CBDS).Methods:A total of 45 patients with CBDS diagnosed by abdominal ultrasound, abdominal CT and (or) magnetic resonance cholangiopancreatography (MRCP) and treated by endoscopic retrograde cholangiopancreatography (ERCP) in the First Affiliated Hospital of Air Force Medical University from August 2017 to January 2018 were divided into the non-stone (NS) group, the primary cholesterol stone (PCS) group, the primary pigment stone (PPS) group, and the recurrent stone (RS) group. 16S rRNA sequencing was used to analyze the microbile community structure and diversity in bile which was collected before contrast medium injection.Results:Thirty-three patients were in the non-RS group (8 in the NS group, 8 in the PCS group, and 17 in the PPS group) and 12 were in the RS group. The proportion of patients with intra-diverticular papilla [41.67% (5/12) VS 3.03% (1/33), χ2=8.27, P=0.004], loose stones [91.67% (11/12) VS 36.36% (12/33), χ2=10.77, P=0.001] and pigmental stones [100.00% (12/12) VS 51.52% (17/33), χ2=7.04, P=0.008] were significantly higher in the RS group than those in the non-RS group. There was no significant difference in other baseline data ( P>0.05). At the phylum and genus level, the bacterial abundance was similar in the RS and PPS group. Alpha and Beta diversity analysis showed that the microbial diversity was similar between the RS and PPS group, both of which were lower than those in the NS and PCS group ( P<0.05). MetaStat analysis revealed that Helicobacter pylori was the dominant bacteria in the RS group, and Proteobacteria and Escherichia coli were the dominant bacteria in both RS and PPS groups. Conclusion:Bacterial abundance of bile in the RS group is similar to that of the PPS group, but the diversity of biliary bacteria flora in the RS group and PPS group are significantly lower than those in the PCS group and NS group. Helicobacter pylori is the dominant biliary bacteria in the RS group.