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.

Objective To explore the distribution and epidemiological characteristics of single virus infection and mixed virus infection in patients with acute respiratory tract infection. Methods A retrospective study was conducted on 320 patients with acute respiratory tract infections who visited sentinel hospitals from January 2022 to January 2025. All patients underwent common virus detection and atypical pathogen human rhinovirus (HRV) detection. Results In this study, there were 204 patients (71.83%) with single virus infection, including 87 cases (42.65%) of atypical pathogen human rhinovirus (HRV) infection, 28 cases (13.73%) of influenza A virus infection, 35 cases (17.16%) of influenza B virus infection, 21 cases (10.29%) of respiratory syncytial virus (RSV) infection, 17 cases (8.33%) of adenovirus (ADV) infection, and 16 cases (7.84%) of parainfluenza virus (PIV) infection. There were 80 patients (28.17%) with mixed virus infection, including 57 cases (71.25%) of influenza virus+RSV mixed infection and 23 cases (28.75%) of ADV+PIV mixed infection. There were significant differences in the detection rates of HRV, RSV, influenza virus+RSV, and ADV+PIV among different age groups (P<0.05). The detection rates of HRV, RSV single and mixed virus were high in age of 0-5 years old, while the detection rate of ADV was high in age of ≥60 years old. Statistical differences were found in the detection rates of HRV, influenza A virus, influenza B virus, ADV, influenza virus+RSV, and ADV+PIV among different seasons (P<0.05). The detection rates of HRV, influenza A virus, influenza B virus, and RSV were high in spring and winter, the detection rates of ADV and ADV+PIV were high in summer, the detection rate of PIV was high in spring and autumn, and the detection rate of influenza virus+RSV was high in winter. There were no statistical differences in the detection rates of viral pathogens among patients with different genders (P>0.05). Conclusion Acute respiratory tract infection is mainly caused by single virus infection (HRV is the most common). Mixed infection is more common in influenza virus with RSV. Children aged 0-5 years old and elderly people over 60 years old are susceptible populations. Children have a higher risk of mixed infection, and the epidemic peak is concentrated in winter and spring.

Objective:To analyze the effect of continuous positive airway pressure (CPAP) on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome (OSAS), especially on the incidence of hypertensive disorder in pregnancy (HDP) in women with moderate to severe OSAS.Methods:A total of 180 pregnant women with OSAS who were diagnosed through sleep monitoring during pregnancy due to high-risk factors of OSAS and registered in Peking University People′s Hospital from January 2021 to May 2024 were selected as the study subjects. Clinical data were collected from medical records for retrospective analysis. According to whether they received standardized treatment with CPAP, they were divided into the CPAP treatment group (42 cases) and the control group (138 cases). The CPAP treatment group consisted of 9 pregnant women with moderate to severe OSAS, while the control group consisted of 34 pregnant women with moderate to severe OSAS. The maternal and neonatal outcomes, the incidence of HDP, placental weight after delivery and placental weight/neonatal birth weight ratio were compared between the two groups.Results:(1) The average gestational age of pregnant women in the CPAP treatment group was higher than that in the control group [(38.7±1.0) vs (38.0±1.4) weeks], the proportion of infants small for gestational age (SGA) in the CPAP treatment group was lower [0 (0/42) vs 12.3% (17/138)], and the birth weight of infants in the CPAP treatment group was bigger [(3 396±475) vs (3 082±710) g); the differences between the two groups were statistically significant (all P<0.05). There were no significant differences between the CPAP treatment group and the control group in terms of delivery mode, rates of postpartum hemorrhage and preterm birth, umbilical artery blood gas analysis pH<7.1, lactate≥6.0 mmol/L, base excess<-12.0 mmol/L and the incidence of gestational diabetes mellitus and HDP (all P>0.05). (2) The placental weight of the CPAP treatment group was significantly lower than that of the control group [(554.0±70.6) vs (615.7±119.1) g], the placental weight/newborn birth weight ratio of the CPAP treatment group was significantly lower than that of the control group (median: 0.17 vs 0.19), and the differences were statistically significant (all P<0.05). (3) The incidence of HDP in pregnant women with moderate to severe OSAS in the CPAP treatment group was lower than that in the control group [1/9 vs 61.8% (21/34)], and the difference was statistically significant ( P<0.05). Conclusions:CPAP treatment could prolong the gestational age in pregnant women with OSAS, reduce the incidence of SGA, increase the birth weight of infants, and reduce the incidence of HDP in pregnant women with moderate to severe OSAS, and is worth promoting in clinical practice. The improvement of neonatal outcomes by CPAP treatment is closely related to the placenta, which is worthy of further exploration.

Objective:To investigate the incidence, risk factors, and outcomes of falls among the elderly community population in Beijing.Methods:A cross-sectional survey was conducted using stratified multistage random sampling to select urban and rural residents aged 65 years and older in Beijing. Mortality data was collected after the baseline survey for 5 years. The incidence of falls was weighted based on the composition ratios of age and gender from the 2010 Nation-wide Population Census of Beijing. A logistic regression model was used to analyze the impacts of demographic sociology of common chronic diseases on fall occurrence. The Cox proportional hazards regression model was used to analyze the fall and 5-year survival association.Results:A total of 2 968 participants completed the questionnaire, at cross-sectional survey, with an average age of (73.2±6.0) years, and 1 581 (53.8%) participants were female. Three hundred and sixty-one individuals experienced a fall within the past year. Among those who fell, 64 (17.7%) fell twice, and 95 (26.6%) fell three or more times. Of them, 14.4% (52) had post-fall fractures, with the wrist, knee, and hip being the most common fracture sites, accounting for 25.0%, 17.3%, and 15.4%, respectively. The weighted fall incidence was 12.4% (95% CI: 11.2%-13.5%). Aging, being female, and living in rural areas were more likely to fall. Logistic regression analysis showed that after adjusting for age, gender, and urban-rural status, the risk of falls for those living alone ( OR=1.48, 95% CI: 1.08-2.04) or living with children/grandchildren ( OR=1.51, 95% CI: 1.15-1.97) were significantly higher than those living with their spouse. In addition, the risk of falls was elevated significantly among the elderly with hypertension, diabetes, stroke, dementia, depression status, urinary incontinence, arthritis, insomnia, vision, and hearing loss, dependence on activities of daily living (ADL), general and poor self-rated health (SRH). The Cox proportional hazard regression model revealed that the 5-year risk of death increased by 65% ( HR=1.65, 95% CI: 1.29-2.11) for those who experienced a fall, which increased with fall frequency. This elevated risk persisted after adjusting for chronic conditions, ADL, and SRH. Conclusions:Ageing, female, living in rural regions, having common chronic diseases, dependence on ADL, general and poor SRH, living alone or living with children/grandchildren were associated with the elevated fall risk. The occurrence of fall was seasonal. The most common short-term adverse consequence after a fall was fractures, while the long-term effect was an increased risk of death.

OBJECTIVE T o explore the distribution of pathogens and risk factors for hospital-associated infections in the laryngeal cancer patients undergoing tracheotomy so as to provide theoretical bases for reasonable clinical use of antibiotics.METHODS Totally 118 laryngeal cancer and tracheotomy patients who were complicated with infec-tions and treated in otolaryngology head and neck surgery department of The First Medical Center of Chinese PLA General Hospital from Oct.2021 to Oct.2024 were retrospectively assigned as the infection group,meanwhile,the 118 patients who were not complicated with infections were chosen as the no infection group.The distribution and drug susceptibility rates of the pathogens isolated from clinical specimens of the patients with infections were observed,and the risk factors for the hospital-associated infections were explored.RESULTS Totally 168 strains of pathogens were isolated from the 118 patients with infections,107 of which were gram-negative bacteria,51 were gram-positive bacteria,and 10 were fungi.The result of multivariate logistic regression analysis showed that age(OR=2.435,95％CI:1.052 to 5.634),duration of tracheotomy(OR=3.525,95％CI:1.871 to 14.259),length of hospital stay(OR=2.829,95％CI:1.099 to 7.276)and complication with diabetes mellitus(OR=4.807,95％CI:1.704 to 13.557)were the risk factors for the hospital-associated infections in the laryngeal cancer pa-tients undergoing tracheotomy(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the laryngeal cancer and tracheotomy patients with hospital-associated infections.The age,duration of tracheotomy,length of hospital stay and complication with diabetes mellitus are the risk factors for the hospital-associated infections in the laryngeal cancer patients undergoing tracheotomy.It is necessary to formulate the prevention and control measures based on the above factors so as to reduce the incidence of infec-tions.

Objective To analyze the mutation status of Kirsten rat sarcoma viral oncogene homolog(KRAS),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),v-raf murine sarcoma viral oncogene homolog B1(BRAF)genes,and the expression of mismatch repair(MMR)and human epidermal growth factor receptor 2(HER-2)proteins in tumor tissues of patients with colorectal cancer(CRC)harboring neuroblastoma rat sarcoma viral oncogene homolog(NRAS)gene mutations,and explore their relationships with the clinicopathological characteristics of CRC patients.Methods The clinicopathological data of 546 patients with NRAS mutation CRC were retrospectively analyzed.The mutation status of NRAS,KRAS,PIK3CA,and BRAF genes was detected by AmoyDx amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)kit(fluorescent PCR method),the expression levels of MMR and HER-2 proteins were detected by immunohistochemical staining EnVision method,and the relationship between them and the clinicopathological characteristics of patients were analyzed.Results The mutation rate of single-point mutations in the NRAS gene was 98.35%(537/546),double-point mutations in the NRAS gene were 1.65%(9/546),and double mutations in the NRAS and KRAS genes were 1.47%(8/546).No patients were found to harbor mutations in the PIK3CA or BRAF genes.The types of NRAS mutations included Q61R(or Q61K,Q61L,Q61H)mutations(266/546,48.72%),G12D(or G12S)mutations(154/546,28.21%),G13R(or G12C,G12V,G12A,G13V)mutations(134/546,24.54%),and A146T mutation(1/546,0.18%).G13R(or G12C,G12V,G12A,G13V)mutations in the NRAS gene were more likely to occur in the rectum cancer patients(P=0.035);although the tumors had a larger diameter(P=0.029),the patients had a longer progression-free survival after surgery(P=0.028).Among patients with NRAS gene mutations,HER-2 positive expression was associated with perineural invasion(P=0.003),and the patients with deficient MMR were younger on average(P=0.041)and were associated with double-point mutations in the NRAS gene(P=0.018).Conclusion CRC harboring NRAS mutations may have unique clinicopathological characteristics and molecular phenotypes,providing possibilities for individualized treatment and prognosis evaluation of CRC.

The rapid and non-destructive detection of constituent content of fresh tea leaves shows an important reference value for quality identification of tea.Visible near infrared(Vis-NIR)spectroscopy has been used for qualitative and quantitative analysis of chemical components in plant samples with the advantages such as simple,rapid and non-destructive detection.In this study,residual attention convolutional neural network(RACNN)was used to predict the internal constituent content of fresh tea leaves.Firstly,the reflectance spectral data of the samples in the Vis-NIR band range and the constituent contents of gallic acid(GA),gallocatechin(GC),epigallocatechin(EGC),and epigallocatechin gallate(ECG)in fresh tea leaves were collected.Based on the preprocessing of the spectral data,the contents of the four components were predicted using a partial least squares regression(PLSR)model,and the optimal preprocessing was determined.Subsequently,the characteristic bands were extracted using the random forest(RF)algorithm.Finally,the performances of PLSR,convolutional neural network(CNN)and RACNN models were compared.The results showed that for GA,the RACNN model worked best with a validation set coefficient of determination(R2)of 0.946 and a root mean square error of the prediction set(RMSEP)of 1.173;for GC,the RACNN model works best with a validation set R2 of 0.928 and RMSEP of 6.081;for EGC,the RACNN model works best with a validation set R2 of 0.891 and a RMSEP of 15.197;for ECG,the RACNN model worked best with a validation set R2 of 0.878 and a RMSEP of 7.837.The RACNN model established by Vis-NIR spectroscopy combined with chemometrics could realize the accurate detection of the contents of components in fresh tea.

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

BACKGROUND: Primary pulmonary mucoepidermoid carcinoma (PMEC) is an exceedingly rare malignancy originating from bronchial submucosal glands, accounting for <0.2% of lung cancers. Histologically characterized by a triphasic composition of mucinous, epidermoid, and intermediate cells, PMEC is classified into low-grade (favorable prognosis) and high-grade (aggressive behavior) subtypes. This study aimed to investigate the clinicopathological characteristics and prognostic indicators of PMEC. METHODS: Clinicopathological, radiological, molecular, and survival data from 26 PMEC patients were retrospectively analyzed, including immunohistochemical profiles and MAML2 rearrangement status, supplemented by literature review. RESULTS: The cohort comprised 14 males and 12 females (mean age: 55.6 years). Eight patients (30.8%) were smokers, and 19 (73.1%) presented with symptoms. Central tumors predominated (n=19, 73.1%) versus peripheral lesions (n=7, 26.9%). Computed tomography (CT) imaging consistently revealed hypo-to-isodense masses/nodules. Pathologically, 19 cases were low-grade and 7 high-grade. Immunohistochemically, the tumor cells were positive for CK7, P40, P63 and CK5/6, and the Ki-67 index ranged from 2% to 70%. MAML2 rearrangement was detected in 52.4% (11/21) of tested cases. Clinical staging distribution: stage I (n=14), stage II (n=8), stage III (n=3), stage IV (n=1). Treatment modalities: radical surgery alone (n=13), surgery with adjuvant chemotherapy (n=11), chemoradiotherapy (n=1), and conservative management (n=1). With a median follow-up of 57 months, 6 patients (23.1%) died. Prognostic analysis demonstrated: (1) Significantly inferior survival in high-grade versus low-grade groups (P<0.05); (2) Lymph node metastasis, advanced stage, Ki-67>20%, and high-grade histology significantly correlated with reduced overall survival (P<0.05); (3) Lymph node metastasis constituted an independent poor prognostic factor (HR=12.73, 95%CI: 1.22-132.96). CONCLUSIONS PMEC exhibits distinct clinicopathological features, with MAML2 rearrangement present in approximately half of cases. Lymph node metastasis, advanced stage, high Ki-67 proliferation index, and high-grade histology are key determinants of poor prognosis, with lymph node metastasis serving as an independent risk factor.
Humans ; Male ; Female ; Middle Aged ; Carcinoma, Mucoepidermoid/mortality* ; Lung Neoplasms/mortality* ; Trans-Activators/genetics* ; Prognosis ; Adult ; Gene Rearrangement ; Aged ; Retrospective Studies ; Transcription Factors/genetics* ; DNA-Binding Proteins/genetics*