Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

ObjectiveTo analyze the risk factors for in-hospital mortality in patients with Takotsubo Syndrome （TTS）. MethodsHospitalization data of consecutive patients with TTS from February 2009 to January 2022 were retrospectively collected and analyzed. Patients were divided into survival group and death group according to outcomes. The basic clinical information， triggering factors， laboratory examinations， electrocardiogram， echocardiography， complications and treatments of the two groups were compared. Univariable logistic regression analysis was used to screen the possible risk factors for in-hospital mortality in TTS patients， and multivariable logistic regression analysis was used to determine the independent risk factors for in-hospital mortality in TTS patients. ResultsA total of 62 TTS patients were included in our study， including 21 males （33.9%）， 41 females （66.1%） and 26 postmenopausal women （41.9%）， with the mean age of （55.6±16.2） years， and physical triggers were found in 50 patients （80.6%）. 17 patients （27.4%） died while 45 patients （72.6%） survived during hospitalization. The death group had lower systolic blood pressure and left ventricular ejection fraction （LVEF）， higher incidence rate of syncope， higher level of N-terminal pro-B natriuretic peptide （NT-proBNP） and hypersensitive troponin T （hs TnT） when compared with survival group （all P value <0.05）. As for the triggering factors， the proportion of TTS induced by neurologic disorders in the death group was higher than that in the survival group （P<0.05）. The death group had higher rates of cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， and respiratory failure （all P value <0.05）. Compared with the survival group， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were higher in the death group （all P value <0.05）. Univariable logistic regression analysis suggested that syncope， NT-proBNP， LVEF， neurologic disorders， cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， respiratory failure， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were potential risk factors for in-hospital mortality in TTS patients （all P value <0.05）. Multivariable logistic regression analysis indicated that neurologic disorders ［OR（95%CI）=5.651（1.195，26.715），P=0.029］， atrial fibrillation ［OR（95%CI）=6.217（1.276，30.298）， P=0.024）］ and therapeutic norepinephrin ［OR（95%CI）=8.847（1.912，40.949）， P=0.005］ were independent risk factors for in-hospital mortality in TTS patients. ConclusionsNeurologic disorders， atrial fibrillation and therapeutic norepinephrin are independent risk factors for in-hospital mortality in patients with Takotsubo Syndrome. Clinically， attention should be paid to the prevention and treatment of neurologic disorders and atrial fibrillation； norepinephrine should be carefully used in patients with diagnosed TTS complicated with hemodynamic instability.

In this study, ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography-mass spectrometry(GC-MS) were combined with non-targeted metabonomic analysis based on multivariate statistics analysis, and the content of five indicative components in nardosinone was determined and compared by UPLC. The main chemical components of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma were comprehensively analyzed. The results of multivariate statistical analysis based on liquid chromatography-mass spectrometry(LC-MS) and GC-MS were consistent. G1 and G2 of the imitative wild cultivation group and G8-G19 of the wild group were clustered into category 1, while G7 of the wild group and G3-G6 of the imitative wild cultivation group were clustered into category 2. After removing the outlier data of G1, G2, and G7, G3-G6 of the imitative wild cultivation group were clustered into one category, and G8-G19 of the wild group were clustered into the other category. Twenty-six chemical components were identified according to the positive and negative ion modes detected by LC-MS. The content of five indicative components(VIP>1.5) was determined using UPLC, revealing that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, linarin, nardosinone, and total content in the imitative wild cultivation group were 1.85, 1.52, 1.26, 0.90, 2.93, and 2.56 times those in the wild group, respectively. OPLS-DA based on GC-MS obtained 10 diffe-rential peaks. Among them, the relative content of α-humulene and aristolene in the imitative wild cultivation group were extremely significantly(P<0.01) and significantly(P<0.05) higher than that in the wild group, while the relative content of 7 components such as 5,6-epoxy-3-hydroxy-7-megastigmen-9-one, γ-eudesmol, and juniper camphor and 12-isopropyl-1,5,9-trimethyl-4,8,13-cyclotetrade-catriene-1,3-diol was extremely significantly(P<0.01) and significantly(P<0.05) lower than that in the wild group, respectively. Therefore, the main chemical components of the imitative wild cultivation group and wild group were basically the same. However, the content of non-volatile components in the imitative wild cultivation group was higher than that in the wild group, and the content of some volatile components was opposite. This study provides scientific data for the comprehensive evaluation of the quality of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma.
Gas Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Tandem Mass Spectrometry

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Humans ; Mutation ; NAV1.5 Voltage-Gated Sodium Channel/genetics*

OBJECTIVE: To investigate the effect of exosomal FZD10 derived from non-small cell lung cancer (NSCLC) cells on angiogenesis of human umbilical venous endothelial cells (HUVECs) and explore the possible mechanism. METHODS: We analyzed the expression of FZD10 in two NSCLC cell lines (95D and H1299 cells), normal human bronchial epithelial cells (BEAS-2B cells) and their exosomes isolated by ultracentrifugation. Cultured HUVECs were treated with the exosomes derived from NSCLC cells or NSCLC cells transfected with FZD10-siRNA, and the changes in tube formation ability of the cells were analyzed using an in vitro angiogenesis assay. ELISA was performed to determine the concentration of VEGFA and Ang-1 in the conditioned media of HUVECs, and RT-qPCR was used to analyze the mRNA levels of VEGFA and Ang-1 in the HUVECs. The effects of exosomal FZD10 on the activation of PI3K, Erk1/2 and YAP/TAZ signaling pathways were evaluated using Western blotting. RESULTS: Compared with BEAS-2B cells and their exosomes, 95D and H1299 cells and their exosomes all expressed high levels of FZD10 (P < 0.01). The exosomes derived from 95D and H1299 cells significantly enhanced tube formation ability and increased the expressions of VEGFA and Ang-1 protein and mRNA in HUVECs (P < 0.01), but FZD10 knockdown in 95D and H1299 cells obviously inhibited these effects of the exosomes. Exosomal FZD10 knockdown suppressed the activation of PI3K and Erk1/2 signaling pathways, but had no obvious effect on the activation of YAP/TAZ signaling pathway. CONCLUSION Exosomal FZD10 derived from NSCLC cells promotes HUVEC angiogenesis in vitro, the mechanism of which may involve the activation of PI3K and Erk1/2 signaling pathways.
Carcinoma, Non-Small-Cell Lung/metabolism* ; Cell Proliferation ; Culture Media, Conditioned ; Exosomes ; Frizzled Receptors/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Lung Neoplasms/metabolism* ; MicroRNAs/genetics* ; Neovascularization, Pathologic/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering/metabolism*

OBJECTIVE: To observe the clinical effect of moxibustion with deqi on Alzheimer's disease (AD) rats, and evaluate its effect on β-amyloid (Aβ) transport and enzymatic degradation proteins, to explore its molecular mechanism for improving cognitive function. METHODS: Sixty SPF-grade male SD rats were randomly divided into a blank group (8 rats), a sham-operation group (8 rats) and a model establishment group (44 rats). The rats in the model establishment group were injected with Aβ₁-₄₂ at bilateral ventricles to establish AD model. Among the 38 rats with successful model establishment, 8 rats were randomly selected as the model group, and the remaining rats were treated with mild moxibustion at "Dazhui" (GV 14), once a day, 40 min each time, for 28 days. According to whether deqi appeared and the occurrence time of deqi, the rats were divided into a deqi group (12 rats), a delayed deqi group (10 rats) and a non-deqi group (8 rats). After the intervention, the Morris water maze test was applied to evaluate the cognitive function; the HE staining was applied to observe the brain morphology; the Western blot method was applied to measure the protein expression of Aβ and its receptor mediated transport [low-density lipoprotein receptor-related protein (LRP) 1, receptor for advanced glycation end products (RAGE), apolipoprotein E (ApoE)] and enzymatic degradation [neprilysin (NEP), insulin degrading enzyme (IDE), endothelin converting enzyme (ECE)-1 and angiotensin converting enzyme (ACE) 2]. RESULTS: Compared with the sham-operation group, in the model group, the escape latency was prolonged (P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were reduced (P<0.01); the brain tissue was seriously damaged; the expression of hippocampal Aβ and RAGE was increased (P<0.01), and the expression of hippocampal LRP1, ApoE, NEP, IDE, ECE-1 and ACE2 was decreased (P<0.01). Compared with the model group, the escape latency was shortened in the deqi group (P<0.05, P<0.01), and the escape latency in the delayed deqi group and the non-deqi group was shortened from Day 2 to Day 5 (P<0.05, P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the brain damage in each moxibustion group was reduced, which was smallest in the deqi group, followed by the delayed deqi group and the non-deqi group; the expression of Aβ and RAGE was decreased (P<0.01, P<0.05) and the expression of LRP1 and IDE was increased in each moxibustion group (P<0.01, P<0.05); the expression of ApoE was increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the expression of NEP was increased in deqi group (P<0.05), and the expression of ECE-1 and ACE2 was increased in the deqi group and the delayed deqi group (P<0.05). Compared with the delayed deqi group and the non-deqi group, the escape latency in the deqi group was shortened from Day 3 to Day 5 (P<0.05), and the times of platform crossing and the ratio of platform quadrant to total time were increased (P<0.05, P<0.01). Compared with the non-deqi group, the expression of Aβ was reduced (P<0.05), the expression of LRP1 and ApoE was increased in the deqi group (P<0.05). The expression of NEP in the deqi group was higher than that in the delayed deqi group and the non-deqi group (P<0.05). CONCLUSION Compared with non-deqi, moxibustion with deqi could promote Aβ transport and degradation, thereby reducing Aβ level in the brain and improving cognitive function for AD rats.
Alzheimer Disease/therapy* ; Amyloid beta-Peptides/genetics* ; Angiotensin-Converting Enzyme 2 ; Animals ; Apolipoproteins E/metabolism* ; Hippocampus/metabolism* ; Male ; Moxibustion ; Rats ; Rats, Sprague-Dawley

Aim To analyze the molecular mechanism of rhubarb in the treatment of aeute pancreatitis ( AP) by network pharmacology and molecular docking.Methods TCMSP,TCMID and Swiss target predic¬tion databases were used to screen the active compo¬nents and targets of rhubarb,and genecards and OMIM databases were used to screen the targets of AP.Then the active ingredient drug target network of rhubarb and theactive ingredient disease target network of rhubarb for AP were constructed by using Cytoscape software.PPI network was constructed in string database, and go and KEGG enrichment analysis was performed in metascape database and R language.Finally,molecular docking was used to verify the possibility of binding the core active components to the core target.Results A total of 192 active components and 1 882 AP targets were obtained.The first three active components of rhubarb in the treatment of AP were beta sitosterol, aloe emodin and eupatin.The core target of rhubarb in the treatment of AP was hsp90aal.Go enrichment analysis focused on reaction to toxic substances, while KEGG enrichment analysis was significantly enriched in p53 signaling pathway closely related to AP.Molecular docking showed good binding and stable conformation.Conclusions Rhubarb can affect the expression of AP related genes and proteins through p53 signaling pathway, thereby inhibiting cell apoptosis and allevia¬ting the inflammatory injury of AP.

OBJECTIVE: To observe the therapeutic effect between acupuncture combined with medication and simple medication on migraine and cerebral hemodynamics. METHODS: A total of 120 patients with migraine were randomized into an acupuncture plus medication group (60 cases, 3 cases dropped off) and a medication group (60 cases, 6 cases dropped off). In the medication group, flunarizine hydrochloride capsule was given orally before sleep, 10 mg a day. On the basis of the treatment in the medication group, acupuncture was applied at Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5), Fengchi (GB 20) and etc. in the acupuncture plus medication group, 30 min each time, once a day. Treatment for 4 weeks was required in both groups. Before and after treatment, the visual analogue scale (VAS) score, indexes of cerebral hemodynamic [blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA)] and total TCM syndrome score were observed, and the clinical therapeutic effect and the incidence of the adverse events were evaluated in both groups. RESULTS: Compared before treatment, the VAS scores, the blood flow velocity of ACA, MCA, PCA, VA, BA and the total TCM syndrome scores were decreased in both groups ( CONCLUSION Acupuncture combined with flunarizine hydrochloride capsule can effectively relieve the pain in patients with migraine, reduce the cerebral blood flow velocity, the efficacy is superior to simple flunarizine hydrochloride capsule.
Acupuncture Points ; Acupuncture Therapy ; Hemodynamics ; Humans ; Migraine Disorders/therapy* ; Pain ; Treatment Outcome