Six compounds were isolated from the ethyl acetate fraction of Citri Sarcodactylis Fructus by using various column chromatographic methods, such as MCI Gel CHP-20, ODS, Sephadex LH-20, silica gel and semipreparative HPLC. Their structures were identified to be citrusin G (1), citrusin H (2), citrusin E (3), syringin (4), coniferin (5), methylconiferin (6) by NMR, HR-ESI-MS, UV, IR spectra. Compounds 1 and 2 were new secondary metabolism products and 3-6 were obtained from the titled material for the first time. Compound 1 showed anti-renal fibrosis activity in TGF-β1-induced kidney proximal tubular cells.

Objective: To explore the causal link of cumulative ecological risk and future orientation with health risk behaviors among higher vocational college students, so as to provide reference for reducing and preventing health risk behaviors among higher vocational college students. Methods: A longitudinal follow up study was conducted on 612 students using convenience sampling from 2 vocational colleges in Hunan Province. The Cumulative Ecological Risk Scale, Future Orientation Scale, and Health Risk Behavior Scale were used during three follow up visits (T1: September 2022, T2: June 2023, T3: March 2024), and a cross lagged panel model was constructed to examine the longitudinal causal relationship of cumulative ecological risk, future orientation and health risk behaviors. Analysis of longitudinal intermediary effect between variables by Bootstrap. Results: The cumulative ecological risk scores of T1, T2 and T3 among higher vocational college students were (2.94±1.44,2.99±1.63,3.02±1.54), future orientation scores (40.49±4.71,41.51±5.72,41.06±4.35) and health risk behavior scores (3.73±2.01,3.49±2.00,3.23±2.00). The results of repeated measures ANOVA showed that the future orientation score of T2 was higher than that of T1, and the main effect of measurement time was statistically significant ( F=5.09，P＜0.01,η 2=0.02). The health risk behavior score of T1 was higher than that of T2, and the health risk behavior score of T2 was higher than that of T3, and the main effect of measurement time was statistically significant ( F=10.12，P＜0.01,η 2=0.03).The cross lagged model showed good adaptability, with χ 2/df =7.20 ( P <0.01), relative fitting indicators GFI=0.98, CFI=0.99, TLI=0.96, IFI=0.99, NFI =0.99, and absolute fitting indicator RMSEA =0.06. Among them, the T1, T2 cumulative ecological risk showed negatively predictive effects on T2, T3 future orientation ( β =-0.24, -0.47 ), and T1, T2 cumulative ecological risk positively predicted T2, T3 health risk behavior ( β =0.20, 0.24), while T1, T2 future orientation negatively predicted T2, T3 health risk behavior ( β =-0.25, -0.18) ( P ＜0.01). Bootstrap test analysis found that T2 future orientation had a longitudinal mediating effect ( β=0.04, P ＜0.01) on the T1 cumulative ecological risk and T3 health risk behavior. Conclusions The accumulation of ecological risk among higher vocational college students can positively predict health risk behaviors, while future orientation can negatively predict healthrisk behaviors. Moreover, future orientation plays a longitudinal mediating role between accumulated ecological risks and health risk behaviors.

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.

Objective To explore the effects of nicotinamide mononucleotide （NMN） on hypertensive rats. Methods Two rat hypertension models including spontaneously hypertensive rats（SHR）and two-kidney two-clip （2K2C） rats were used to be given single, long-term or lifelong administration of NMN respectively. NMN’s effects were assessed comprehensively by monitoring survival time, blood pressure levels, and the extent of organ damage in hypertensive model rats. Results It was revealed that NMN did not exhibit protective effects in terms of lowering blood pressure levels, reducing organ damage or increasing survival time in hypertensive rats. Conclusion This study suggested that NMN did not demonstrate anti-hypertensive effects in rat hypertension models and could provide valuable insights for future clinical observation on NMN.

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.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.

Objective To investigate the expression of PLCD3 mRNA in the synovium of osteoarthritis(OA)and its relationship with immune cell infiltration.Methods Based on the differentially expressed genes of OA found in the previous study,the expression of phospholipase Cδ3(PLCD3)mRNA was detected by col-lecting synovial samples from OA group and control group.CIBERSORT algorithm was used to analyze the infiltration pattern of immune cells in OA group and control group,and the correlation between PLCD3 and infiltrating immune cells was further analyzed.Results Compared with the control group,the relative expres-sion level of PLCD3 mRNA was significantly increased in synovial samples of OA group(P<0.05).The pro-portions of B cells naive,NK cells activated,M2 macrophages and mast cells activated in synovial tissues of OA group were relatively high(P<0.05).PLCD3 was positively correlated with the proportion of these four immune cells(P<0.05).Conclusion PLCD3 may be a key biomarker for the diagnosis of OA,which may be involved in the pathogenesis of OA by interacting with infiltrating immune cells.

Objective To explore the feasibility and operability in identifying the therapeutic dominant stages of traditional Chinese medicine(TCM)based on subdivision model of disease course.Methods The hierarchical Bayesian model was used to differentiate the disease course of 125 cases of premature ovarian failure(POF),and the disease course of POF were divided into the occult stage,diminished ovarian reserve(DOR)stage,premature ovarian insufficiency(POI)stage,and POF stage.An then the paired sample t-test,Pearson correlation analysis and expert in-depth interview were used for the analysis of the therapeutic effects of TCM for POF at various stages.Results(1)Compared with POF stage,DOR and POI stages were frequently intervened by Chinese patent medicine.(2)In DOR(complicated with POI)stage and POF stage,there was significant difference between the degree of TCM intervention and the therapeutic effect(t =-3.70,P＜0.001).(3)The degree of TCM intervention was positively correlated with treatment outcomes in the DOR stage(r = 0.679,P＜0.001),so did in the POF stage(r = 0.432,P＜0.001),but the correlation in the POF stage was slightly lower than that in the DOR stage.(4)The results of in-depth interviews with experts of TCM gynecology showed that in the concealed phase of POF,the prognosis would be most favorable if TCM regulation and intervention were performed.In the DOR stage and POI stage,treatment with Chinese medicine prescriptions usually brought about better curative effect and prognosis.For the patients at POF stage,the therapeutic effect of TCM depended on the patients'compliance and the treatment course,and the effect was relatively not as good as that of the previous stages.Conclusion In the DOR stage and POF stage,the higher the degree of TCM intervention,the better the prognosis will be achieved for the patients treated with western medicine.In the POF stage,the efficacy of TCM intervention is reduced to a certain extent compared with the DOR stage.The results indicated that it is feasible and operable to identify the TCM therapeutic dominant stages based on the subdivision model of disease course.