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: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective To analyze the expression levels of natural cytotoxicity receptor(NCR)NKp46,NKp30,NKG2A and NKG2D in peripheral blood of non-small cell lung cancer(NSCLC)patients and its clinical diagnostic value.Methods A total of 50 NSCLC patients admitted to Affiliated Shijiazhuang Ping'an Hospital of Hebei University of Chinese Medicine from October 2021 to August 2022 were selected as the study group(NSCLC group).Meanwhile,20 healthy individuals who underwent physical examinations during the same period were selected as the control group.Peripheral blood samples were collected and the positive expression rate of NKp4,NKp30,NKG2A and NKG2D on NK cell surface was detected by flow cytometry.Clinical data from patients was collected and the correlation between the positive expression rate of NKp46,NKp30,NKG2A and NKG2D and pathological type,TNM staging and survival time were analyzed by One-way ANOVA/t test.Results Compared to control group,the positive expression rate of NKp46 on NK cells in peripheral blood of NSCLC patients were significantly elevated(42.09%±18.55%vs 25.92%±14.03%),the difference was statistically significant(t=3.511,P＜0.01).Comparison of the positive expression rates of NKG2A,NKG2D and NKp30 between the two groups and the differences were not statisticany significant(t=0.447,0.536,1.941,all P＞0.05).Subgroup analysis of NK cells revealed a significant increase in the proportion of CD56brightCD16+NK subgroups in NSCLC group compared to control group(3.76%±1.91%vs 2.42%±0.85%),the difference was statistically significant(t=3.017,P＜0.01).The positive expression rate of NKp46 in the CD56brightCD16+NK subgroup and CD56dimCD16+NK subgroup significantly increased(59.64%±21.12%vs 43.91%±16.04%,51.32%±19.84%vs 38.69%±15.12%),the differences were statistically significant(t=2.999,2.562,all P＜0.01).There was no significant difference in the positive expression rate of NKp46,NKG2A,NKG2D and NKp30 among squamous cell carcinoma and adenocarcinoma in lung(t=0.188～0.600,all P＞0.05).As TNM progresses,the positive expression rate of NKp46 on peripheral blood NK cells in NSCLC patients decreases,but the trend is of no statistical difference(F=2.381,P=0.10).Compared to patients with survival period≤12 months,the positive expression rate of NKp46 in patients with survival period>12 months was significantly higher(49.77%±17.52%vs 36.71%±15.41%),the difference was statistically significant(t=2.716,P＜0.01).Conclusion The positive expression rate of NKp46 in peripheral blood NK cells of NSCLC patients is increased,mainly in the CD56dimCD16+NK subgroup and CD56brightCD16+NK subgroup.The expression of NKp46 is related to the survival time of NSCLC patients,but not to the pathological type.Peripheral blood NCR NKp46 can serve as a potential biomarker for the diagnosis and prognostic evaluation of NSCLC.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

One patient with kidney stones was prescribed Paishi granules and diclofenac sodium sustained-release tablets for pain relief in the outpatient setting.That evening,the patient took 1 sachet of Paishi granules and 1 diclofenac sodium sustained-release tablet together.The patient subsequently developed a generalized rash with itching.Liver function indexes of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-BiL),direct bilirubin(D-BiL),and alkaline phosphatase(ALP)were all 2 to 6 times higher than the upper limit of normal.After symptomatico treatment,the patients systemic rash had subsided,and the liver function indicators have returned to normal.

Objective To investigate the dosimetric effect of a biological optimization approach combining physical optimization with generalized equivalent uniform dose(gEUD)on hippocampus avoidance whole-brain radiotherapy(HA-WBRT).Methods A retrospective review was conducted of 20 patients with multiple brain metastases who underwent whole-brain radiotherapy at a certain hospital between May 2021 and December 2022.Two radiotherapy plans including plan_DV and plan_gEUD were designed for each patient by using Eclipse V15.6 planning system.Plan_DB used conven-tional dose-volume(DV)physical optimization,and plan_gEUD went through re-optimization with an Upper gEUD function applied to hippocampal region and hippocampal protection zone.Evaluation was carried out in accordance with RTOG 0933 guidance for the absolute values D2%,D98%and D50%received by 2%,98%,and 50%of the target volume in the planning target volume,conformity index(CI),homogeneity index(HI),gradient index(GI)and the dosimetric indexes of hippocampal region,hippocampal protection zone and other organs at risk(OARs).SPSS 26.0 software was used for statistical analysis.Results The two kinds of plans both had the target volume coverage meet the requirements of RTOG 0933 guidance.Plan_gEUD had the D98%,D2%and V105 of the planning target volume lower than those of plan_DV,with the differences being statistically significant(all P<0.05).The two kinds of plans had no significant differences in monitor unit,D50%and Dmax of PTV,HI,CI and GI(all P>0.05).Plan_gEUD had the Dmax and Dmean of hippocampal region and them of hippocampal pro-tection zone lower than those of plan_DV,and the optic nerve Dmax of plan_gEUD was higher than that of plan_DV,with the differences being statistically significant(all P<0.05).There were no statistically significant differences between the two kinds of plans in the Dmax of inner ear,optic chiasm,lens,and eyeball(all P>0.05).Conclusion Physical optimization in the HA-WBRT plan combined with gEUD optimization results in a greater dose reduction to the hippocampus while maintaining target coverage.

Objective To evaluate the impact of slow-freezing process on human ovarian tissue with the standard cryopreservation-thawing protocol of Fertility Protection Center of Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Methods Ovarian tissues of 12 patients were divided into fresh ovarian tissue group(fresh group)and freezing-thawing ovarian tissue group(F-T group).The freezing-thawing protocol was the standard protocol in our center.The number and activity of follicle were examined with Hematoxylin-eosin(HE)staining and calcein-AM(calcein acetoxymethylester)staining,and the proliferation and apoptosis was evaluated with the immunohistochemical staining of Ki-67 and caspase-3.The expressions of apoptosis-related proteins such as caspase-3,bax and FasL between the two groups were compared with Western blotting.Results There were no statistically significant differences in follicle counting and follicle activity in ovarian tissues pre-and post-freezing-thawing(P>0.05),and the positive rate of Ki-67 in ovarian tissues after freezing-thawing was significantly lower than that in fresh ovarian tissues(P<0.05),and there was no statistically significant difference in the positive rate of caspase-3 between the two groups(P>0.05).The expression of caspase-3 protein in ovarian tissues after freezing-thawing was significantly higher than that in fresh ovarian tissues(P<0.05),while the expressions of other apoptosis-related proteins such as bax and FasL were not significantly different(P>0.05).Conclusion The standard cryopreservation-thawing regimen in our center can effectively maintain the follicle number,morphology,and activity in ovarian tissues.After freezing and thawing,the cell proliferation level is decreased.The expression of apoptosis-related proteins such as bax and FasL are not increased,and the expression of caspase-3 is relatively increased.These results suggest our freezing-thawing regimen is good for human ovarian tissue.

Female infertility is recognized as a global public health issue by the World Health Organization.Female fertility remodeling includes ovarian function reconstruction and uterus/endometrium reconstruction,etc.It is emerging as a hot technology since it is ready to prepare autologous platelet-rich concentrate and it is safer and more acceptable in autologous application.It plays an important role in regenerative medicine,and it is currently widely applied in maxillofacial and plastic surgery,dermatology and other clinical practices.This article mainly reviews the progresses of the application of autologous platelet-rich concentrate in female fertility remodeling.

Objective To explore the effect of a multicomponent exercise and cognitive stimulation program in elderly patients with mental disorders and sarcopenia,so as to provide references for reducing the risk of falls,preventing and improving sarcopenia,and enhancing cognitive function in patients.Methods The multi-component exercise and cognitive stimulation program was formulated through literature review and expert meeting.In this quasi-experimental study,76 elderly patients with mental disorders and sarcopenia who were hospitalized in a tertiary mental health center in Shanghai from January 2023 to February 2024 were selected as research subjects.They were randomly divided into an experimental group and a control group according to their hospitalization building number(38 cases in each group).The experimental group was treated with multicomponent exercise combined with cognitive stimulation program based on routine nursing,and the control group was treated with routine nursing.The risk of falls,skeletal muscle mass,muscle strength,physical function,cognitive function,and incidence of adverse events were compared between 2 groups after 12 weeks of intervention.Results A total of 75 patients with 37 in the control group and 38 in the experimental group completed the study.The TUG time,6M walking speed and the score of Short Physical Performance Bettery of the experimental group were all lower than those of the control group(P＜0.05),and the scores of skeletal muscle mass,muscle strength,calf circumference,physical function and cognitive function of the experimental group were all higher than those of the control group(P＜0.05).Neither group experienced any adverse events.Conclusion The application of this multicomponent exercise combined cognitive stimulation program developed for elderly patients with mental disorders and sarcopenia can effectively reduce the risk of falls,enhance the skeletal muscle mass and muscle strength and improve the cognitive function in elderly patients with mental disorders and sarcopenia.

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,oxypaeoniflorin,catechin,epicatechin,albiflorin,paeoniflorin,rutin,calycosin-7-glucoside,syringaldehyde,ferulic acid,coumarin,ononin,calycosin,cinnamic alcohol,cinnamic acid,benzoylpaeoniflorin,cinnamaldehyde,astragaloside,astragaloside Ⅲ,6-gingerol in Huangqi Guizhi Wuwu Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Thermo Scientific Hypersil GOLD column(150 mmx4.6 mm,3 μm),with the mobile phase comprising of 0.015％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion modes with multiple reaction monitoring.RESULTS Twenty-one constituents showed good linear relationships within their own ranges(r＞0.990 5),whose average recoveries were 93.99％-108.52％with the RSDs of 1.04％-5.97％.CONCLUSION This simple,feasible,stable and reliable method can be used for the quality control of Huangqi Guizhi Wuwu Decoction.