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 evaluate the diagnostic efficacy of different pathogen detection methods in active tuberculosis (ATB) of kidney transplant recipients (KTRs) and analyze their diagnostic value in different types of clinical specimens. Methods A retrospective observational study was conducted, including adult KTRs with suspected ATB from the Eighth Medical Center of Chinese People's Liberation Army General Hospital from January 2020 to January 2025. Baseline data of the recipients were collected and analyzed, and the diagnostic criteria were based on a composite reference standard (including clinical diagnosis and bacteriological confirmation). The single-detection efficacy of acid-fast staining smear, mycobacterium tuberculosis culture, Xpert test for the detection of mycobacterium tuberculosis nucleic acid and resistance to rifampicin (Xpert MTB/RIF), as well as tuberculosis or non-tuberculosis mycobacterial DNA detection was compared. The differences in sensitivity among different methods were analyzed. Results A total of 95 KTRs with suspected ATB and 136 specimens were included. And 52 cases were diagnosed as ATB, among which 48 cases were confirmed by bacteriological means (92%). The sensitivity of Xpert MTB/RIF and DNA detection (0.55 and 0.52, respectively) was significantly higher than that of acid-fast staining smear (0.30) and mycobacterium tuberculosis culture (0.35) (P < 0.01). There was a statistically significant difference in the bacteriological diagnosis rate among different specimen types (P = 0.035). The detection sensitivity of each method was the highest in pus, puncture tissue and bronchoalveolar lavage fluid, followed by sputum and pleural and abdominal effusions, and the lowest in cerebrospinal fluid. Conclusions The sensitivity of nucleic acid amplification technology for immunosuppressed KTRs is slightly reduced, but it should still be recommended as the preferred initial screening tool. The comprehensive strategy of "multi-site sampling (prior to obtaining high bacterial load specimens) combined with multiple method detection" may improve the diagnostic efficacy.

OBJECTIVE To investigate the effect and mechanism of Tangzhi formula（TZF） on improving glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats.METHODS Thirty SPF-grade SD rats were used to establish a T2DM rat model through high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats were divided into the model group， metformin group （positive control， 0.18 g/kg）， and TZF low-， medium-， and high-dose groups （5， 10， and 20 g/kg）， with 6 rats in each group. An additional 6 rats were selected as the blank group. The rats in each group were orally administered the corresponding volume of drug solution or saline， and continuous dosing was performed for 6 weeks， once daily. Fasting blood glucose （FBG）， area under the curve of oral glucose tolerance test （OGTT-AUC）， area under the curve of intraperitoneal insulin tolerance test （IPITT-AUC）， serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe hepatic pathological morphology and lipid deposition. Differentially expressed proteins in liver tissues were screened by proteomics analysis， and key proteins in signaling pathways were verified by Western blot and immunofluorescence staining.RESULTS Compared with the blank group， the levels of FBG， OGTT-AUC， IPITT-AUC， LDL-C， TG， and TC in the model group were significantly increased （ P ＜0.05）， while HDL-C level was significantly decreased （ P ＜0.05）； the liver tissues showed disordered hepatic cords， punctate necrosis of hepatocytes， and significant lipid deposition， the NAFLD activity score and positive area of lipid droplets were significantly increased（ P ＜0.05）. Compared with the model group， the above indicators in TZF low-， medium-， and high-dose groups and metformin group were significantly reversed （ P ＜0.05）； hepatic pathological injury and lipid deposition were alleviated. Proteomics results showed that a total of 442 differentially expressed proteins were screened between the model group and the blank group， and 358 differentially expressed proteins were screened between the TZF high-dose group and the model group. Among these differentially expressed proteins， multiple proteins closely related to glucose and lipid metabolism showed a reversal trend after TZF intervention. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the peroxisome proliferator-activated receptor （PPAR） signaling pathway was significantly enriched. The validation experiment results showed that TZF could significantly up-regulate the expression of PPARα， PPARγ， and apolipoprotein A1 （ApoA1） in rat liver tissues （ P ＜0.05）， and down-regulate the expression of stearoyl-CoA desaturase 1 （SCD1） and perilipin 2 （PLIN2） （ P ＜0.05）.CONCLUSIONS TZF can improve glucose and lipid metabolism disorders in T2DM rats； its mechanism may be related to the activation of the PPAR signaling pathway and the regulation of downstream lipid metabolism-related proteins SCD1， PLIN2， and ApoA1.

Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

Objective To observe the feasibility and accuracy of simplified prenatal ultrasonic evaluation on fetal bilateral lateral fissures.Methods A total of 513 pregnant women with gestational ages ranging from 20-34 weeks were prospectively enrolled.Transabdominal ultrasound screening of fetal bilateral lateral ventricular fissures on the transforaminal plane were performed,the ultrasonic display rate and characteristics like morphology of bilateral lateral fissures were recorded,and a simple grading system(3 levels)was applied for evaluating the fissures.Fetuses with abnormalities were further examined with MR,amniotic fluid/cord blood tests or whole-exome sequencing of umbilical cord tissue after birth.The pregnancy outcomes were documented.Results Normal fetal bilateral lateral fissures were observed using simplified prenatal ultrasonic evaluation in 500 fetuses whom were then successfully delivered,and normal cortical development was found in these 500 newborns,while abnormalities were detected in 13 fetuses.The display rate of transabdominal ultrasound on transforaminal plane for fetal bilateral lateral ventricular fissures was 92.20％(473/513).From 20 to 34 weeks,the morphology of bilateral lateral fissures could be simply graded into 3 levels:Level 1 presented as a shallow arc shape from 20-22 weeks,Level 2 presented as a blunt or right-angled broad platform from 22-26 weeks,and Level 3 presented as an acute-angled broad platform from 25-34 weeks.In 500 fetuses with normal development,the morphology of the near-field lateral fissures consistently developed in parallel with the far-field lateral fissures as gestational age increased.Among 13 fetuses with abnormal findings,abnormalities of bilateral lateral fissures were found in 8 fetuses,while unilateral abnormality was noticed in 5 fetuses.MR examination of all 13 fetuses and amniotic fluid whole-genome sequencing of 9 fetuses indicated abnormal cortical development.Conclusion Simplified prenatal ultrasound based on transforaminal column cross-section could conveniently and accurately classify morphology of fetal bilateral lateral sulcus.

Objective To understand the nursing practice of prone position ventilation for patients with moderate to severe acute respiratory distress syndrome(ARDS)in intensive care unit(ICU)in Shandong province,so as to provide basis for standardizing the nursing practice process of prone position ventilation and carrying out training for hospitals.Methods A self-made questionnaire was used,and convenience sampling was adopted.From September 15th to November 5th,2023,ICU nurses were selected from various hospital levels in Shandong province to investigate the obstructive factors of prone ventilation implementation,the weak links in nursing practice and status,and the occurrence of complications.Results A total of 1 188 questionnaires were collected,of which 991 were valid.92.8%(920/991)of nurses had performed prone position ventilation.The biggest obstacle to the implementation of prone position ventilation was the complexity of patient treatments and multiple devices involved[74.6%(686/920)].Regarding the status of training,90.5%(897/991)of nurses had received training on prone position ventilation and 77.0%(763/991)of nurses felt that training was needed.As for pre-operation assessment,more than 80.0%of nurses evaluated patients'vital signs,airway and secretions and so on,among which the evaluation awareness of analgesia was the worst[81.6%(751/920)].As for the main points of implementation,only 14.0%(129/920)of nurses chose the opposite side of the most important pipeline as the turning direction;48.6%(447/920)of nurses chose the anti-Trendelenburg position;36.3%(334/920)of nurses chose to ventilate≥12 hours.Facial edema[81.7%(752/920)],skin pressure injury[78.9%(726/920)]and eye complication[75.8%(697/920)]were the top 3 most frequent complications.Conclusions ICU nurses'prone position ventilation practices were generally line with the nursing team standard for prone position of adult mechanically ventilated patients and the best evidence recommendation,and needs to be further standardized in aspects of turning direction,position management,ventilation duration,and enteral nutrition management.It is recommended that nursing managers at all levels of hospitals further improve the quality of nursing practice of prone position ventilation according to relevant evidence-based evidence and the actual situation of hospitals.

Objective To determine the clinical effect of warmed iodophor for preoperative disinfection in elderly patients undergoing laparoscopic hysterectomy.Methods A total of 84 elderly patients who underwent laparoscopic hysterectomy were selected and randomly divided into the room temperature group(disinfected with iodophor at a temperature of 24℃)and the warmed group(disinfected with iodophor at a temperature of 39℃),with 42 cases in each group.The disinfection qualification status,incision infection status,nasopharyngeal temperature,awakening time,adverse reactions,intraoperative blood loss,incision drainage volume,and hidden blood loss of patients in the two groups were compared.Results There was no statistically significant difference in the disinfection qualification rate or incision infection rate between the two groups(P>0.05).At 10 minutes,30 minutes,60 minutes after disinfection and the end of the operation,the nasopharyngeal temperatures of patients in the warmed group were significantly higher than those in the room temperature group(P<0.05).The awakening time of patients in the warmed group was significantly shorter than that in the room temperature group(P<0.05),and the incidences of intraoperative hypothermia and shivering reaction after awakening were significantly lower than those in the room temperature group(P<0.05).There was no statistically significant difference in the intraoperative blood loss or incision drainage volume of patients between the two groups(P>0.05),while the hidden blood loss of patients in the room temperature group was significantly higher than that in the warmed group(P<0.05).Conclusion The iodophor at a temperature of 39℃for preoperative disinfection in elderly patients undergoing laparoscopic hysterectomy can not only ensure the disinfection effect and surgical safety,but also effectively maintain intraoperative body temperature stability,promote postoperative awakening,and reduce hidden blood loss.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

OBJECTIVE: To develop a digital intelligent multimodal shift handover system for the intensive care unit (ICU) and evaluate its application effect in ICU shift handovers. METHODS: A research and development team was established, consisting of 1 department director, 1 head nurse, 3 information technology engineers, 3 nurses, and 2 doctors. Team members were assigned responsibilities including overall coordination and planning, platform design and maintenance, pre-application training, collection and organization of clinical feedback, and research investigation respectively. A digital intelligent multimodal shift handover system was developed for ICU based on the Shannon-Weaver linear transmission model. This innovative system integrated automated data collection, intelligent dynamic monitoring, multidimensional condition analysis and visual reporting functions. A cloud platform was used to gather data from multi-parameter vital signs monitors, infusion pumps, ventilators and other devices. Artificial intelligence algorithms were employed to standardize and analyze the data, providing personalized recommendations for healthcare professionals. A self-controlled before-after method was adopted. Before the application of the ICU digital intelligent multimodal shift handover system (from December 2023 to March 2024), the traditional verbal bedside handover was used; from June 2024 to March 2025, the ICU digital intelligent multimodal shift handover system was applied for shift handovers. Questionnaires before the application of the shift handover system were collected in April 2024, and those after the application were collected in April 2025. The shift handover time, handover quality (scored by the nursing handover evaluation scale), satisfaction with doctor-nurse communication (scored by the ICU doctor-nurse scale) before and after the application of the handover system were compared, and nurses' satisfaction with the shift handover system (scored by the clinical nursing information system effectiveness evaluation scale) was investigated. RESULTS: After the application of the ICU digital intelligent multimodal shift handover system, the shift handover time was significantly shorter than that before the application [minutes: 20 (15, 25) vs. 30 (22, 40)], the handover quality was significantly higher than that before the application [score: 84.0 (78.0, 88.5) vs. 71.0 (55.0, 79.0)], and the satisfaction with doctor-nurse communication was also significantly higher than that before the application (score: 84.58±6.79 vs. 74.50±11.30). All differences were statistically significant (all P < 0.05). In addition, the nurses' system effectiveness evaluation scale score was 102.30±10.56, which indicated that nurses had a very high level of satisfaction with the ICU digital intelligent multimodal shift handover system. CONCLUSIONS The application of the ICU digital intelligent multimodal shift handover system can shorten the shift handover time, improve the handover quality, and enhance the satisfaction with doctor-nurse communication. Nurses have a high level of satisfaction with this system.
Intensive Care Units ; Humans ; Patient Handoff ; Artificial Intelligence ; Algorithms