A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Objective:To explore the synergistic effect of flumatinib(FLU)combined with histone deacetylase inhibitor chidamide(CHI)and underlying mechanism on Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+ALL)SUP-B15 cells.Methods:CCK-8 method was used to examine the effects of FLU,CHI alone and combination therapy on the proliferation of SUP-B15 cells.Flow cytometry was utilized to analyze the cell cycle and apoptosis.RT-qPCR and Western blot methods were performed to detect target gene expression.Results:FLU combined with CHI significantly inhibited the proliferation,induced G0/G1phase arrest,and increased the apoptosis rate in SUP-B15 cells compared with FLU and CHI alone.The 50 genes were identified by overlapping the two drugs'targets of action with Ph+ALL oncogenic genes in the public databases,and p53 and c-Myc transcription factors and PI3K/AKT signaling pathways were enriched in the overlapped genes.The combination of FLU and CHI significantly reduced the mRNA level of BCR::ABL fusion gene,up-regulated the protein and mRNA levels of p53,BAX,and Caspase-3,and down-regulated the protein and mRNA levels of c-Myc,PIK3CA,PIK3CB,and AKT2 compared with single-drug therapy.The analysis of GEO database and our center cohort showed that c-Myc,PIK3CA,PIK3CB,and AKT2 were significantly up-regulated while p53 was down-regulated in Ph+ALL patients compared to healthy controls.Conclusion:FLU combined with CHI synergistically inhibits cell proliferation,promotes apoptosis,and induces cycle arrest by targeting the PI3K/AKT signaling pathway through the p53/c-Myc axis in Ph+ALL.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

AIM To investigate the mechanism of Shaoyao Gancao Decoction in preventing meglumine diatrizoate-induced post-ERCP pancreatitis in rats through autophagy regulation.METHODS The rats were randomized into the normal group,the model group,the low-dose and high-dose Shaoyao Gancao Decoction(1.5,3.0 g/kg),and the indomethacin suppository group.A rat model of post-ERCP pancreatitis was induced by meglumine diatrizoate injection into the pancreatic duct under continuous pressure.The rats had their pancreatic tissues stained with HE to observe the pathological alterations,inflammatory cell infiltration,hemorrhage and necrosis;their serum levels of IL-1β,IL-6,IL-8,TNF-α,AMS,and IL-10 identified by ELISA;their autophagic vacuoles in pancreatic acinar cells observed by transmission electron microscopy;their pancreatic protein expressions of Beclin1,LC3B,p62,TRAF2 and p-JNK detected by IHC and Western blot;and their pancreatic mRNA expressions of Beclin1 and TRAF2 detected by RT-qPCR.RESULTS Compared with the model group,the high-dose Shaoyao Gancao Decoction group displayed no obvious hemorrhage;improvement in edema of acinar and interstitial cells;obviously less cellular inflammatory infiltration;substantially decreased serum levels of IL-1β,IL-6,TNF-α and AMS(P＜0.05,P＜0.01);drastically reduced amount of autophagosomes in acinar cells;and down-regulated expressions of autophagy-related proteins Beclin1,LC3,p62,TRAF2 and p-JNK(P＜0.05,P＜0.01).CONCLUSION Shaoyao Gancao Decoction can prevent post-ERCP pancreatitis by ameliorating pancreatic tissue injury,decreasing serum inflammatory response level,and interfering with abnormal autophagy of pancreatic acinar cells.Its molecular mechanism may involve inhibition of TRAF2 protein expression and modulation of p-JNK activation.

The aim of this study is to identify the cause of death of a South China tiger cub at the Meihuashan breeding institute of Fujian Province.Pathogenic bacteria were isolated and cultured from liver,spleen,lung and other tissue samples of the dead South China tiger aseptically.The iso-lated bacteria were identified through morphological observation,biochemical characterization,sequence analysis of housekeeping gene gyrB,virulence gene detection,animal pathogenicity test and drug sensitivity test.A pathogenic Aeromonas hydrophila strain,designated FJ/Tiger-201809 was successfully isolated from the trachea of dead South China tiger.The nucleotide sequence ho-mology between the isolate and 11 strains of Aeromonas gyrB ranged from 91.2％to 99.1％,with the highest homology of 99.1％observed with Aeromonas hydrophila(AF208251.1).Genetic evo-lution analysis showed that the isolated strain FJ/Tiger-201809 was in the same evolutionary branch as other reference strains of Aeromonas hydrophila and was closely related.The pathoge-nicity test in mice showed artificial infection of mice with the strain resulted in varying degrees of lesions in several organs of the mice,and the median lethal dose(LD50)was 1 × 107.8 CFU/mL.Virulence gene test results showed that the isolate FJ/Tiger-201809 carried two virulence genes,aer and act.The results of drug sensitivity test showed that FJ/Tiger-201809 was highly sensitive to enrofloxacin and ampicillin among 18 commonly used antibiotics,relatively sensitive to penicil-lin G and doxycycline,and resistant to the other 14 antibiotics.In conclusion,this study isolated and identified a strain of Aeromonas hydrophila from a dead South China tiger with multiple drug resistance and strong pathogenicity,which provided an important reference for the prevention and control of bacterial diseases in South China tiger.

Objective:To investigate the application value of dermoscopy and reflectance confocal microscopy (RCM) in identifying field cancerization in actinic keratosis (AK) in the elderly.Methods:A retrospective analysis was conducted on clinical, dermoscopic, and RCM features of elderly (> 60 years old) patients, who were confirmedly diagnosed with AK and had complete medical records at Shanghai Skin Disease Hospital from January 2022 to December 2023.Results:A total of 132 elderly patients with AK were included. Dermoscopy showed brownish-gray pseudonetwork pigment patterns, follicular horn plugs, irregular branched vessels, and rosette signs in AK lesions. Histopathological examination in 51 patients revealed that 47 (92.16%) were confirmedly diagnosed with AK. Field cancerization was observed in 106 patients (80.3%), among whom 66 (62.26%) had irregular branched vessels, 88 (83.02%) predominantly exhibited brownish-gray pseudonetwork pigment patterns, and 83 (78.30%) showed scattered brown pigment networks/fingerprint-like patterns. Post-treatment follow-up of 63 patients showed varying degrees of changes in vascular and pigment structures by dermoscopy, with significant reductions in follicular horn plugs and superficial yellow-white scales or keratin masses. RCM examinations in 41 AK patients all showed disordered arrangements of keratinocytes presenting as atypical honeycomb patterns, with atypical cells in the AK lesions; in the field cancerization areas of 20 patients, RCM revealed keratinocytes disorderedly arranged in an irregular honeycomb pattern, with some keratinocytes exhibiting mild atypia. Thirty-four AK patients underwent dynamic RCM monitoring before and after 1, 3 and 6 months of ALA-PDT treatment, which showed gradual regularization of arrangements of keratinocytes and reduction of atypical cells, as well as reappearance of atypical keratinocytes upon recurrence.Conclusions:The incidence of field cancerization was relatively high in elderly AK patients. Dermoscopy and RCM are helpful for the early identification of AK and field cancerization, especially in patients with multiple lesions and with difficulties in multi-site biopsy.

Objective To analyze the research hotspots and trends of invasive fungal infections(IFIs)in China over the past 24 years,and provide references and suggestions for future research.Methods Literatures on IFIs re-search in China from 2000 to 2024 were retrieved from China National Knowledge Infrastructure(CNKI)and Web of Science(WOS).CiteSpace software was employed to conduct collaboration network analysis on authors' institu-tions,and co-occurrence,clustering,and burst analyses were conducted on key words.Results A total of 2 479 li-teratures retrieved from CNKI and 1 149 from WOS were included in the analysis,involving 295 research institu-tions,with no core research team identified having a intermediary centrality＞0.1.Institutions with intermediary centrality＞0.1 included Chinese Academy of Sciences,Peking University,Fudan University,Sun Yat-sen Univer-sity and Zhejiang University.Key words with high centrality included"diagnosis""risk factor""voriconazole"and"Candida albicans".Clustering analysis grouped the co-occurrence network of key words into 6 clusters,mainly covering fungal diagnosis,treatment,and susceptible factors.Since 2020,focuses on the safety of antifungal treat-ment agents and primary prevention have emerged,with hot topics including pharmacokinetics,children,clinical features,and risk factors.Conclusion Currently,research teams are dispersed with insufficient interdisciplinary collaboration.Research topics are relatively simple.It is necessary to strengthen research on fungal resistance and healthcare-associated infection prevention and control.Risk factors and prevention measures for IFIs may be the fo-cus of future research.

Objective To analyze the outcome of modified laparoscopic uterosacral fixation in the treatment of anterior and middle pelvic organ prolapse.Methods The clinical data of 30 patients with anterior and middle pelvic organ prolapse undergoing modified laparoscopic uterosacral fixation in our hospital from September 2020 to July 2023 were analyzed retrospectively.The perioperative related indicators and complications of patients during follow-up were observed.The pelvic organ prolapse quantification(POP-Q)scores,pelvic floor distress inventory-short form 20(PFDI-20)scores,pelvic floor impact questionnaire-short form 7(PFIQ-7)scores,and patient global impression of improvement(PGI-I)scores of patients before and after operation were compared.Results The operations of all patients were successfully completed without conversion to open surgery or serious complications.The average operation time was(170.8±21.5)minutes,the average intraoperative blood loss was(29.3±20.2)mL,the average postoperative exhaust time was(1.7±0.7)days,the average postoperative retaining urinal catheter time was(2.3±0.6)days,and the average postoperative hospitalization time was(4.2±0.8)days.Except for the total vaginal length,other indicators of POP-Q of patients 3 and 6 months after operation were significantly improved compared with those before operation(P<0.05).The PFDI-20 score and PFIQ-7 score of patients 6 months after operation were significantly improved compared with those before operation(P<0.05).The objective cure rate of patients was 100%;the results of PGI-I questionnaire showed that the subjective success rate of patients was 100%.Conclusion Modified laparoscopic uterosacral fixation is an effective operation for the treatment of anterior and middle pelvic organ prolapse,which has the advantages of good anatomical recovery,high satisfaction,and few postoperative complications,with a definite short-term curative effect.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.