ObjectiveTo investigate the effect of astragaloside Ⅳ（AS-Ⅳ） on the proliferation of vascular smooth muscle cells（VSMCs） induced by angiotensin Ⅱ（Ang Ⅱ） based on solute carrier family 7 member 11/glutathione peroxidase 4（SLC7A11/GPX4） pathway. MethodsPrimary rat thoracic aortic VSMCs were cultured by tissue explant method， and the cell types were identified by immunofluorescence. Cell counting kit-8（CCK-8） was used to determine the optimal concentration and time of AS-Ⅳ after Ang Ⅱ stimulation. The experiment was divided into blank group， model group， AS-Ⅳ group（40 μmol·L^-1）， Erastin group（0.5 μmol·L^-1）， Erastin+AS-Ⅳ group（0.5 μmol·L^-1+40 μmol·L^-1）. The blank group was cultured in normal medium， the model group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1）， and each administration group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1） and the corresponding doses of drug. CCK-8 and plate clone formation assay were used to detect the proliferation of cells in each group， Prussian blue staining was used to detect cell iron deposition， the content of reactive oxygen species（ROS） in cells was detected by fluorescence probe method， the content of malondialdehyde（MDA） was detected by thiobarbituric acid（TBA） method， and the protein levels of SLC7A11 and GPX4 in each group were detected by Western blot. ResultsPrimary rat thoracic aortic VSMCs were successfully cultured by tissue explant method， and immunofluorescence detection showed that positive expression of α-smooth muscle actin（α-SMA） and negative expression of vimentin in the cells， identifying them as VSMCs. The optimal concentration and time of AS-Ⅳ determined by CCK-8 were 40 μmol·L^-1 and 24 h， respectively. Pharmacodynamic studies showed that compared with the blank group， the cell proliferation in the model group increased， the iron deposition in the cells increased， the contents of ROS and MDA increased， and the expression levels of SLC7A11 and GPX4 proteins decreased（P<0.05， P<0.01）. Compared with the model group， the cell proliferation of the AS-Ⅳ group was inhibited， the iron deposition in the cells was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. While in the Erastin group， the cell proliferation was increased， the iron deposition was increased， ROS and MDA contents were increased， and the expression levels of SLC7A11 and GPX4 proteins were decreased（P<0.05， P<0.01）. Compared with the AS-Ⅳ group， Erastin+AS-Ⅳ group showed increased cell proliferation， increased iron deposition in cells， increased ROS and MDA contents， and decreased expression of SLC7A11 and GPX4 proteins（P<0.05）. Compared with the Erastin group， the cell proliferation in Erastin+AS-Ⅳ group was inhibited， the iron deposition was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. ConclusionAS-Ⅳ can inhibit ferroptosis by regulating the SLC7A11/GPX4 pathway， so as to weaken the proliferation of VSMCs， thus playing a role in the treatment of atherosclerosis.

Objective To systematically review whether mirror therapy(MT)intervention can effectively improve upper extremity motor function and activities of daily living(ADL)in stroke patients;whether its improvement is affected by pa-tients'age and disease course;and whether MT's influencing factors,such as intervention period,time,and fre-quency,have a dosage effect on upper extremity motor function and ADL. Methods Seven databases were searched,including Embase,Web of Science,PubMed,Cochrane Library,Wanfang data,VIP and CNKI from establishment to April,2023,and randomized controlled trials of MT for upper extremity motor function and ADL in stroke patients were screened.Quality assessment was performed using Physiothera-py Evidence Database(PEDro).Meta-analysis was performed using RevMan 5.4.1,and network meta-analysis was performed using R software,reticulated meta-analysis tables and cumulative probability tables were drawn for ranked comparisons,and funnel plots were drawn to test for publication bias of the outcome indicators using Stata 17.0 software.GRADE was used to evaluate the quality of evidence for the outcome indicators. Results A total of 13 papers(532 patients)were included.The PEDro score ranged from 6 to 8.Most of the literature did not report the blinding completely or did not implement allocation concealment,which might have some limita-tions.MT could improve the scores of Fugl-Meyer Assessment-Upper Extremities(n = 466,MD = 6.05,95%CI 3.44～8.66,P<0.001),Barthel index(n = 230,MD = 9.95,95%CI 6.23～13.68,P<0.001)and Functional Inde-pendence Measure(n = 147,MD = 4.17,95%CI 2.61～5.72,P<0.001)in stroke patients.Network meta-analysis showed that MT was more effective in upper limb motor function intervention for stroke patients aged 40 to 59 years with a disease course less than three months;and an intervention period less than four weeks,single inter-vention time less than 30 minutes,intervention duration daily more than 30 minutes and intervention twice daily might optimize the effects on upper limb motor function. Conclusion MT is effective on upper limb motor function and ADL in stroke patients,and the effect on upper limb mo-tor function is affected by the age and disease course of the patients,as well as the period,time and frequency of intervention.

BACKGROUND:The Yi people have used Sambucus adnata Wall to treat fractures,bruises,arthritis,etc.The author's group found that the active site aqueous extract(SAW-A)and dichloromethane extract(SAW-B)can promote fracture healing by promoting the expression of genes related to osteoblast proliferation,differentiation and maturation,differentiation and maturation.However,the therapeutic effect of methanol extract(SAW-C)at its active site on osteoarthritis is unclear. OBJECTIVE:To investigate the therapeutic effect of Sambucus adnata Wall extract on osteoarthritis,and to identify the effective targets of Sambucus adnata Wall extract in the treatment of osteoarthritis by network pharmacology technology. METHODS:A rat osteoarthritis model was replicated by anterior cruciate ligamentectomy and model rats were then treated with methanol extract of Sambucus adnata Wall by gavage for 21 days.On the 21st day after modeling,the knee joint of rats was detected by X-ray,the width of the knee joint was measured,oxidative stress indexes and inflammatory factors levels in serum and joint lavage fluid were detected,the morphology of the knee joint was observed by hematoxylin-eosin staining,full-thickness cartilage and hyaline cartilage thickness were measured,and the content of articular cartilage proteoglycan was observed by safranin O-fast green staining.The"drug-component-disease-target"network was constructed.Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis of effective targets were performed,and protein-protein interaction network maps were constructed using cytoscape software. RESULTS AND CONCLUSION:Sambucus adnata Wall extract could reduce tumor necrosis factor-α level in joint lavage fluid and serum levels of prostaglandin E2 and malondialdehyde,while increase the level of superoxide dismutase;relieve joint swelling caused by osteoarthritis;improve the histopathological state of articular cartilage,maintain the thickness of full-thickness articular cartilage,hyaline cartilage and the area of bone trabeculae in subchondral bone;and effectively prevent the loss of proteoglycans in articular cartilage and have a chondroprotective effect.Network pharmacological results showed that the methanol extract of Sambucus adnata Wall may have some targets related to inhibition of tumor necrosis factor,AKT1,interleukin-6,MAPK3,and SRC as well as inhibition of over-activation of EGFR signaling pathway and AGE-RAGE signaling pathway.

BACKGROUND:Previous studies showed that extracts of Sambucus adnata Wall.have the ability to promote the proliferation and differentiation of osteoblasts,fracture healing,anti-inflammatory and antioxidant effects,which can effectively alleviate the development of osteoarthritis.Vascular endothelial growth factor,on the other hand,is a biomarker for the evaluation of osteoarthritis severity. OBJECTIVE:To investigate the effect and mechanism of two extracts of Sambucus adnata Wall.(methanol extract SAW-ME and dichloromethane extract SAW-DCE)on angiogenesis in osteoarthritis. METHODS:(1)Rat models of osteoarthritis were established using anterior cruciate ligament transection and given SAW-ME and SAW-DCE.A sham group was set as a control.Immunohistochemistry and immunofluorescence were used to detect the changes of articular vascular endothelial growth factor A in joint tissue and vascular endothelial growth factor and"H"type blood vessels in serum of osteoarthritis rats.(2)Vascular endothelial cells EA.hy926 were used as the research object and intervened with SAW-ME and SAW-DCE.Cell proliferation was then detected by MTT assay.Vascular endothelial growth factor was used to induce EA.hy926 cells,and the model of angiogenesis was replicated.Cell scratch assay and tube formation assay were performed to study the role and mechanism.(3)EA.hy926 cells were used for transcriptome sequencing to analyze the characteristic changes of cell differential genes and related functions after SAW-DCE intervention. RESULTS AND CONCLUSION:(1)SAW-ME and SAW-DCE downregulated the expression of vascular endothelial growth factor A in the rat knee cartilage and reduced the formation of"H"type vessels in osteoarthritis rats.SAW-ME could significantly decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats(P<0.05).SAW-DCE could also decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats,but there was no significant change.(2)Both SAW-ME and SAW-DCE significantly inhibited vascular endothelial cell migration and tube formation,and downregulated the expression of Ang1 and Tie2 proteins.(3)Transcriptome sequencing analysis found that abnormal angiogenesis in osteoarthritis was related to the PI3K/AKT signaling pathway.(4)To conclude,SAW-ME and SAW-DCE can inhibit angiogenesis in the rat model of osteoarthritis,and the mechanism may be related to the Ang1/Tie2 and PI3K/AKT signaling pathways.

ObjectiveTo identify the chemical components of Houpo Wenzhongtang in vivo and in vitro and to analyze the pharmacokinetic properties of the index components in rats with deficiency-cold of spleen and stomach. MethodThe chemical components of Houpo Wenzhongtang was analyzed and identified by ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS）. Six rats were randomly selected from 18 SD rats as the blank group， and the remaining rats were given lard and cold vinegar for a long time to construct a rat model with deficiency-cold of spleen and stomach. After successful modeling， the rats were randomly divided into the model group and Houpu Wenzhongtang group（13.5 g·kg^-1， calculated as crude drug）. The administration group was given the corresponding dose of Houpu Wenzhongtang by gavage， and the blank group and the model group were given the same amount of distilled water by gavage. Enzyme-linked immunosorbent assay（ELISA） were used to measure gastrin（GAS） and motilin（MTL） levels in each group. At the same time， plasma samples were collected at different time points after administration， and blood-entry prototype components and metabolites of Houpo Wenzhongtang were analyzed by UPLC-Q-TOF-MS/MS. On this basis， plasma concentrations of magnolol， honokiol， alpinetin and hesperidin in Houpo Wenzhongtang were determined by ultra performance liquid chromatography coupled with triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）， and the pharmacokinetic parameters were calculated using DAS 2.0 software. ResultA total of 79 chemical components， including 44 flavonoids and 11 lignans， were identified in Houpo Wenzhongtang. Meanwhile， 18 blood-entry prototype components and 27 metabolites were identified， the main metabolic pathways of metabolites were glucuronidation， sulfation， oxidation and hydrolysis， and phase Ⅰ and phase Ⅱ were the two primary forms of metabolism. Pharmacokinetic results showed that among the four index components， the time to peak（t_max） values of magnolol and honokiol were consistent and exhibited similar drug metabolism characteristics， the t_max of alpinetin was the shortest， and the absorption rate was the fastest， which had the earliest peak plasma concentration levels， and hesperidin had the shortest mean residence time（MRT_0-t） and the highest metabolic rate in rats. ConclusionThis study clarifies the blood-entry prototype components and their metabolites of Houpo Wenzhongtang in the rat model of deficiency-cold of spleen and stomach， and reveals the pharmacokinetic characteristics of the main active ingredients， which can provide a scientific basis for the study of pharmacodynamic material basis of this formula and its clinical application in treating the syndrome of deficiency-cold of spleen and stomach.

Objective:To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China.Methods:From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis.Results:A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0–1. After receiving third- and fourth-line treatment, 50%–60% of patients maintained a good quality of life and 40%–50% of them maintained ECOG performance scores of 0–1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer.Conclusions:This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

Objective:To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China.Methods:From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis.Results:A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0–1. After receiving third- and fourth-line treatment, 50%–60% of patients maintained a good quality of life and 40%–50% of them maintained ECOG performance scores of 0–1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer.Conclusions:This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)erve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

Objective:To investigate the clinical application of multi-oil fat emulsion (SMOF) in preterm infants with necrotizing enterocolitis (NEC).Methods:Preterm infants with NEC admitted to the Neonatal Intensive Care Unit in our hospital between January 2017 and December 2022 were retrospectively included. According to the type of fat emulsion used, they were divided into SMOF group and medium and long chain triglycerides (MCT/LCT) group. The data of two groups were compared and analyzed.Results:A total of 69 preterm infants were included, 34 in the SMOF group and 35 in the MCT/LCT group. There were no significant differences between the two groups in the levels of total bilirubin, indirect bilirubin, direct bilirubin, bile acid and γ-glutamyl transferase ( P>0.05). There were no significant differences between the two groups in triglyceride, low density lipoprotein and total cholesterol ( P>0.05). There were no significant differences between the two groups in the C reactive protein level, procalcitonin level, and the time to normal C reactive protein ( P>0.05). There were no significant differences in incidence of complications between the two groups, including parenteral nutrition-related cholestasis, bronchopulmonary dysplasia, retinopathy of prematurity, and brain injury ( P>0.05). Conclusions:Compared with MCT/LCT, the application of SMOF did not show significant effect on liver function, inflammation, or incidence of complications (parenteral nutrition-related cholestasis, bronchopulmonary dysplasia and retinopathy of prematurity) in preterm infants with NEC. Multi-center studies with larger sample size are needed for further investigation.

OBJECTIVE To investigate the effect of arctiin （ARC）relieving lipopolysaccharide （LPS）induced inflammatory injury of human nasopharyngeal epithelial cells NP- 69. METHODS The effects of 24 h treatment of 0.000 1，0.001，0.01，0.1， 1.0，10 μmol/L ARC on the proliferation of NP-69 were determined by MTS method. After 0.01，0.1，and 1.0 μmol/L ARC was applied to NP- 69 for 24 h and NP- 69 was pre-treated with 0.01，0.1 and 1.0 μmol/L ARC for 24 h，and then stimulated with 1.0 μg/mL LPS for 24 h，scratch tests were used to detect cell migration in both experiments. LPS stimulated NP- 69 to establish an inflammation injury model. The levels of nitric oxide （NO），tumor necrosis factor α（TNF-α）interleukin-6（IL-6），and IL- 1β in cell supernatants were detected ，and mRNA and protein expression of zonula oecludens protein 1（ZO-1），β-defensin 3（BD3）， Janus kinase 1 （JAK1），signal transducer and activator of transcription 3 （STAT3） in cell supernatant were also detected. RESULTS Compared with normal group ，0.000 1，0.001，0.01，0.1，1.0，10 μmol/L ARC had no effect on the proliferation of NP-69 after 24 h treatment （P＞0.05）. ARC （0.1，1.0 μmol/L）could significantly promote the rate of cell migration （P＜0.05）. For the inflammatory injure of NP- 69 cells stimulated by LPS ，ARC（1.0 μmol/L）could significantly reduce the release of NO ， TNF-α and IL-6（P＜0.05），significantly increased mRNA and protein expression of ZO- 1 and BD 3 but decreased mRNA and protein expression of STAT 3（P＜0.01 or P＜0.05）. CONCLUSIONS ARC has the effect of reducing the inflammatory injury of NP-69 cells induced by LPS ，promoting the physical and immune defense ability of the nasal mucosa epithelial barrierunder inflammatory environment. The mechanism of action may be related to inhibiting IL- 6/JAK1/STAT3 signaling pathway.