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 effects of long-term and low dose ionizing radiation on ocular lens opacities of residents living in areas with high natural radiation background(HNRB) in Yangjiang City, China. METHODS: A total of 483 Han residents from Yangjiang City(HNRB area) and 517 from Enping City(control area) were selected as study subjects using a cluster random sampling method. Questionnaire survey and lens examination were carried out. The risk factors of lens opacity and its severity were analyzed by logistic regression analysis. RESULTS: The prevalence rates of lens opacity, cortical opacity and posterior subcapsular opacity in HNRB area were higher than those in control area(60.7% vs 51.6%, 53.4% vs 46.8%, 21.9% vs 9.3%, all P<0.05). There was no significant difference in karyotype turbidity between HNRB area and control area(52.4% vs 47.6%, P>0.05). After adjusting for confounding factors including age, gender, cardiovascular/metabolic diseases, smoking, alcohol drinking and tea drinking, the unconditional logistic regression analysis results showed that the risk of ocular opacity, cortical opacity and posterior subcapsular opacity in residents of HNRB area was higher than that in control area(all P<0.05). Multivariate disordered logistic regression analysis results showed that residents in the HNRB area had a higher risk of grade two karyotype turbidity than grade one karyotype turbidity(P<0.01). Ordered logistic regression analysis results showed that residents in HNRB area had an increased risk of developing severe cortical turbidity(P<0.01). CONCLUSION: Long-term and low dose ionizing radiation exposure may increase the risk of ocular lens opacity, especially cortical and posterior subcapsular cataract, and affect the severity of the disease.

Background: Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles. Methods: A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC. Results: The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. Conclusions Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

OBJECTIVETo study the inhibition of berberine (BBR) against ECV-304 apoptosis induced by Staphylococcus aureus (S. aureus).

METHODSECV-304 cells were pre-treated with 128 microg/mL BBR for 2 h and then S. aureus was added (1:100). The viability of cells was detected by MTT (3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The morphological changes were observed by Hoechst 33258 staining. The protection of BBR for infected cells was detected by DNA Ladder.

RESULTSECV-304 cells' viability were not obviously affected by berberine. But S. aureus induced ECV-304 cells' viability could be significantly inhibited by pre-treatment of BBR (P < 0.05). Besides S. aureus-induced ECV-304 apoptosis could be reduced, with significantly lessened apoptotic body and unobvious DNA degradation.

CONCLUSIONBBR could significantly inhibit S. aureus induced ECV-304 apoptosis.

Apoptosis ; drug effects ; Berberine ; pharmacology ; Cell Line ; Human Umbilical Vein Endothelial Cells ; drug effects ; microbiology ; pathology ; Humans ; Staphylococcus aureus

OBJECTIVETo compare the treatment results of three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (2D) for patients with locally advanced non-small-cell lung cancer (NSCLC).

METHODSFive hundred and twenty seven patients with stage III NSCLC treated between Jan 2000 and Dec 2006 were included in this study. Among them, 253 cases were treated with 3D-CRT, and 274 with conventional radiotherapy. In the 3D group, 159 (62.8%) patients received chemoradiotherapy, 77 with total radiotherapy dose of > 60 Gy, 49 with 50 - 60 Gy. In the 2D group, 127 (46.4%) patients received chemoradiotherapy, 48 with total radiotherapy dose of > 60 Gy, 75 with 50 - 60 Gy.

RESULTSThe 1-, 3-, 5-year overall survival rates (OS) and median survival time for patients treated with 3D-CRT were 73.3%, 26.1%, 14.4% and 20.1 months, respectively, and that of patients treated with 2D radiotherapy were 61.0%, 13.8%, 8.0% and 15.6 months, respectively (P = 0.002). The 1-, 3-, 5-year cause-specific survival rates (CSS) were 79.0%, 33.3%, and 20.8% for the 3D group and 65.1%, 16.7%, 11.2%, respectively, for the 2D group (P = 0.000). The 1-, 3-, and 5-year locoregional control rates were 71.6%, 34.3% and 31.0% for patients treated with 3D radiotherapy and 57.3%, 22.1% and 19.2%, respectively, for patients treated with 2D treatment (P = 0.002). The results of multivariate analysis showed that 3D-CRT, KPS, clinical tumor response and pretreatment hemoglobin level were independently associated with increased OS and CSS. No statistically significant differences were found between the radiation complications in the two groups.

CONCLUSIONSThe results of our study demonstrate that 3D-conformal radiotherapy improves the survival rate in patients with stage III NSCLC compared with that of 2D radiation therapy.

Aged ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; Chemoradiotherapy ; Female ; Follow-Up Studies ; Hemoglobins ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; Male ; Neoplasm Staging ; Radiation Pneumonitis ; etiology ; Radiotherapy Dosage ; Radiotherapy, Conformal ; adverse effects ; methods ; Survival Rate

China ; epidemiology ; Dengue ; epidemiology ; virology ; Dengue Virus ; classification ; genetics ; Genome, Viral ; Open Reading Frames ; Phylogeny ; Viral Nonstructural Proteins ; genetics

OBJECTIVETo investigate the association between survival and postoperative three-dimensional conformal radiotherapy (3DCRT) in patients with resected non-small cell lung cancer (NSCLC).

METHODSEighty-four patients were treated with surgery and postoperative 3DCRT for NSCLC. Sixty-five (77.4%) patients received lobectomy, and 19 (22.6%) received pneumonectomy. Fifty-four (64.3%) patients achieved R0 resection and 30 cases (35.8%) received R1/R2 resection. Fifty-two patients were of stage IIIA and 24 patients were of stage IIIB. Photon energy of 6 MV was used for all the patients. The median 3DCRT dose was 60 Gy (40 - 70 Gy) with a fraction size of 2 Gy. Thirty-seven patients received median 3 cycles of adjuvant chemotherapy. The median follow-up was 35.5 months for survivors.

RESULTSThe overall 3-year survival rate was 58.6%, and the 4-year overall survival rate was 43.9%. Of the 43 patients who had treatment failure, only 8 (9.9%) patients showed intrathoracic recurrence, but 38 (46.9%) patients had distant metastasis. The univariate analysis for all patients showed that sex, age, weight loss, tumor size, pathology and stage were not correlated with prognosis. R1/R2 resection was associated with a significantly worse survival. Toxicities were acceptable, with 9 (11.1%) patients appeared higher than NCI CTC grade 2 radiation pneumonitis.

CONCLUSIONIn a population-based cohort, postoperative 3DCRT for NSCLC provides a good prognosis, and the radiation-related pneumonitis is acceptable.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Imaging, Three-Dimensional ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Pneumonectomy ; methods ; Radiation Pneumonitis ; etiology ; Radiotherapy Dosage ; Radiotherapy, Conformal ; adverse effects ; methods ; Radiotherapy, High-Energy ; adverse effects ; Survival Rate

BACKGROUNDBeta(2)-adrenoceptor (beta(2)AR) desensitization is a common problem in clinical practice. beta(2)AR desensitization proceeds by at least such three mechanisms as heterologous desensitization, homologous desensitization and a kind of agonist-induced rapid phosphorylation by a variety of serine/threonine kinases. It is not clear whether there are other mechanisms. This study aimed to investigate potential mechanisms of beta(2)AR desensitization.

METHODSTwenty-four BALB/c (6-8 weeks old) mice were divided into three groups, which is, group A, phosphate buffered saline (PBS)-treated; group B, ovalbumin (OVA)-induced; and group C, salbutamol-treated. Inflammatory cell counts, cytokine concentrations of bronchoalveolar lavage fluid (BALF), pathological sections, total serum IgE, airway responsiveness, membrane receptor numbers and total amount of beta(2)AR were observed. Asthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were established. Groups B and C were selected for two-dimensional gel electrophoresis (2DE) analysis so as to find key protein spots related to beta(2)AR desensitization.

RESULTSAsthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were verified by inflammatory cell count, cytokine concentration of BALF, serum IgE level, airway hyperreactivity measurement, radioligand receptor binding assay, Western blot analysis, and pathologic examination. Then the two groups (groups B and C) were subjected to 2DE. Two key protein spots associated with beta(2)AR desensitization, Rho GDP-dissociation inhibitor 2 (RhoGDI(2)) and peroxiredoxin 5, were found by comparative proteomics (2DE and mass spectrum analysis).

CONCLUSIONOxidative stress and small G protein regulators may play an important role in the process of beta(2)AR desensitization.

Albuterol ; therapeutic use ; Animals ; Asthma ; drug therapy ; metabolism ; Disease Models, Animal ; Electrophoresis, Gel, Two-Dimensional ; Female ; Guanine Nucleotide Dissociation Inhibitors ; analysis ; Lung ; chemistry ; pathology ; Mice ; Mice, Inbred BALB C ; Oxidative Stress ; Peroxiredoxins ; analysis ; Proteomics ; Receptors, Adrenergic, beta-2 ; physiology ; rho-Specific Guanine Nucleotide Dissociation Inhibitors

BACKGROUNDCD4(+)CD25(+) regulatory T cells (Tregs) mediate immune suppression through cell-cell contact with surface molecules, particularly cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), and transforming growth factor beta (TGF-beta), but little is known about the exact role of Tregs in the pathogenesis of asthma. This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells-derived Tregs in patients with atopic asthma and healthy subjects, and to investigate the effect of inhaled corticosteroid on them.

METHODSThe expression of surface molecules on CD4(+)CD25(high) Tregs was detected by flow cytometry. The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro. Total serum immunoglobulin E (IgE) and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay, respectively.

RESULTSEquivalent numbers of peripheral Tregs were found in patients with atopic asthma (stable and acute) and healthy subjects. Tregs preferentially expressed CTLA-4, GITR, toll-like receptor 4 (TLR4), latency-associated peptide (LAP/TGF-beta1), and forkhead box P3 (FOXP3). Patients with acute asthma had decreased numbers of CD4(+)CD25(high)LAP(+) T cells compared to healthy subjects and stable asthmatics. Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently. Furthermore, the percentages of Tregs expressing LAP were negatively correlated with total serum IgE levels and severity of asthma, but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma.

CONCLUSIONSThe results suggest that membrane-bound TGF-beta1 is a potential candidate for predicting the severity of asthma, and may contribute to the sustained remission of asthma. Strategies targeting Tregs on their surface markers, especially TGF-beta1, are promising for future therapy of asthma.

Administration, Inhalation ; Adrenal Cortex Hormones ; administration & dosage ; Adult ; Antigens, CD ; blood ; Antigens, Differentiation ; blood ; Asthma ; drug therapy ; immunology ; Budesonide ; pharmacology ; CTLA-4 Antigen ; Female ; Forkhead Transcription Factors ; blood ; Glucocorticoid-Induced TNFR-Related Protein ; Humans ; Male ; Middle Aged ; Receptors, Nerve Growth Factor ; blood ; Receptors, Tumor Necrosis Factor ; blood ; T-Lymphocytes, Regulatory ; drug effects ; immunology ; Toll-Like Receptor 4 ; blood ; Transforming Growth Factor beta1 ; blood

OBJECTIVETo summarize our experience and evaluate the prognostic factors of locally advanced non small cell lung cancer (LA-NSCLC) treated with three dimentional conformal radiotherapy (3D-CRT).

METHODS118 patients with stage IIImA/IIIB non small cell lung cancer were treated with 3D-CRT from Nov. 2001 to Mar. 2005. 113 patients with complete clinical data were eligible for analysis, 45 of them received radiotherapy alone; 39 were treated by concurrent chemoradiation with paclitaxol plus carboplatin in 32 patients and topotecan in 7 patients, and 29 by sequential chemoradiation with platinum-based regiment in most of them. The dose of radiation for the thoracic field ranged from 26 Gy to 75 Gy with a median dose of 60 Gy. GTV and PTV were collected from the 3D treatment plans in 79 and 101 patients, respectively. Overall survival (OS) was calculated using the Kaplan-Meier method. Comparisons among the curves were made using a two-tailed long-rank test. The Cox model was used for multivariate analysis.

RESULTSThe 1-, 2- and 3-year overall survival rate was 60.7%, 31.6% and 22.4%, respectively, with a median survival time of 17 months. In univariate analysis, the following characteristics were significantly associated with longer survival: absence of chest pain, good karnofsky performance status (KPS), albumin > 4.2 g/L, hemoglobin > or = 140 g/L (male) or 130 g/L (female), response to radiotherapy and GTV < 100 cm3. However, multivariate analysis revealed that only good KPS was an independent risk factor predicting the survival.

CONCLUSIONThree-dimensional conformal radiotherapy is effective in the treatment of locally advanced non-small cell lung cancer with acceptable complications. Karnofsky performance status is the only independent prognositic factor.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Brain Neoplasms ; secondary ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; secondary ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Karnofsky Performance Status ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Particle Accelerators ; Proportional Hazards Models ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; methods ; Radiotherapy, Conformal ; methods ; Remission Induction ; Survival Rate