As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

The compilation instructions for the Expert Consensus on Clinical Application of Yifei Zhike Capsules systematically expound the development background， methodological framework， and core achievements of this consensus. In view of the problems existing in the clinical application of Yifei Zhike Capsules， such as insufficient efficacy evidence and lack of standardized syndrome differentiation， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences took the lead and collaborated with 21 tertiary grade-A hospitals and research institutions across China to form a multidisciplinary expert group （comprising 30 experts in clinical medicine， pharmacy， and methodology）. The compilation work was carried out in strict accordance with the World Health Organization （WHO） guidelines， the GB/T 1.1-2020 standard， and the writing specifications for the explanatory notes of expert consensus on clinical application of Chinese patent medicines. Through systematic literature retrieval （including 32 studies， with 24 clinical studies）， Grading of Recommendations Assessment， Development and Evaluations （GRADE）-based evidence grading， and multiple rounds of discussions using the nominal group method （25 experts voted to determine 17 clinical questions）， 5 evidence-based recommendations and 11 expert consensus suggestions were formed. It is clarified that this medicine （Yifei Zhike Capsules） is applicable to the treatment of expectoration/hemoptysis in acute and chronic bronchitis and the adjuvant treatment of pulmonary tuberculosis. It is recommended that it can be used alone or in combination with anti-tuberculosis drugs. The safety evaluation shows that this medicine mainly induces the following adverse reactions： mild gastrointestinal reactions （such as nausea and abdominal pain） and rashes. The contraindicated populations include pregnant women and women during menstruation. The compilation process of the consensus underwent three rounds of expert letter reviews， two rounds of peer reviews， and quality control assessments to ensure methodological rigor and clinical applicability. In addition， through policy alignment， academic promotion， and a dynamic revision mechanism， the standardization of clinical application was promoted， providing a demonstration for the evidence-based transformation of characteristic therapies of Miao medicine.

Objective To explore the distribution characteristics of endogenous metabolites in Crocus sativus L. corms from different origins. Methods A method based on desorption electrospray ionization mass spectrometry imaging and optimized sample pretreatment was developed for directly visualize metabolites in C. sativus corms. Results In situ characterization of metabolites such as flavonoids, organic acids, amino acids, carotenoids, and cyclic enol ether terpene glycosides was achieved. L-Citruline, phenylacetylglycine, sativol, and geniposide were specifically distributed in the corms. Apigenin 7-（6''-O-acetyl）-glucoside, isorhamnetin-3-O-β-D-Glucoside, dhurrin 6'-glucoside, and Apigenin 7-O-diglucuronide were mainly distributed in the terminal bud. For compounds distributed in the corms, the highest abundance was found in corms from Shanghai, followed by Zhejiang and the lowest from Anhui. Conclusion The distribution of metabolites in different parts of C. sativus corms from different origins and the same origin varies significantly. Flavonoids and flavonoid derivatives such as isorhamnetin-3-O-β-D-Glucoside and apigenin derivatives are mainly distributed in the terminal buds, in addition, the natural plant protection agent dhurrin 6'-glucoside is also mainly distributed in the terminal corms, whereas amino acids, which are used as energy and material supplies, are mainly accumulated in the corms.

BACKGROUND:Irreducible femoral neck fracture was difficult to obtain anatomic reduction.As a new type of internal fixation,the femoral neck system is still blank for the treatment of non-anatomical reduced femoral neck fractures. OBJECTIVE:To explore the biomechanical stability of femoral neck system internal fixation under nonanatomical reduction in the treatment of femoral neck fractures based on finite element analysis. METHODS:CT data of the hip joint of a healthy female adult were obtained.Anatomical reduction of femoral neck fracture models with Pauwels angles of 30°,50°,and 70° were established using Mimics 21.0,Geomagic Wrap 2021,and SolidWorks 2020.The fracture proximal ends of the three anatomical reduction models were shifted upward by 2 mm along the fracture line,and three positive buttress models with different Pauwels angles were obtained.In the same way,three negative buttress models were acquired by shifting downward by 2 mm.SolidWorks 2020 was used to make the femoral neck system internal fixation,and the nine femoral neck fracture models were assembled with the femoral neck system.Then Ansys 19.0 was used for finite element analysis.The displacement distribution and maximum displacement,stress distribution and maximum stress of the femur and femoral neck system were recorded under 2100 N stress. RESULTS AND CONCLUSION:(1)When Pauwels angles were 30°,50°,and 70°,the maximum stresses of the femoral neck system appeared to be concentrated at the junction of the sliding hip screw and anti-rotation screw.The maximum femur stresses appeared to be concentrated in the medial cortex of the femur.The maximum displacement was concentrated at the upper of the femoral head and femoral neck system.(2)When Pauwels angles were 30° and 50°,the maximum displacement and maximum stress of the femoral neck system and femur were:negative buttress>anatomical reduction>positive buttress.(3)When Pauwels angle was 70°,the maximum displacement and maximum stress of the femoral neck system were:negative buttress>anatomical reduction>positive buttress;the maximum displacement and maximum stress of the femur were:negative buttress>positive buttress>anatomical reduction.(4)With the increase of Pauwels angle,the biomechanical advantage of the positive buttress was weakening.However,it was better than a negative buttress.When Pauwels angle was 30°,positive buttress was more stable than anatomical reduction.When Pauwels angle was 50°,the biomechanical difference between positive buttress and anatomical reduction became smaller.When Pauwels angle was 70°,the stability of anatomical reduction was slightly better than positive buttress.(5)If it was difficult to achieve anatomical reduction of femoral neck fracture during operation,but the positive buttress had been displaced within 2 mm,the femoral neck system could be used to offer stable mechanical fixation.It is necessary to avoid negative buttress reduction.

Objective:To evaluate the validity and reliability of Positive Beliefs About Rumination Scale(PBRS)in Chinese college students.Methods:A total of 968 college students were selected.Exploratory factor a-nalysis,criterion validity and internal consistency reliability test were performed on sample 1(n=496).The Rumi-native Responses Scale(RRS),Metacognitions Questionnaire(MCQ)and Beck Depression Inventory-Ⅱ(BDI-Ⅱ)were used as criteria for criterion validity test.Confirmatory factor analysis and Measurement invariance across gen-der were performed on sample 2(n=472).The 87 college studentsin sample 1 were retested 6 weeks later.Results:The exploratory factor analysis found 1 factor,which explained 54.39％of the total variance.The confirmatory factor analysis showed that the 1-factor model fitted well(x2/df=3.38,CFI=0.962,TLI=0.940,SRMR=0.043,RMSEA=0.071).The scores of the Positive Beliefs About Rumination Scale were positively cor-related with the scores of RRS,MCQ and BDI-Ⅱ(ICC=0.37,0.41,0.12,Ps＜0.01).The Cronbach α coefficient of the Positive Beliefs About Rumination Scale was 0.89.The retest reliability(ICC)of the Positive Beliefs About Rumination Scale was 0.72.The configural,weak,strong and strict invariance of the PBRS across gender were all acceptable(△CFI,△TLI＜0.01).Conclusion:The Positive Beliefs About Rumination Scale has good validity and reliability in Chinese college students.

AIM:To investigate the effects of exercise preconditioning(EP)combined with electroacupunc-ture(EA)on learning and memory ability of rats with vascular dementia(VD),and to explore role of hippocampal ferrop-tosis in this process.METHODS:Seventy-two male SD rats were randomly divided into non-EP group and EP group,with 36 rats in each group.The rats were subjected to EP,and subsequently to establish the VD model.The rats from non-EP group were randomly divided into sham group,model group(VD group)and VD-EA group,each with 12 rats,while those in EP group were randomly divided into EP-sham group,EP-VD group and EP-VD-EA group,each with 12 rats.All rats in EP group underwent 4 weeks of swimming exercise training,5 d per week,30 min per day.At the end of the 4th week,the rats in VD,EP-VD,EP-VD-EA and VD-EA groups were used to induce the VD model,and the rats in sham and EP-sham groups received a sham surgery to simulate the VD model.On the 7th day after successful modeling,the rats in EP-VD-EA and VD-EA groups were treated with EA for 4 weeks,6 d per week,30 min per day.At the end of the inter-vention,the learning and memory ability of the rats was evaluated using Morris water maze.Neuron morphology in the CA1 area of rat hippocampus was observed through Nissl staining.Ferrous ion(Fe2+),malondialdehyde(MDA)and re-duced glutathione(GSH)contents in the rat hippocampal tissues were quantified using the colorimetric assay.The expres-sion levels of ferroptosis-related proteins,nuclear factor E2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4),in the hippocampal tissues were quantified by Western blot method.RESULTS:Compared with sham group,the rats in VD group exhibited longer mean evasion latency and decreased number of traversals across the plateau(P<0.01).The neurons in the CA1 region of the hippocampus were loose and disorganized,exhibiting an irregular cellular morphology.The hippocampal Fe2+and MDA content was elevated,and the GSH content was reduced(P<0.01).The protein levels of hippocampal Nrf2 and GPX4 were decreased(P<0.01).Compared with VD group,the rats in EP-VD,EP-VD-EA and VD-EA groups showed a shorter average escape latency and an increased number of traversals across the plateau(P<0.05).Neurons in the hippocampal CA1 area were more neatly arranged,showing regular cellular morphology.The hip-pocampal Fe2+and MDA contents of the rats in EP-VD group were significantly reduced(P<0.01),while the GSH content was elevated(P<0.05).Hippocampal Fe2+and MDA contents were significantly reduced and GSH contents were signifi-cantly increased in EP-EA and EA groups(P<0.01).The protein levels of hippocampal Nrf2 and GPX4 in EP-VD,EP-VD-EA and VD-EA groups were significantly increased(P<0.01).CONCLUSION:Exercise preconditioning combined with EA improves learning and memory ability in VD rats by reducing hippocampal intra-neuronal iron overload,maintain-ing organismal redox homeostasis,and inhibiting ferroptosis.

Objective Apply modified bilateral carotid artery ligation to establish a VD rat model to observe changes in cerebral blood flow and expression of angiogenic proteins.Methods Thirty-six SD male rats were randomly divided into a sham group(n = 18)and model group(n = 18).In the sham group,only the bilateral carotid artery was isolated without ligation,whereas in the model group,the bilateral carotid artery was ligated to establish the VD model.The Morris water maze behavior test was applied before and 14 days after modeling.Variation in cerebral blood flow was detected by laser speckle contrast imaging.Protein expression of HIF-1α,VEGF,and HO-1 was detected by Western Blot.IL-4 and IL-10 contents were measured by ELISA.Results At 14 days after modeling,escape latency was significantly prolonged and the frequency of crossing the platform had significantly decreased in the model group compared with the sham group(P<0.05).At 2 hours,3 days,and 7 days after modeling,cerebral blood flow in the model group was significantly lower than that in the sham group(P<0.05).At 14 and 21 days after modeling,no significant difference was found in cerebral blood flow between sham and model groups(P>0.05).In the model group,cerebral blood flow was decreased to a minimum at 2 hours after modeling(P<0.05)and then began to recover.The peak of recovery occurred at 3～7 days after modeling and returned to the level before modeling on day 14 after modeling.At postoperative day 21,expression of HIF-1α,VEGF,and HO-1 proteins in the hippocampus of the model group was increased remarkably(P<0.05)and the serum contents of IL-4 and IL-10 in the model group were significantly increased compared with those in the sham group(P<0.05).Conclusions The variation in cerebral blood flow in the VD rat model established by the modified bilateral carotid artery ligation was dependent on time.At postoperative day 21,HIF-1α,VEGF,and HO-1 in the hippocampus were increased significantly,which was accompanied by increased levels of IL-4 and IL-10.

OBJECTIVE: To investigate the chemical constituents from the leaves of Jatropha curcas and evaluate their inhibition on lipopolysaccharide (LPS)-activated BV-2 microglia cells. METHODS: The n-BuOH extract of the leaves of J. curcas was isolated by macroporous adsorption resin, silica gel, ODS, column chromatography and semi-preparative HPLC. The structures of the compounds were identified by MS, NMR, ECD, and other spectroscopic methods. In addition, anti-neuroinflammatory effects of isolated compounds were evaluated by measuring the production of nitric oxide (NO) in over-activated BV-2 cells. RESULTS: Seventeen compounds, including (7R,8S)-crataegifin A-4-O-β-D-glucopyranoside ( 1), (8R,8'R)-arctigenin ( 2), arctigenin-4'-O-β-D-glucopyranoside ( 3), (-)-syringaresinol ( 4), syringaresinol-4'-O-β-D-glucopyranoside ( 5), (-)-pinoresinol ( 6), pinoresinol-4'-O-β-D-glucopyranoside ( 7), buddlenol D ( 8), (2R,3R)-dihydroquercetin ( 9), (2S,3S)-epicatechin ( 10), (2R,3S)-catechin ( 11), isovitexin ( 12), naringenin-7-O-β-D-glucopyranoside ( 13), chamaejasmin ( 14), neochamaejasmin B ( 15), isoneochamaejasmin A ( 16), and tomentin-5-O-β-D-glucopyranoside ( 17) were isolated and identified. Compounds 2, 4 and 8 significantly inhibited the release of NO in BV-2 microglia activated by LPS, with IC₅₀ values of 18.34, 29.33 and 26.30 μmol/L, respectively. CONCLUSION Compound 1 is a novel compound, and compounds 2, 3, 8, 14- 17 are isolated from Jatropha genus for the first time. In addition, the lignans significantly inhibited NO release and the inhibitory activity was decreased after glycosylation.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.