Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

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 investigate the effects and mechanisms of fatty acid binding protein 4(FABP4)on ferroptosis in human renal tubular epithelial cells(HK-2)treated with hypoxia/reoxygenation(H/R).Methods HK-2 cells were cultured in vitro and subjected to hypoxia for 24 hours followed by reoxygenation for different durations(1,3,6 h).The messenger RNA(mRNA)and protein levels of FABP4 in HK-2 cells were detected at each time point using real-time fluorescent quantitative polymerase chain reaction and Western blotting.Small interfering RNA(siRNA)technology was used to silence the expression of FABP4 gene in HK-2 cells,which were then treated with H/R(24 h of hypoxia and 6 h of reoxygenation)or treated with the Nrf2 inhibitor ML385.Cell proliferation activity was assessed using cell counting kit-8(CCK-8).Lactate dehydrogenase(LDH)levels were measured by enzyme-linked immune absorbent assay.Malondialdehyde(MDA),glutathione(GSH)and ferrous ion(Fe2+)levels were determined by biochemical technology.Reactive oxygen species(ROS)levels were detected using the 2',7'-dichlorodihydrofluorescein diacetate fluorescence probe.Protein expression levels of FABP4,nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were measured by Western blotting.Results The mRNA and protein levels of FABP4 in HK-2 cells increased with prolonged reoxygenation time(all P<0.05).H/R treatment reduced cell proliferation activity,increased LDH levels in the cell supernatant,and elevated MDA,Fe2+and ROS levels in HK-2 cells while decreasing GSH levels and the protein levels of Nrf2,HO-1,GPX4 and SLC7A11(all P<0.05).Silencing FABP4 enhanced the proliferation activity of H/R-treated HK-2 cells(P<0.05),reduced MDA,Fe2+and ROS levels,increased GSH levels,and elevated the protein levels of Nrf2,HO-1,GPX4 and SLC7A11(all P<0.05).However,these beneficial effects of FABP4 silencing on H/R-induced ferroptosis in HK-2 cells were reversed by co-treatment with ML385.Conclusions Silencing FABP4 alleviated H/R-induced ferroptosis in HK-2 cells,possibly by activating the Nrf2/GPX4 axis.

Objective The biological characteristics and action mechanisms underlying the excellent performance of skeletal muscles were studied through experiments to provide a scientific basis for the development of flexible actuators with performance comparable to that of skeletal muscles.Methods A frog skeletal muscle sample was contracted by applying electrical stimulation,and then tensile load was applied to it to analyze the relationship between the driving properties(such as contraction length and output force)of skeletal muscle and its structure from three aspects:skeletal muscle dimensions,tendon,and epimysium.Results The contraction lengths of these skeletal muscle samples were approximately 28.92％and 20％under unloaded conditions and under 50％of their maximum output force,respectively.When the load on the skeletal muscles did not exceed 20％of their maximum output force,they also exhibited the property of rapid reduction(approximately 1.25 s).The active tendon increased contraction by approximately 19.68％compared with the inactive tendon,and the integrity of the epimysium protected the force transfer efficiency of skeletal muscles.Conclusions By simulating the structural and biomechanical properties of skeletal muscles,flexible actuators can achieve better driving performance,thus greatly promoting the development of bionic robots.

Purpose To analyze the sonographic features of incarcerated gravid uterus and evaluate the diagnostic value of ultrasonography.Materials and Methods Clinical data of eight patients diagnosed with incarcerated gravid uterus at Sichuan Provincial Maternity and Child Health Care Hospital from January 2018 to December 2023 were retrospectively analyzed.Clinical manifestations,sonographic characteristics,management approaches and pregnancy outcomes were evaluated.Results Among the eight confirmed cases,seven presented with initial symptoms of dysuria and urinary retention,while one reported irregular lower abdominal pain.Ultrasonography consistently demonstrated:retroverted and retroflexed uterine position with the uterine body posterior to the cervix.Elongated cervix(range:4.0-8.6 cm)displaced anteriorly.Overdistended,elongated and superiorly displaced bladder in seven cases.Management included successful manual reduction via knee-chest position after catheterization in seven patients.One patient was managed conservatively with close monitoring and delivered by cesarean section at term.All eight patients achieved successful term deliveries with favorable maternal and neonatal outcomes.Conclusion Prenatal ultrasonography plays a crucial role in diagnosing and managing incarcerated gravid uterus.Early recognition of characteristic sonographic features facilitates prompt diagnosis and intervention,thereby mitigating risks of adverse pregnancy outcomes.

Objective To identify the potential pathological mechanisms of tuberculous spondylitis(TS).Methods Spinal specimens were collected from 13 TS patients and 13 controls who received treatment at a hospital from March 2021 to March 2023.Specimens were randomly selected from 3 TS patients and 3 controls to perform high-throughput lncRNAs and mRNAs sequencing with Illumina NovaSeq 6000.Differentially expressed lncRNAs(DELncRs)and mRNAs(DEmRs)in TS specimens were identified and analyzed through differential expression,and enrichment analysis was performed.The top 20 DEmRs with high connectivity were identified through protein-protein interaction(PPI)network.Regulatory network of DElncRs and DEmRs was built.Finally,gene expression of the remaining specimens was analyzed using qRT-PCR detection.Results A total of 1 243 DEmRs and 262 DElncRs were identified.Enrichment analysis revealed that muscle contraction,muscle system processes,muscle structural development,PI3K Akt signaling pathway,calcium signaling pathway,and cAMP signaling pathway were activated in TS,while responses to cytokines,cytokine-mediated signaling pathways,regulation of immune system processes,cytokine-cytokine receptor interactions,human T-cell leukemia virus type 1 infection,and phago-somes were inhibited in TS.Three sub-networks were identified in PPI,among which MYL1,TTN,LOC102723407,HLA-A,interleukin(IL)-6,and IL-1β had the highest connectivity and were identified as key DEmRs.MYL1,TTN,and IL-6 were regulated by DElncRs.qRT-PCR validated the differential expression of key DEmRs in TS.Conclusion DEmRs are regulated by lncRNAs and participate in the pathological process of TS,and the immune responses are inhibited in diseases condition.This study reveals key molecules and signaling pathways in TS,providing new insights into the pathological mechanisms of TS,and suggest scientific basis for developing new therapeutic targets.

Objective To study the relationship between the mandibular bone arch and the dental arch in patients with skeletal Class Ⅱ malocclusion and compare it with the Class Imalocclusion by establishing a 3D digital model.Methods A total of 25 cases with skeletal Class Ⅱ malocclusion and 25 cases with skeletal Class Ⅰ normal occlusion were selected.The mandibular model was scanned and a three-dimensional digital model was set up.After the determination of the WALA ridge and the FA point,the reference plane and coordinate system was established.Four degree polynomial curve fitting was performed with WALA ridge and FA point coordinates to re-present the corresponding basal and dental arch curves.The width difference between the basal arch curve and the dental arch curve was measured and calculated at 3 mm,10 mm,and 18 mm away from the horizontal axis of the coordinate.The differences of basal bone and dental arch width between skeletal Class Ⅱ and skeletal Class Ⅰ malocclusion was compared.Results The width differences be-tween the arch and the dental arch in the anterior,middle and posterior mandibular segments of skeletal Class Ⅱ patients were-1.58 mm,1.80 mm and 3.80 mm,respectively.The width differences between the arch and the dental arch in the anterior,middle and pos-terior mandibular segments of skeletal Class Ⅰ patients were 2.08 mm,2.92 mm and 4.24 mm,respectively.There was a significant difference between skeletal Class Ⅱ and skeletal Class Ⅰ in the anterior and middle segments(P＜0.05),but no significant difference in the posterior segment(P＞0.05).Conclusion In skeletal Class Ⅰ patients,the width of the basal bone is larger than that of the dental arch,and the dental arch was located medial to the basal bone.In skeletal Class Ⅱ patients,the width of the anterior arch is larger than the width of the basal bone,that is,the dental arch is located outside the basal bone.The width difference of the basal arch in skeletal Class Ⅱ is smaller than that in skeletal Class Ⅰ.

Amorphous calcium phosphate（ACP）is a component of urinary stones，primarily forming mixed stones with calcium oxalate，while pure ACP stones are relatively rare. This article reports a case of a patient with an ACP bladder stone who was admitted due to progressive dysuria over 5 years，which had worsened in the past months. Upon admission，tPSA was 29.63 ng/ml. CT and enhanced MRI revealed multiple bladder stones and prostatic hyperplasia. The patient underwent ultrasound-guided prostate biopsy and transurethral cystolithotripsy with pneumatic lithotripsy. Postoperative infrared spectroscopy confirmed the stone composition as ACP，and prostatic adenocarcinoma was diagnosed by prostate biopsy pathology. Endocrine therapy was administered postoperatively，and follow-up imaging at 3 months showed no stone. This article presents the first reported case of an ACP bladder stone coexisting with prostate cancer，providing important clinical insights into the etiology of such stones and the rare local manifestations of prostate cancer.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

The prevalence of obesity is continuously increasing worldwide, making it a major global health issue that impacts public health and places a growing burden on healthcare systems. Bariatric metabolic surgery, currently the most effective treatment for weight loss and improving obesity-related metabolic diseases, still has significant limitations in patient selection, personalized surgical planning, and accurate prediction of postoperative complications and weight loss outcomes. With the rapid advancement of artificial intelligence (AI) technology, the diagnostic and therapeutic paradigm of bariatric and metabolic surgery is expected to undergo revolutionary improvement. The authors explore the latest applications of AI in bariatric and metabolic surgery, including surgical training, preoperative diagnosis and formulation of treatment strategy, intra-operative assistance, as well as prediction of related risks and weight loss effects after surgery. It aims to provide valuable insights for clinical practice, facilitating the evolution of bariatric and metabolic surgery toward greater precision, efficiency, and personalization.