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.

Objective: To investigate the morphology and immunohistochemical (IHC) expression of pseudostratified ependymal tubules in ovarian mature teratoma (MT). Methods: Five cases of ovarian MT with pseudostratified ependymal tubules were collected from Shenzhen Hospital(Futian) of Guangzhou University of Chinese Medicine and the Eighth Affiliated Hospital of Sun Yat-sen University from March 2019 to March 2022. In addition, 15 cases of ovarian MT with monolayer ependymal epithelium from Shenzhen Hospital (Futian) of Guangzhou University of Chinese medicine and seven cases of immature teratoma (IMT) from Hainan Provincial People's Hospital from March 2019 to March 2022 were collected as control. The morphologic characteristics and immunophenotypes of pseudostratified ependymal tubules, monolayer ependymal epithelium, and primitive neural epithelial tubules were observed and compared by H&E stain and IHC expression pattern of genes related to the differentiation status of neuroepithelium, namely SALL4, Glypican3, nestin, SOX2, Foxj1, and Ki-67. Results: Mean age of the five patients of ovarian MT with pseudostratified ependymal tubules was 26 years (range from 19 to 31 years). Two tumors were located in the left ovary and three in the right. All five cases were excised, and clinical follow-up was available (mean follow-up 1.5 years; range 0.5 to 3 years). No recurrence was noted in any cases. The pseudostratified ependymal tubules of ovarian MT, which were lined with columnar or oval epithelia up to 4-6 layers, were morphologically similar to the primitive neuroepithelial tubules of IMT and different from monolayer ependymal epithelium of ovarian MT. By immunohistochemistry, SALL4 and Glypican3 were negative, Foxj1 was positive and Ki-67 index was lower in the pseudostratified ependymal tubules and the monolayer ependymal epithelium of ovarian MT. However, the primitive neuroepithelial tubules of IMT showed variably expression of SALL4 and Glypican3, were negative for Foxj1 and high Ki-67 index. All the above three groups expressed nestin and SOX2. Conclusions: The pseudostratified ependymal tubules of ovarian MT, which have morphological similarities to the primitive neuroepithelial tubules of IMT, are similar to the monolayer ependymal epithelia of the MT in immunophenotype. IHC assessment of Foxj1 and Ki-67 is helpful to differentiate the pseudostratified ependymal tubules of ovarian MT from the primitive neuroepithelial tubules of IMT.
Female ; Humans ; Young Adult ; Adult ; Nestin ; Ki-67 Antigen ; Immunohistochemistry ; Ovarian Neoplasms/pathology* ; Teratoma/pathology*

Immunotherapy has opened a new era in cancer treatment. Drugs represented by immune checkpoint inhibitors have led to important breakthroughs in the treatment of various solid tumors, greatly improving the survival rate of cancer patients. Many types of immunotherapeutic drugs have become widely available; however, their efficacy is variable, and relatively few patients with advanced cancer experience life-altering durable survival, reflecting the complex and highly regulated nature of the immune system. The research field of cancer immunotherapy (CIT) still faces many challenges in pursuing the broader social goal of "curing cancer." Increasing attention has been paid to strengthening the understanding of the molecular or cellular drivers of resistance to immunotherapy, actively exploring more effective therapeutic targets, and developing combination therapy strategies. Here, we review the key challenges that have emerged in the era of CIT and the possible solutions or development directions to overcome these difficulties, providing relevant references for basic research and the development of modified clinical treatment regimens.
Combined Modality Therapy ; Humans ; Immunologic Factors ; Immunotherapy ; Neoplasms/therapy*

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

Chronic obstructive pulmonary disease (COPD) has become the third-leading cause of death worldwide, which is a severe economic burden to the healthcare system. Chronic bronchitis is the most common condition that contributes to COPD, both locally and systemically. Neutrophilic inflammation predominates in the COPD airway wall and lumen. Logically, repression of neutrophilia is an essential fashion to COPD treatment. However, currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects. Thus, there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 is a member of the Siglec cell surface immunoglobulin family. It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes. Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils. Furthermore, administration of antibody to Siglec-E, mouse functional ortholog of Siglec-9, restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo. Given the critical role that neutrophils play in chronic bronchitis and emphysema, targeting Siglec-9 could be beneficial for the treatment of COPD, asthma, fibrosis, and related chronic inflammatory lung diseases.
Animals ; Asthma ; Humans ; Lung ; Mice ; N-Acetylneuraminic Acid ; Neutrophils ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Sialic Acid Binding Immunoglobulin-like Lectins

Gout is the second largest metabolic disease in China， which can cause joint tissue damage and a variety of chronic diseases， and seriously affect human life and health. The increase in uric acid caused by disorder of purine metabolism or abnormal uric acid excretion is the biochemical basis of its pathogenesis. Western medical treatment mainly uses anti-inflammatory drugs such as colchicine， non-steroidal anti-inflammatory drugs， and uric acid lowering drugs such as febuxostat and benzbromarone， which have obvious effects， but there are problems such as easy to recurrence after drug withdrawal and more adverse reactions. Traditional Chinese medicine （TCM） has a long history in the treatment of gout， and has the advantages of multi-channel， multi-target， and multi-level symptomatic treatment. It exerts therapeutic effects through lowering uric acid， anti-inflammatory， anti-oxidation， and protecting the kidneys. Its curative effect is obvious and the adverse reaction rate is low. In recent years， there have been many studies on the mechanism of TCM for gout animal models. Based on the review of relevant literature in recent years， this article has systematically sorted out the pathogenesis of gout， the mechanism of TCM for gout and related experimental design. The paper summarized and analyzed the mechanism of TCM in the treatment of gout from the aspects of regulating the level of inflammatory factors， inhibiting oxidation reaction， reducing uric acid and regulating signaling pathway， so as to provide reference for the research and development of drugs for gout.

Literatures on pain intervention with transcutaneous electrical acupoint stimulation (TEAS) were collected by searching the databases both in Chinese and English, and summarized to understand the research progress of TEAS effects on pain mediators in recent years. This will provide a more objective and scientific theoretical basis for clinical practice of TEAS to treat pain syndrome, thus promoting the clinical application of TEAS. Our literature analysis indicated that TEAS effectively regulated the release levels of various pain factors such as prostaglandin, 5-hydroxytryptamine, interleukins, substance P and tumor necrosis factor-α to achieve the analgesic effects by affecting the conduction pathways. TEAS is a safe, non-invasive and effective treatment for pain syndrome. However, further research is necessary due to the lack of rigor of the current clinical trial design.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.
Adenocarcinoma of Lung/genetics* ; Circulating Tumor DNA/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Protein Kinase Inhibitors

BACKGROUND: Numerous clinical data have shown that electro-acupuncture in the treatment of knee osteoarthritis has the advantages of fast onset, good therapeutic effect and less side effects, but there is a lack of multicenter large-sample clinical research regarding the treatment of knee osteoarthritis. OBJECTIVE: To systematically evaluate the effect of electro-acupuncture on pain relief and joint function in patients with knee osteoarthritis by meta-analysis. METHODS: The literatures related to clinical randomized controlled trials of electro-acupuncture treatment of knee osteoarthritis were retrieved in CNKI, Wanfang, VIP, PubMed, Embase and Cochrance Library database from the inception to June 2019. After literature screening, a meta-analysis of included studies was carried out using Review Manager 5.3. RESULTS AND CONCLUSION: Finally, 11 articles were included in the study, with 721 cases of knee osteoarthritis. There were 366 cases in the electro-acupuncture group and 361 in the control group with routine acupuncture or drug treatment. Compared with the control group, the total effective rate, cure rate, visual analogue scale score, WOMAC score and ISOA score in the electro-acupuncture group were significantly higher than those in the control group [odds ratio (OR)=3.22, 95% confidence interval (CI)(2.13, 4.87), Z=5.53, P < 0.000 01; OR=2.73, 95%CI(1.80, 4.15), Z=4.72, P < 0.000 01; mean difference (MD)=-1.00, 95%CI(-1.71, -0.30), Z=2.80, P=0.005; MD=-7.69, 95%CI(-10.31, -5.07), Z=5.75, P < 0.000 01; MD=-2.22, 95%CI(-3.74, -0.70), Z=2.86, P=0.004]. Based on the evidence of meta-analysis, the short-term effect of electro-acupuncture on knee osteoarthritis is definite, and electro-acupuncture can play a positive effect on pain symptoms and joint function of knee osteoarthritis patients with few adverse reactions. Considering small sample size, low-quality literatures and possible presence of bias factors, further investigations on more high-quality randomized controlled trials are warranted.

Objective:The aim of this study was to research the relationship between HPLC fingerprint and anti-inflammatory effect of Zhideke granules， and the substance basis of its anti-inflammatory effect was preliminary explored. Method:The fingerprint of 10 batches of Zhideke granules were determined by HPLC， the mobile phase was consisted of methanol-0.2% phosphoric acid solution for gradient elution with a detection wavelength of 254 nm. Similarity analysis， hierarchical cluster analysis （HCA）， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to evaluate the quality difference between batches of Zhideke granules. The correlation analysis between the common peaks and the inhibition rates of Zhideke granules on ear swelling and cotton ball granuloma in mice was carried out by partial least squares （PLS）， and the peaks greatly contributing to the anti-inflammatory effect were screened out. Result:There were 31 common peaks in the HPLC fingerprint of Zhideke granules. The similarities of 10 batches samples were ≥0.992. The HCA and PCA analysis results were consistent， and the samples were divided into 3 categories. Combined with the OPLS-DA results， 15 components were the main markers affecting the differences of different batches of samples. Different batches of Zhideke granules differed in anti-inflammatory effect. The chromatographic peaks being positively correlated with the anti-inflammatory effect were mainly from Belamcandae Rhizoma and Scutellariae Radix， Chromatographic peaks 3， 6， 19， 27-30 had significant contribution to anti-inflammatory effect， of which peaks 28 and 30 were irisflorentin and wogonin. Conclusion:HPLC fingerprint combined with chemical pattern recognition method can provide a reference for systematic evaluation of the overall quality of Zhideke granules. Zhideke granules has a certain inhibitory effect on acute and chronic inflammation in mice， and the anti-inflammatory effect is the result of the combined action of various ingredients， while Belamcandae Rhizoma and Scutellariae Radix have significant significance for the anti-inflammatory effect.