Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To construct a clinical skills practice training model for pelvic floor rehabilitation specialist nurses based on the Taylor model, providing reference for cultivating the practical abilities of pelvic floor rehabilitation nurses.Methods:Based on the Taylor model, a preliminary draft of the clinical skills practice training model for pelvic floor rehabilitation specialist nurses was formulated through literature review, semi-structured interviews, and group discussions. From July to August 2023, 17 experts in nursing education, medical care, and pelvic floor rehabilitation nursing were invited to conduct two rounds of Delphi expert consultations to determine the various indicators of the training model. Analytic hierarchy process was used to determine the weights of indicators at all levels.Results:In the two rounds of consultation, the effective response rates of the questionnaires were all 100.00% (17/17), and the expert authority coefficients were 0.876. Kendall harmony coefficients of various indicators were 0.106 to 0.235 and 0.204 to 0.235 ( P<0.05). A clinical skills practice training model for pelvic floor rehabilitation specialist nurses was ultimately developed, which included three primary indicators, 12 secondary indicators, and 32 tertiary indicators. Analytic hierarchy process showed that the consistency ratios of each matrix for the tertiary indicators were all less than 0.100, passing the consistency test. Conclusions:The clinical skills practice training model for pelvic floor rehabilitation specialist nurses constructed highlights nursing characteristics, has high reliability and practicality, and can provide reference for practical training of pelvic floor rehabilitation skills.

Objective:To analyze the prognosis,clinicopathological characteristics,and genetic mutation features of patients with very low-and low-risk gastrointestinal stromal tumors(GISTs).Methods:A retrospective data collection of 433 patients with very low-and low-risk GISTs,diagnosed by pathology after surgical or endoscopic resection at Tianjin Medical University Cancer Institute&Hospital,was conduc-ted to analyze clinical pathology and prognosis.Results:Compared with low-risk GIST,a higher proportion of patients with very low-risk GIST had gastric GISTs,a Ki-67 index≤3%,and 0-1 mitotic indexes/5 mm2,whereas the proportion of patients with small intestinal GIST was low(all P<0.05).Genetic testing was performed in 118 patients,and there was no significant difference in the mutation types and KITmutation types between low-risk and very low-risk GISTs(all P>0.05).Patient follow-up was conducted on 87 very low-risk and 210 low-risk GIST pa-tients without other concurrent diseases,with a median follow-up of 86(27-158)months.None of the patients with very low-risk GISTs showed progression;three cases of low-risk GIST had recurrence or metastasis,with progression-free survival(PFS)ranging from 27 to 84 months.The mitotic indices of the primary tumors in these three patients were all 4/5 mm2,which is close to the critical value between the low-and intermediate-risk GIST mitotic indices,and all had KIT exon11 mutations.After the first progression,these three patients were treated with imatinib,and all survived until the end of follow-up,with overall survival ranging from 116 to 155 months.Conclusions:Among patients with low-risk GISTs,a very small number with high mitotic indices may have the potential for recurrence or metastasis,but after re-currence or metastasis,they can still maintain long-term,high-quality survival through targeted therapy,surgery,and other treatment meth-ods.The possibility of postoperative progression in very low-risk patients with GIST is extremely low,and the follow-up interval can be ap-propriately extended to reduce medical costs and alleviate the psychological burden on the patients and their families.

Objective To observe the effect of Danshen injection (DSI) on pulmonary fibrosis in silicosis mice, and to analyze the differential metabolic pathway on pulmonary fibrosis in silicosis using DSI by urine metabolomics. Methods The specific pathogen free C57BL/6J mice were randomly divided into control group, silicosis model group, DSI prevention group and DSI treatment group. The mice in the last three groups were given 1 mL silica suspension with a mass concentration of 50 g/L by the one-time non-exposed tracheal method, and the mice in the control group were not given any treatment. Subsequently, mice in the DSI prevention group and the DSI treatment group were given intraperitoneal injection of DSI with a dose of 5 mL/kg body weight from 24 hours after exposure to dust and from the 29th day after exposure to dust, respectively, once per day until the 56th day after exposure. Mice in the other two groups were not treated. After DSI intervention, the lung histopathological changes of mice in all groups were evaluated. The components of mouse urine metabolites were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-fight mass spectrometry method. Human Metabolome Database was used to screen the potential differential metabolites (DMs). The related metabolic pathways were analyzed using MetaboAnanlyst 5.0 Web analytics platform. Results The result of hematoxylin-eosin staining and Van Gieson staining of mouse lung tissues showed that the pulmonary alveolar structure destroyed, typical fibrotic nodules appeared, collagen fiber deposition increased, and clumpy accumulation in the silicosis model group, compared with the control group. Compared with the silicosis model group, the degree of pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI prevention group was obviously reduced to close to the control group, while pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI treatment group were also reduced, although the outcome was not as good as that in the DSI prevention group. The result of urine metabolomics analysis identified four DMs in the model group and control group, seven DMs were identified in the DSI prevention group and silicosis model group, seven DMs were identified in the DSI treatment group and silicosis model group. A total of three DMs pathways related to pulmonary fibrosis in silicosis model group and the protective effect of DSI prevention group were identified, including D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways (all P<0.01). Conclusion DSI treatment in any time point can interfere the process of pulmonary fibrosis in the silicosis mice, while the interference is more effective in the DSI group treated right after dust-exposure. DSI interferes with the urinary metabolism pathway of silicosis mice, and the D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways may participate in the inhibiting process of early pulmonary fibrosis in silicosis mice by DSI.

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Objective:To evaluate and compare the clinical efficacy and safety of three different medicated eye patches in the treatment of Demodex blepharitis. Methods:A multicenter, randomized, double-blind, parallel-controlled clinical trial was conducted.A total of 140 patients (280 eyes) with Demodex blepharitis were recruited in Shanghai Jing'an District Shibei Hospital, Xi'an Fourth Hospital and Kunming First People's Hospital from July 2021 to December 2022.The affected eyes were randomly divided into tea tree oil group, okra oil group, basal fluid control group and metronidazole group by the random number table method.Eye patches containing 20% tea tree oil, 1% okra oil, prepared base solution and 2% metronidazole were applied to the eyes for 28 days by the double-blind method.The count of Demodex was evaluated before treatment and on days 14 and 28 of treatment.Ocular surface symptoms were scored according to Ocular Surface Disease Index (OSDI). The degree of congestion at the eyelid margin and cylindrical dandruff at the root of eyelashes were scored under a slit lamp microscope.The effective rate was calculated according to the comprehensive scores above, and the adverse reactions of the subjects were observed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Jing'an District Shibei Hospital (No.YL-20200320-05). All the subjects were informed of the significance, purpose and method of the study.Written informed consent was obtained from each subject before any medical examination. Results:All subjects completed the treatment and follow-up, and the loss to follow-up rate was 0%.After 14 and 28 days of treatment, the Demodex count was significantly decreased in all groups compared with before treatment (all at P<0.05). After 28 days of treatment, the number of Demodex in tea tree oil group, okra oil group and metronidazole group were significantly lower than that in basal fluid control group, with statistically significant differences (all at P<0.05). The OSDI score, palpebral margin congestion score and cylindrical dandruff score on 14 and 28 days after treatment in tea tree oil group, okra oil group and metronidazole group were significantly lower than before treatment, showing statistically significant differences (all at P<0.05). After 28 days of treatment, the effective rates of tea tree oil group, okra oil group and metronidazole group were 71.4%, 71.4% and 62.9%, respectively, which were significantly higher than 25.7% in basal solution control group.No serious local or systemic adverse reactions were found during the treatment and follow-up. Conclusions:Eye patches containing tea tree oil, okra oil and metronidazole have significant effects on the treatment of Demodex blepharitis, which can improve the biological environment of the palpebral margin and eliminate the inflammation related to blepharitis.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.