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.

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

OBJECTIVES: To systematically evaluate the value of the platelet-to-lymphocyte ratio (PLR) in predicting coronary artery lesions (CAL) in Chinese children with Kawasaki Disease (KD). METHODS: A comprehensive search was conducted in databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database from inception to December 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale, and a Meta analysis was performed using Stata 15.1. RESULTS: A total of ten published reports, involving 3 664 Chinese children with KD, were included in this Meta analysis, of whom 1 328 developed CAL. The Meta analysis revealed a sensitivity of 0.78 (95%CI: 0.71-0.83), specificity of 0.71 (95%CI: 0.61-0.80), overall diagnostic odds ratio of 8.69 (95%CI: 5.02-15.06), and an area under the curve of the summary receiver operating characteristic of 0.82 (95%CI: 0.78-0.85) for PLR in predicting CAL in the children with KD. The sensitivity, specificity, and area under the curve of summary receiver operating characteristic were lower for PLR alone compared to PLR in combination with other indicators. Sensitivity analysis demonstrated the stability of the Meta analysis results with no significant changes upon excluding individual studies. However, a significant publication bias was observed (P<0.001). CONCLUSIONS PLR demonstrates certain predictive value for CAL in Chinese children with KD.
Child ; Humans ; Mucocutaneous Lymph Node Syndrome/pathology* ; Coronary Vessels/pathology* ; Lymphocytes ; Biomarkers ; China ; Coronary Artery Disease/pathology*

Humans ; Lymphoma, Large-Cell, Anaplastic/pathology* ; Receptor Protein-Tyrosine Kinases ; Anaplastic Lymphoma Kinase ; Central Nervous System/pathology*

Male ; Humans ; Prostatic Neoplasms ; Cell Line, Tumor ; Cell Differentiation ; Carcinoma, Neuroendocrine

The causes of constipation are extremely complex and are still not fully clear. In addition to secondary factors such as organic diseases and drugs, constipation may also be related to genetics, diet, intestinal flora, age, gender and so on. At present, according to the etiology, chronic constipation is divided into primary constipation and secondary constipation. However, there are significant differences among current clinical guidelines in the clinical classification of primary constipation. Some guidelines classify primary constipation as slow-transit constipation (STC), outlet obstruction constipation (OOC), and mixed constipation; however, some guidelines classify primary constipation as STC, defecation disorder (DD), mixed constipation, and normal-transit constipation (NTC); what's more, some even propose types which are different from the above sub-types. There are also differences in the understanding of the relationship between functional constipation (FC) and primary constipation and the classification of irritable bowel syndrome predominant constipation (IBS-C) among various clinical guidelines. By reviewing domestic and international guidelines and relevant literature on constipation, the following conclusions are drawn: primary constipation can be divided into IBS-C and FC, and FC can be further divided into STC, OOC, and mixed constipation; primary constipation should not be confused with FC, nor should IBS-C be classified as FC.
Humans ; Irritable Bowel Syndrome/complications* ; Constipation/etiology* ; Gastrointestinal Transit

Objective: To investigate the feasibility and the accuracy of the coronary CT angiography (CCTA)-derived Registry of Crossboss and Hybrid procedures in France, the Netherlands, Belgium and United Kingdom (RECHARGE) score (RECHARGE CCTA) for the prediction of procedural success and 30-minutes guidewire crossing in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Materials and Methods: One hundred and twenty-four consecutive patients (mean age, 54 years; 79% male) with 131 CTO lesions who underwent CCTA before catheter angiography (CA) with CTO-PCI were retrospectively enrolled in this study. The RECHARGE CCTA scores were calculated and compared with RECHARGECA and other CTA-based prediction scores, including Multicenter CTO Registry of Japan (J-CTO), CT Registry of CTO Revascularisation (CT-RECTOR), and Korean Multicenter CTO CT Registry (KCCT) scores. Results: The procedural success rate of the CTO-PCI procedures was 72%, and 61% of cases achieved the 30-minutes wire crossing. No significant difference was observed between the RECHARGE CCTA score and the RECHARGECA score for procedural success (median 2 vs. median 2, p = 0.084). However, the RECHARGE CCTA score was higher than the RECHARGE CA score for the 30-minutes wire crossing (median 2 vs. median 1.5, p = 0.001). The areas under the curve (AUCs) of the RECHARGE CCTA and RECHARGE CA scores for predicting procedural success showed no statistical significance (0.718 vs. 0.757, p = 0.655). The sensitivity, specificity, positive predictive value, and the negative predictive value of the RECHARGE CCTA scores of ≤ 2 for predictive procedural success were 78%, 60%, 43%, and 87%, respectively. The RECHARGE CCTA score showed a discriminative performance that was comparable to those of the other CTA-based prediction scores (AUC = 0.718 vs. 0.665–0.717, all p > 0.05). Conclusion The non-invasive RECHARGE CCTA score performs better than the invasive determination for the prediction of the 30-minutes wire crossing of CTO-PCI. However, the RECHARGECCTA score may not replace other CTA-based prediction scores for predicting CTO-PCI success.

Objective: To investigate the feasibility and the accuracy of the coronary CT angiography (CCTA)-derived Registry of Crossboss and Hybrid procedures in France, the Netherlands, Belgium and United Kingdom (RECHARGE) score (RECHARGE CCTA) for the prediction of procedural success and 30-minutes guidewire crossing in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Materials and Methods: One hundred and twenty-four consecutive patients (mean age, 54 years; 79% male) with 131 CTO lesions who underwent CCTA before catheter angiography (CA) with CTO-PCI were retrospectively enrolled in this study. The RECHARGE CCTA scores were calculated and compared with RECHARGECA and other CTA-based prediction scores, including Multicenter CTO Registry of Japan (J-CTO), CT Registry of CTO Revascularisation (CT-RECTOR), and Korean Multicenter CTO CT Registry (KCCT) scores. Results: The procedural success rate of the CTO-PCI procedures was 72%, and 61% of cases achieved the 30-minutes wire crossing. No significant difference was observed between the RECHARGE CCTA score and the RECHARGECA score for procedural success (median 2 vs. median 2, p = 0.084). However, the RECHARGE CCTA score was higher than the RECHARGE CA score for the 30-minutes wire crossing (median 2 vs. median 1.5, p = 0.001). The areas under the curve (AUCs) of the RECHARGE CCTA and RECHARGE CA scores for predicting procedural success showed no statistical significance (0.718 vs. 0.757, p = 0.655). The sensitivity, specificity, positive predictive value, and the negative predictive value of the RECHARGE CCTA scores of ≤ 2 for predictive procedural success were 78%, 60%, 43%, and 87%, respectively. The RECHARGE CCTA score showed a discriminative performance that was comparable to those of the other CTA-based prediction scores (AUC = 0.718 vs. 0.665–0.717, all p > 0.05). Conclusion The non-invasive RECHARGE CCTA score performs better than the invasive determination for the prediction of the 30-minutes wire crossing of CTO-PCI. However, the RECHARGECCTA score may not replace other CTA-based prediction scores for predicting CTO-PCI success.

OBJECTIVE： To systematically review therapeutic efficacy and safety of mirtazapine combined with selective calcium channel blocker （SCCB） in the treatment of irritable bowel syndrome （IBS）， and provide evidence-based reference for clinical medication. METHODS： Retrieved from the Cochrane Library， PubMed， Embase， Medline， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about mirtazapine combined with SCCB （trial group） versus SCCB （control group） for IBS were collected. After literature screening and data extraction， quality evaluation was performed by using Cochrane system evaluator manual 5.1.0 recommend bias risk evaluation tool. Meta-analysis was performed by using Stata 14.0 software. RESULTS： A total of 14 RCTs involving 1 005 patients were included. The results of Meta-analysis showed that the total response rate [RR＝1.34，95％CI（1.25，1.44），P＜0.001]，neuropeptide-Y level after treatment [SMD＝0.77，95％CI（0.49，1.05），P＜0.001]， response rate of abdominal pain therapy [RR＝1.32，95％CI（1.06，1.66），P＝0.014] and response rate of treatment for abnormal stool characteristics [RR＝1.75，95％CI（1.36，2.27）， P＜0.001] were significantly higher than control group； the scores of depression scale after treatment [SMD＝－1.87， 95％CI （－2.35， －1.39）， P＜0.001]， anxiety scale after treatment [SMD＝－2.25， 95％CI （－3.35， －1.15）， P＜0.001]， abdominal pain symptom score after treatment [SMD＝－7.41， 95％CI  （－8.30，－6.51）， P＜0.001]， diarrhea symptom score after treatment [SMD＝－6.39， 95％CI （－7.96，－4.81）， P＜0.001] were significantly lower than those of the control group. There were no statistical significance in response rate of abdominal distension therapy [RR＝1.07，95％CI（0.90，1.28），P＝0.421] and response rate of abnormal defecation therapy [RR＝1.05，95％CI（0.88，1.26），P＝0.588]， the incidence of abdominal pain [RR＝0.45，95％CI（0.11，1.97）， P＝0.291] and exhaustion [RR＝5.00，95％CI（0.60，41.79），P＝0.137] between 2 groups. CONCLUSIONS： Mirtazapine combined with SCCB can significantly improve therapeutic efficacy of IBS patients， promote clinical symptoms， but do not increase the occurrence of ADR as abdominal pain and exhaustion.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
Antioxidants ; Classification ; Clinical Protocols ; Diagnosis ; DNA ; Embryonic Structures ; Female ; Fertility ; Health Expenditures ; Humans ; Infertility ; Infertility, Male ; Male ; Membranes ; Ovum ; Oxidants ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; Reducing Agents ; Reproductive Health ; Semen ; Spermatozoa ; Subject Headings