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.

ObjectiveTo investigate the therapeutic effects and mechanisms of modified Huangqi Jianzhong decoction （HQJZ） on gastric precancerous conditions （GPC）. MethodsIn the cell experiment， human gastric mucosal epithelial cells underwent malignant transformation induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPC （MC cells）. The cells were allocated into four groups： control ， model， low-dose HQJZ （HQJZ-L）， and high-dose HQJZ （HQJZ-H）. The control and model groups were cultured with the complete medium， while HQJZ-L and HQJZ-H groups received additional interventions with HQJZ at low （0.5 g·L^-1） and high （1.0 g·L^-1） doses， respectively. Cell counting kit-8 （CCK-8） assay was used to evaluate cytotoxicity， Transwell assay to assess cell invasion， Annexin V-FITC/PI staining to detect apoptosis， immunofluorescence assay to analyze reactive oxygen species （ROS） expression and mitochondrial autophagy， and Western blot to verify expression of proteins in key pathways. In the animal experiment， the GPC model was established in healthy BALB/c mice through MNNG induction. Twenty-four mice were allocated into four groups： control， model， HQJZ-L， and HQJZ-H. Control and model groups received normal saline （10 mL·kg^-1·d^-1） orally， while HQJZ-L and HQJZ-H groups were administrated with low-dose （6.24 g·kg^-1·d^-1） and high-dose （12.48 g·kg^-1·d^-1） HQJZ， respectively. After treatment， hematoxylin‑eosin （HE） staining and AB-PAS staining were performed to observe histopathological changes in the gastric tissue. Immunofluorescence assay was used to detect reactive oxygen species （ROS） and microtubule-associated protein 1 light chain 3 （LC3） levels in the gastric mucosa， TdT-mediated dUTP nick-end labeling （TUNEL） staining to assess apoptosis rates， and Western blotting and immunohistochemistry （IHC） to analyze the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， and foxhead box O3 （FoxO3）. ResultsCell viability assays showed that HQJZ dose-dependently reduced MC cell viability compared with the control group （P<0.05， P<0.01）. Transwell assays revealed that the model group exhibited enhanced cell invasion compared with the control group （P<0.05）. Compared with the model group， HQJZ treatment attenuated the cell invasion （P<0.05）. Gastric mucosal pathology in mice demonstrated that compared with the control group， the model group showed elevated HE and AB-PAS pathological scores （P<0.05）， while HQJZ treatment reduced these scores （P<0.05）. Transmission electron microscopy revealed increased mitochondrial number and volume in the model group compared with the control group. HQJZ treatment resulted in abnormal mitochondrial structure and significant alterations in rough endoplasmic reticulum morphology and distribution， presenting as dilated and hollow forms. Mitochondrial and apoptosis assessments indicated that compared with the control group， the model group exhibited enhanced Mito Tracker Green fluorescence （P<0.05）， no significant change in DCFH-DA fluorescence， Mito Tracker Red CMXRos fluorescence， ROS immunofluorescence， or malondialdehyde （MDA） level， increased GSH level （P<0.05）， enhanced LC3 fluorescence （P<0.05）， no significant change in apoptosis rate， and elevated ATP content in cells and mouse serum （P<0.05）. Compared with the model group， HQJZ treatment reduced Mito Tracker Green fluorescence （P<0.05）， increased DCFH-DA fluorescence， Mito Tracker Red fluorescence， MDA level， LC3 fluorescence， and apoptosis rate （P<0.05）， and decreased cellular ATP content （P<0.05）. The HQJZ-L group showed no significant change in ROS immunofluorescence or GSH level， whereas the HQJZ-H group demonstrated enhanced ROS immunofluorescence and glutathione （GSH） level （P<0.05）. Immunohistochemistry and Western blotting revealed that compared with the control group， the model group exhibited increased numbers of PCNA- and Ki67-positive cells （P<0.05） and elevated protein levels of FoxO3， sirtuin 1 （SIRT1）， and B-cell lymphoma 6 （Bcl-6） （P<0.05）. HQJZ treatment reduced the numbers of PCNA- and Ki67-positive cells （P<0.05） and lowered the protein levels of FoxO3， SIRT1， and Bcl-6 （P<0.05）. ConclusionHQJZ alleviates the progression of gastric precancerous lesions by regulating mitochondrial function via the FoxO3/ROS pathway and promoting apoptosis of GPC-malignant cells.

Renal fibrosis is the common pathological endpoint of many forms of chronic kidney disease (CKD), yet the mechanisms determining effective repair versus persistent fibrotic remodeling remain incompletely understood. Peritubular capillaries (PTCs) are not merely passive targets of fibrotic injury, but form a dynamic vascular microenvironment linking regional perfusion, oxygen delivery, tubular metabolism, endothelial barrier integrity, pericyte support, immune-cell trafficking, and extracellular matrix (ECM) remodeling. We propose that PTC abnormalities should not be interpreted simply as reduced capillary density, but as a multidimensional disturbance of microvascular structure and function. Structural vascular preservation does not necessarily indicate effective microcirculation: anatomically detectable capillaries may still exhibit impaired perfusion, barrier dysfunction, abnormal endothelial-pericyte interactions, disturbed oxygen metabolism, or reduced network connectivity. Conversely, increased angiogenesis does not necessarily signify successful vascular repair if vessels remain immature, poorly perfused, or inadequately integrated into the existing network. To organize these abnormalities, we conceptualize PTC remodeling into four predominant but nonexclusive states: endothelial barrier disruption with inflammatory adhesion; endothelial-pericyte uncoupling with no-reflow; dysregulated angiogenesis with network simplification; and capillary rarefaction with fibrotic matrix locking. These states are not sequential stages of CKD. They may coexist within the same kidney, overlap within the same anatomical region, and vary with disease etiology, injury phase, vascular compartment, and treatment exposure. We further propose six dimensions for evaluating PTC status—structural presence, functional perfusion, barrier integrity, pericyte coupling, oxygen metabolism, and network connectivity—so that vascular quantity, function, and reparative capacity are assessed separately rather than inferred from a single endothelial marker or capillary-density measurement. Mechanistically, these states converge on a bidirectional microvascular-fibrotic feedback loop. Barrier disruption facilitates leukocyte recruitment and alters vascular paracrine signaling. Endothelial-pericyte uncoupling compromises capillary stability, whereas abnormal pericyte contraction may increase local vascular resistance and contribute to no-reflow before overt capillary loss. Dysregulated angiogenesis may generate vessels that fail to mature or connect to an effective perfusion network. Progressive capillary rarefaction compromises oxygen delivery, while sustained tubular transport demand and mitochondrial dysfunction may aggravate regional oxygen supply-demand mismatch. Injured tubules, immune cells, endothelial cells, pericytes, and fibroblasts communicate through soluble mediators, extracellular vesicles, direct cell contact, and cell-matrix signaling. Importantly, fibrosis is not merely a downstream consequence of microvascular injury. Altered ECM may increase diffusion distance, modify mechanotransduction, impair endothelial survival and migration, and restrict capillary reopening and regeneration. We use the term matrix locking to describe this sustained constraint on vascular repair, while emphasizing that current evidence does not establish irreversible disease in humans. This framework also has therapeutic implications. PTC-directed treatment should not be reduced to increasing vessel number or uniformly promoting angiogenesis. Instead, intervention should be matched to the dominant and potentially reversible abnormality: preserving endothelial barrier function; restoring endothelial-pericyte stability and reducing pathological microvascular resistance; normalizing angiogenesis so that vascular growth is accompanied by maturation, barrier competence, network integration, and effective perfusion; and, in advanced rarefaction, relieving matrix-related constraints while supporting vascular regeneration. The context- and time-dependent effects of signaling through VEGF, Tie2, PDGF-B/PDGFRβ, eNOS/NO, and related pathways indicate that the same molecular signal may exert different effects depending on disease context and timing. Therapeutic efficacy should therefore be evaluated by restoration of effective microcirculation and tissue function rather than by isolated molecular changes or capillary counts alone. Despite increasing mechanistic evidence, the translational basis for this framework remains limited. Most causal and interventional data derive from animal or cell models, whereas human evidence is largely limited to pathological observations, patient-sample associations, and prognostic studies. Currently available circulating and urinary candidate biomarkers generally lack sufficient specificity for PTC injury or state assignment, and no standardized quantitative thresholds have been externally validated. The four-state model should therefore be regarded as a hypothesis-generating analytical framework rather than a clinicopathological classification system. Future studies should integrate spatially resolved tissue phenotyping, blood and urine biomarkers, and dynamic microcirculatory assessment in longitudinal cohorts. They should test reproducibility, assess prognostic value beyond conventional pathology, estimated glomerular filtration rate, and proteinuria, and determine whether changes in PTC status precede or mediate therapeutic benefit. Linking reproducible microvascular phenotypes to defined mechanisms, treatment response, and long-term renal outcomes will be essential to determine whether state-directed assessment and restoration of the PTC microenvironment can ultimately inform patient stratification and therapeutic decision-making.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective:Analysis of the composition of pathogen spectrum and prevalence characteristics in throat swabs of patients with acute respiratory infections (ARI) in Yucheng city, Henan province, from March to June 2023.Methods:After 1 153 throat swabs were collected from ARI patients in Yucheng, 18 respiratory pathogens were tested using a real-time fluorescence quantitative polymerase chain reaction (qPCR) method. The characterization of pathogens spectrum was analyzed.Results:A total of 1 153 throat swabs from ARI patients were collected from March to June 2023 in Yucheng, including 171 outpatients and 982 hospitalized patients. A total of 244 positive samples for common respiratory pathogens were detected (at least one pathogen per sample was detected). The total detection rate of respiratory pathogens was 21.16%, and the top three detection rates were, in descending order, human bocavirus (HBoV), enterovirus (EV), and human parainfluenza virus (HPIV). The main detection month for pathogens was May, with a detection rate of 42.3% (60/142). The main respiratory pathogens detected are HBoV, EV, and HPIV. The detection rate of the age group under 1 year old was the highest, at 25.1% (49/195), mainly consisting of HBoV, respiratory syncytial virus (RSV), and HPIV. The main clinical manifestations of respiratory pathogen-positive patients were fever and cough, and the clinical diagnosis was mainly lower respiratory tract infection, all of which were hospitalized patients.Conclusions:The respiratory pathogens in ARI patients were mainly HBoV, EV, and HPIV from March to June, 2023 in Yucheng. The peak of the epidemic was in May, mainly infecting children under 5 years of age.

Objective:To investigate the clinical characteristics, imaging features, risk factors, and prognosis of childhood-onset Takayasu arteritis (TAK) with pulmonary artery involvement.Methods:A retrospective cohort study was conducted in 107 pediatric patients who were initially diagnosed with childhood-onset TAK at Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical Universiy, from January 2010 to December 2024. Clinical data, including demographic information, imaging features, treatment regimens, and prognosis were collected. Patients were divided into with and without pulmonary artery involvement groups. Intergroup comparisons were performed. Multivariate logistic regression was used to identify risk factors for pulmonary artery involvement. Kaplan-Meier analysis with Log-Rank testing was used for survival analyze.Results:Among 107 children with TAK, 26 were male, 81 were female, with a diagnosis age of 88 (5, 137) months. Sixteen cases were in the pulmonary artery involvement group and 91 cases in the non-pulmonary artery involvement group. The pulmonary artery involvement group was predominantly female (14 cases), with a diagnosis age of 39 (4, 104) months. The pulmonary artery involvement group had higher incidence rates of fatigue,pulmonary hypertension, right heart failure,superior mesenteric artery involvement,as well as higher neutrophil counts, C-reactive protein (CRP) levels (all P<0.05). Hemoglobin was lower in the pulmonary artery involvement group ( P<0.05). Imaging findings revealed that all 16 children in the pulmonary artery involvement group showed signs of pulmonary arterial wall thickening. Other manifestations included dilation in 2 cases, stenosis in 2 cases, and occlusion in 1 case. Unilateral involvement (12 cases) was more common, and the right pulmonary artery (10 cases) was more frequently affected. Independent risk factors for pulmonary artery involvement in childhood-onset TAK patients included superior mesenteric artery involvement ( OR=5.58, 95% CI 1.41-22.10, P=0.014) and elevated CRP levels ( OR=1.02, 95% CI 1.00-1.03, P=0.027). During a follow-up of 3.9 (1.4,8.1) years, 2 patients with pulmonary artery involvement (all with pulmonary hypertension), among the survivors in the pulmonary artery involvement group, 2 cases still exhibited persistent pulmonary artery dilation, and one case had pulmonary artery occlusion; and 6 patients (6.6%) without pulmonary artery involvement died. Patients with pulmonary artery involvement had significantly lower survival rates compared to those without involvement ( P=0.024). Conclusions:Childhood-onset TAK with pulmonary artery involvement has an insidious clinical presentation, and can progress to pulmonary hypertension, pulmonary artery occlusion, and a significantly reduced survival rate. Patients with mesenteric artery involvement or elevated CRP have higher risks of pulmonary artery involvement, requiring close pulmonary vascular monitoring and early intervention to improve prognosis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

AIM To investigate the protective effects of verbascoside on D-galactose-induced liver injury in mice and its underlying mechanisms.METHODS C57BL/6J mice were randomly assigned to the normal group,the model group,the vitamin E group(100 mg/kg),and the low-dose and high-dose verbascoside groups(40,80 mg/kg),with 10 mice in each group.Simultaneous administration of medicine and subcutaneous injection of D-galactose(600 mg/kg)went on among the groups except the normal group for 8 weeks.Serum ALT,AST,ALP activities,along with TBil levels were measured using biochemical kits.Hepatic GSH,MDA concentrations,as well as SOD and GSH-Px activities were quantified.Liver pathological morphology was evaluated by HE staining,while hepatic fibrosis area was assessed using Sirius red staining.Western blot analysis determined hepatic expression of IL-6,IL-1β,TNF-ɑ,TLR4,NF-κB p65,IκBɑ and p-IKBɑ proteins.RESULTS Compared to the model group,the groups treated with vitamin E or verbascoside demonstrated significantly reduced body weight(P＜0.05,P＜0.01);increased hepatic index(P＜0.05,P＜0.01);decreased serum activities of ALT,AST and ALP alongsided reduced TBil levels(P＜0.05,P＜0.01);attenuated pathological damage of liver tissue and fibrosis severity;reduced hepatic MDA level(P＜0.05,P＜0.01);and elevated GSH level with enhanced SOD and GSH-Px activities(P＜0.05,P＜0.01).Furthermore,the high-dose verbascoside group showed significantly decreased hepatic expressions of IL-6,IL-1 β,TNF-ɑ,TLR4,NF-κB p65,and p-IKBɑ/IKBɑ proteins(P＜0.05,P＜0.01).CONCLUSION Verbascoside improves D-galactose-induced liver injury through its antioxidant activity,anti-inflammatory effects,and suppression of the TLR4/NF-κB signaling pathway.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.