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 The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

Objective:To investigate level and influencing factors of information overload of intensive care unit (ICU) patients′ decision-making agents in order to provide positive clinical interventions for improving their information overload.Methods:During March 2023 to February 2024, 302 ICU patients′ decision-making agents from the Second Affiliated Hospital of Naval Medical University of the People′s Liberation Army of China were cross-sectional surveyed by Basic Information Questionnaire, Information Overloading Scale, Decision Participation Expectancy Scale, Multidimensional Perceived Social Support Scale, State Trait Anxiety Inventory, Vickers Forest Physician Trust Scale, Decision Preparation Scale, Decision Fatigue Scale and Information Literacy Scale through convenience sampling methods.Results:In the valid 297 questionnaires, there were 172 males and 125 females in ICU patients′ decision-making agents aged 28-69(47.94 ± 8.71) years. The score of information overload was (19.65 ± 7.71), the score of perceived social support was (52.34 ± 7.87), the score of state anxiety was (60.88 ± 6.16), the score of trait anxiety was (60.09 ± 5.49), the score of physician trust was (35.34 ± 4.30), the score of preparation of decision was (27.90 ± 3.01), the score of decision fatigue was (20.61 ± 3.30), and the score of information literacy was (56.18 ± 11.46) in ICU patients′ decision-making agents. Linear regression analysis showed that age, educational level, having a common decision-maker, times of making medical decisions, type of participating in medical decision (cooperative type and proactive type), perceived social support, state anxiety, physician trust, preparation for decision making, decision fatigue and information literacy were all significant influencing factors of information overload of ICU patients′ decision-making agents ( t values were -6.76 to 7.57, all P<0.05). Conclusions:The level of information overload of ICU patients′ decision-making agents was above average. Therefore, while educating them about patients′ illness situation and inviting them to participate in decision-making, ICU medical staff should pay attention on their level of information overload, and then select simply easy communication methods and content to help them quickly understand information and make decisions according to their characteristics and information processing ability.

Objective: This study aims to investigate the anatomical relationship among the nerve roots, intervertebral space, pedicles, and intradural rootlets of the cervical spine for improving operative outcomes and exploring neuroventral decompression approach in posterior endoscopic cervical discectomy (PECD). Methods: Cervical computed tomography myelography imaging data from January 2021 to May 2023 were collected, and the RadiAnt DICOM Viewer Software was employed to conduct multiplane reconstruction. The following parameters were recorded: width of nerve root (WN), nerve root-superior pedicle distance (NSPD), nerve root-inferior pedicle distance (NIPD), and the relationship between the intervertebral space and the nerve root (shoulder, anterior, and axillary). Additionally, the descending angles between the spinal cord and the ventral (VRA) and dorsal (DRA) rootlets were measured. Results: The WN showed a gradual increase from C4 to C7, with measurements notably larger in men compared to women. The NSPD decreased gradually from the C2–3 to the C5–6 levels. However, the NIPD showed an opposite level-related change, notably larger than the NSPD at the C4–5, C5–6, and C7–T1 levels. Furthermore, significant differences in NIPD were observed between different age groups and genders. The incidence of the anterior type exhibited a gradual decrease from the C2–3 to the C5–6 levels. Conversely, the axillary type exhibited an opposite level-related change. Additionally, the VRA and DRA decreased as the level descended, with measurements significantly larger in females. Conclusion A prediction of the positional relationship between the intervertebral space and the nerve root is essential for the direct neuroventral decompression in PECD to avoid damaging the neural structures. The axillary route of the nerve root offers a safer and more effective pathway for performing direct neuroventral decompression compared to the shoulder approach.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

Objective:To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele(VC)with male infertility.Methods:A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis.The patients were divided into the microscopic group(180 cases)and laparoscopic group(127 cases)according to the surgery method.The pre-and postoperative clinical data of these two groups were analyzed,including the degree of dilatation and reflux time of internal spermatic vein,hemodynamic parameters of testicular capsular artery,proportion of progressive motility spermato-zoa(PR),concentration of spermatozoa,proportion of normal morphology sperm,the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively.Results:All the surgeries for the 307 patients in this study were successful.There was no significant difference in operation time,hospitalization time and management expenses between the microscop-ic group and the laparoscopic group(P＞0.05).Compared to the patients in laparoscopic group,the patients in the microscopic group received a better improvement in venous diameter,reflux time of spermatic veins and hemodynamic parameters of testicular capsular ar-tery(P＜0.05).Moreover,the semen analysis showed that the PR,spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group(P＜0.05).During the 2-year fol-low-up period,the conception rate of spouses in the microscopic group was 67.2％,while only 47.2％in the laparoscopic group,in which the difference was statistically significant(P＜0.05).Besides,the time-to-pregnancy(TTP)within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group(P＜0.05).Meanwhile,the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group(P＜0.05).It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group(P＜0.05).Severe complication such as testicular atrophy,bleeding and infection did not appear in both of two groups.However,the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group(P＜0.05).Conclusion:Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility.But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters,semen quality,pregnancy outcome and postopera-tive complications,which is worthy of further clinical applications.