Tumor resistance to anti-mesothelin CAR-T cells caused by binding to shed mesothelin is overcome by targeting a juxtamembrane epitope.

Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.

Combined radiomics nomogram of different machine learning models for preoperative distinguishing intraspinal schwannomas and meningiomas: a multicenter and comparative study.

AIMS: The objective of our study was to establish and verify a novel combined model based on multiparameter magnetic resonance imaging (MRI) radiomics and clinical features to distinguish intraspinal schwannomas from meningiomas. MATERIALS AND METHODS: This research analyzed the preoperative magnetic resonance (MR) images and clinical characteristics of 209 patients with intraspinal tumors who received tumor resection at three institutions. 159 individuals from institutions 1 and 2 were randomly assigned into a training group (n=111) and a test group (n=48) in a 7-3 ratio. A nomogram was constructed using the training cohort and was internally and externally verified in the test cohort and an independent validation cohort (n=50). Model performance was assessed utilizing the area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration curves. RESULTS: The nomogram exhibited superior predictive efficacy in distinguishing between spinal schwannomas and meningiomas when compared to both the radiomics model and the clinical model. The nomogram yielded AUCs of 0.994, 0.962, and 0.949 in the training, test, and external validation cohorts, respectively, indicating its exceptional differentiating ability. The DCAs demonstrated that the nomogram yielded the best net benefit. The calibration curves indicated that the nomogram got good agreement between the predicted and the actual observation. CONCLUSION: This research suggests that the nomogram incorporating clinical and radiomic features may be an effective auxiliary tool for distinguishing between intraspinal schwannomas and meningiomas, and has important clinical significance for clinical decision-making and prognosis prediction.

[Clinical pathway in Chinese county for lung cancer diagnosis and treatment (2023 edition)].

Lung cancer (LC) is the leading cause of death among patients with cancer both in worldwide and China. China accounts for 11.4% of the total number of cancer cases and 18.0% of the total number of cancer deaths in the world. Standardizing the diagnosis and treatment of LC is a key measure to improve the survival rate of LC patients and reduce the mortality rate. However, county hospitals generally face the problem of inaccessibility to advanced diagnostic and treatment technologies. Therefore, when developing quality control standards and clinical diagnosis and treatment specifications, it is necessary to combine the actual situation of county hospitals and formulate specific recommendations. The recommendations of treatment measures also need to consider the approval status of indications and whether it is included in the National Reimbursement Drug List (NRDL), to ensure the access to medicines. In order to solve the above problems, based on existing guidelines at home and abroad and the clinical work characteristics of county hospitals, the first clinical pathway in Chinese county for LC diagnosis and treatment (2023 edition) was compiled. This pathway elaborated on the imaging diagnosis, pathological diagnosis, molecular testing, and precision medicine based on histological-pathological types, tumor-node-metastasis (TNM) classification, and molecular classification, developed different diagnosis and treatment processes for different types of LC patients. Simultaneously, according to the actual work situation of county hospitals, the diagnosis and treatment recommendations in clinical scenarios are divided into basic strategies and optional strategies for elaboration. The basic strategies are the standards that county hospitals must meet, while the optional strategies provide more choices for hospitals, which are convenient for county doctors to put into clinical practice. All the recommended diagnostic and treatment plans strictly refer to existing guidelines and consensus, ensuring the scientificity.

[Developing pathology guidelines and consensus: methods and considerations].

Pathological diagnosis is vital in medicine. Developing and implementing high-quality pathology guidelines and consensus can enhance disease diagnosis accuracy and reduce unnecessary misdiagnosis and missed diagnoses. This article will cover the current status of pathology guidelines and consensus, methods for high-quality development, and the distinctions between them. Additionally, it will provide thoughts and suggestions for promoting their development in China.

[Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis].

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

[The association between body mass index and in-hospital major adverse cardiovascular and cerebral events in patients with acute coronary syndrome].

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2), and obese (BMI≥30.0 kg/m2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively (P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group (OR=1.30, 95%CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

[Preliminary insights into the practice of hypoallergenic home visiting program].

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

[Study on reproductive toxicity of nano-cadmium sulfide with different particle sizes on male mice].

Objective: To investigate the reproductive toxicity of cadmium sulfide nanoparticles (Nano-CdS) with different particle sizes on male mice. Methods: In January 2019, 30 SPF grade male mice were randomly divided into a control group, an experimental group[CdS Ⅰ group (particle size approximately 5 nm), and a CdS Ⅱ group (particle size approximately 50 nm) ], with 10 mice in each group. The experimental group was orally gavaged with 100 mg/kg, once a day, while the control group was gavaged with an equal volume of physiological saline for 45 consecutive days. After 45 days, levels of cadmium accumulation in testis were determined directly by AAS, deformity and testicular histopathological changes were also observed. Serum testosterone levels were measured by enzyme-linked immunosorbentassay (ELISA), expression levels of P450scc, 17ß-HSD and P450c17 mRNA were determined by real-time PCR. P450c17 protein was determinated by Western Blot. Results: The histopathological results showed that the testes of the experimental group mice showed varying degrees of damage; Ultrastructural observation showed that the ultrastructure of mouse testicular cells in each experimental group showed varying degrees of mitochondrial expansion and disappearance of cristae, as well as irregular nuclear membranes. The degree of damage in CdS Ⅰ group was milder than that in CdS Ⅱ group. Compared with the control group, the cadmium content in the testes of the CdS Ⅰ and CdS Ⅱ groups significantly increased (P=0.001, 0.001), and the CdS Ⅱ group was higher than the CdS Ⅰ group (P=0.001). Compared with the control group, the levels of testosterone in the CdS Ⅰ and CdS Ⅱ groups decreased with statistical significance (P=0.001, 0.001). Real time fluorescence quantitative PCR results showed that compared with the control group, the experimental group's P450scc, 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly reduced, with statistically significant differences (P=0.001, 0.001, 0.001), and CdS Ⅱ group 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly lower than those of CdS Ⅰ group (P=0.001, 0.036). The Western Blot assay results showed that the expression levels of P450c17 protein in the testes of CdS Ⅰ and CdS Ⅱ groups of mice were significantly reduced, with statistical significance (P=0.001, 0.001) ; And the CdS Ⅱ group was significantly lower than the CdS Ⅰ group (P=0.001). According to Spearman correlation analysis, testosterone levels are correlated with P450scc, P450c17, 17ß-HSD mRNA. There is a highly positive correlation between 17ß-HSD mRNA levels, with statistically significant differences (r(s)=0.88, 0.80, 0.70, P=0.001, 0.001, 0.004) . Conclusion: Nano cadmium sulfide may induce reproductive toxicity by reducing the expression levels of key enzyme genes and enzyme protein activity in testosterone and its synthesis in mice, and the CdS Ⅱ group has a stronger toxic effect.

Comparison of the Efficacy and Safety of Perioperative Immunochemotherapeutic Strategies for Resectable Non-small Cell Lung Cancer: a Systematic Review and Network Meta-analysis.

AIMS: The aim of this network meta-analysis was to elucidate the efficacy and safety of various immune checkpoint inhibitors (ICIs) used in combination with chemotherapy for the treatment of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Data from randomised controlled trials comparing perioperative ICI-chemotherapy and chemotherapy alone were acquired from the EMBASE, Web of Science, Cochrane Library databases, PubMed, and meeting abstracts from inception until August 2023. The endpoints for this analysis were pathological complete response, event-free survival and treatment-related adverse events of any grade or adverse events of grade 3 or higher. RESULTS: In total, six randomised controlled trials with 2538 NSCLC patients were selected for this network meta-analysis. Compared with other ICIs, toripalimab + chemotherapy demonstrated increased pathological complete response rates and prolonged event-free survival in NSCLC. In patients with negative/low PD-L1 expression or squamous cell pathology, toripalimab + chemotherapy was the most effective regimen. In contrast, nivolumab + chemotherapy was preferable for patients with high PD-L1 expression or non-squamous cell pathology. Among the analysed regimens, toripalimab + chemotherapy presented the highest risk of adverse events of any grade, whereas nivolumab + chemotherapy showed the highest risk of grade 3-4 adverse events. Conversely, durvalumab + chemotherapy exhibited the lowest risk of grade 3-4 adverse events. CONCLUSIONS: Among the evaluated perioperative immunochemotherapy regimens, toripalimab + chemotherapy indicated a significantly increased survival benefit for most resectable NSCLC patients. However, for high PD-L1 expression and non-squamous NSCLC patients, nivolumab + chemotherapy provided the most potent outcomes. Perioperative durvalumab + chemotherapy is a relatively safe treatment. The findings of this investigation are expected to assist clinicians in making informed decisions among promising treatment options.

[Xinfeng Capsule alleviates interleukin-1ß-induced chondrocyte inflammation and extracellular matrix degradation by regulating the miR-502-5p/TRAF2/NF-κB axis].

OBJECTIVE: To investigate the mechanism that mediates the inhibitory effect of Xinfeng Capsule (XFC) on interleukin (IL)-1ß-induced impairment of chondrocytes. METHODS: XFC-medicated serum was collected from SD rats with XFC gavage, and its optimal concentration for chondrocyte treatment was determined using Cell Counting Kit-8 assay and flow cytometry. Dual luciferase reporter analysis was performed to analyze the targeting relationship between miR-502-5p and TRAF2. In cultured human chondrocytes induced with IL-1ß, the effects of transfection with miR-502-5p inhibitor and XFC-medicated serum, alone or in combination, on expression levels of IL-1ß, tumor necrosis factor-α (TNF-α), IL-4, and IL-10 were examined with ELISA, and the changes in the expressions of collagen type Ⅱ alpha 1 (COL2A1), matrix metalloproteinase 13 (MMP13), adisintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and miR-502-5p/TRAF2/NF-κB axis gene expression were detected using RT-qPCR, Western blotting, and immunofluorescence assay. RESULTS: In cultured human chondrocytes, treatment with IL-1ß significantly decreased the cell viability, increased cell apoptosis rate, lowered miR-502-5p, IL-4, IL-10, and COL2A1 expressions, and enhanced IL-1ß, TNF-α, ADAMTS5, MMP13, TRAF2, and NF-κB p65 expressions (P < 0.05), and these changes were significantly improved by treatment with XFC-medicated serum at the optimal concentration of 20% (P < 0.05). Transfection of the chondrocytes with miR-502-5p inhibitor resulted in elevated expressions of IL-1ß, TNF-α, ADAMTS5, MMP13, TRAF2, and NF-κB p65 and lowered expressions of miR-502-5p, IL-4, IL-10, and COL2A1, and XFC-medicated serum obviously reversed the effects of miR-502-5p inhibitor. CONCLUSION: XFC can inhibit IL-1ß-induced inflammatory response and ECM degradation in cultured human chondrocytes possibly by regulating the miR-502-5p/TRAF2/NF-κB axis.

Clinical pharmacist intervention in contraindications of the co-administration of cefoperazone and ambroxol hydrochloride injection.

BACKGROUND: Clinical pharmacists identified contraindications in two cases concerning the co-administration of cefoperazone and ambroxol hydrochloride injection, prompting a thorough investigation. CASE PRESENTATION: Clinically, two cases of contraindications for the co-administration of cefoperazone and ambroxol hydrochloride injection were discovered. After the intervention and analysis by clinical pharmacists, the possible reason could be the precipitation of free alkali due to the immediate administration of ambroxol after the infusion of cefoperazone. Clinical pharmacists suggested avoiding the co-administration of the two and recommended flushing the intravenous lines with 5% glucose injection or 0.9% sodium chloride injection during intravenous infusion to prevent direct drug interaction causing precipitation, thereby reducing the occurrence of adverse events. No adverse events occurred after the intervention, and no harm was caused to the patients. CONCLUSIONS: The co-administration of cefoperazone and ambroxol hydrochloride injection can lead to the precipitation of free alkali, posing a risk of adverse events. Clinical pharmacists' intervention could prevent this interaction. This practice has been shown to be effective, with no subsequent adverse events reported.

Clinical study of tirofiban compared to low molecular weight heparin in the antithrombotic treatment of progressive pontine infarction.

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.

A multi-omics analysis reveals vitamin D supplementation since childhood modulates molecules for signal transductions in the mouse striatum.

Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.

Dietary supplementation of proteases on growth performance, nutrient digestibility, blood characteristics and gut microbiota of growing pigs fed sorghum-based diets.

Low-tannin sorghum is an excellent energy source in pig diets. However, sorghum contains several anti-nutritional factors that may have negative effects on nutrient digestibility. The impacts of proteases on growth performance, nutrient digestibility, blood parameters, and gut microbiota of growing pigs fed sorghum-based diets were studied in this study. Ninety-six pigs (20.66 ± 0.65 kg BW) were allocated into three groups (eight pens/group, four pigs/pen): (1) CON (control diet, sorghum-based diet included 66.98% sorghum), (2) PRO1 (CON + 200 mg/kg proteases), (3) PRO2 (CON + 400 mg/kg proteases) for 28 d. No differences were observed in growth performance and apparent total tract digestibility (ATTD) of nutrients between CON and PRO1 groups. Pigs fed PRO2 diet had increased (P < 0.05) BW on d 21 and 28, and increased (P < 0.05) average daily gain during d 14-21 and the overall period compared with pigs fed CON diet. In addition, pigs fed PRO2 diet had improved (P < 0.05) ATTD of gross energy, CP, and DM compared with pigs fed CON and PRO1 diets. Pigs fed PRO2 diet had lower (P < 0.05) plasma globulin (GLB) level and higher (P < 0.05) plasma glucose, albumin (ALB) and immunoglobulin G levels, and ALB/GLB ratio than pigs fed CON and PRO1 diets. Furthermore, pigs fed PRO2 diet had decreased (P < 0.05) the relative abundance of Acidobacteriota at the phylum level and increased (P < 0.05) the relative abundance of Prevotella_9 at the genus level. The linear discriminant analysis effect size analysis also showed that pigs fed PRO2 diet had significantly enriched short-chain fatty acid-producing bacteria, such as Subdoligranulum and Parabacteroides. In conclusion, protease supplementation at 400 mg/kg improved the growth performance of growing pigs fed sorghum-based diets, which may be attributed to the improvement of nutrient digestibility, host metabolism, immune status and associated with the altered gut microbiota profiles.

[Prevalence of frailty and related factors in middle-aged and elderly people in island and mountainous areas of Taizhou, Zhejiang Province].

Objective: To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province. Methods: Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty. Results: A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (aOR=1.55,95%CI: 1.07-2.25,P=0.019). In island area, older age (60-74 years:aOR=2.52,95%CI: 1.56-4.13; ≥75 years:aOR=11.65,95%CI:5.38-26.70), being women (aOR=1.94,95%CI: 1.20-3.17), suffering from depression (aOR=1.09,95%CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: aOR=1.74,95%CI:1.04-2.94;≥75 years: aOR=4.78,95%CI:2.45-9.50). Polydrug use (aOR=2.08,95%CI: 1.14-3.80) and suffering from depression (aOR=1.10,95%CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: aOR=0.40,95%CI: 0.21-0.75; senior high school and technical secondary school: aOR=0.29,95%CI: 0.15-0.53; college or above:aOR=0.22,95%CI: 0.11-0.42). Conclusions: The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.

[A randomized controlled trial on the effect of exercise prescription based on a progressive mode in treating elderly patients with lower limb dysfunction after deep burns].

Objective: To explore the effect of exercise prescription based on a progressive mode in treating elderly patients with lower limb dysfunction after deep burns. Methods: A randomized controlled trial was conducted. From January 2021 to January 2023, 60 elderly patients with lower limb dysfunction after deep burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University. The patients were divided into conventional rehabilitation group (30 cases, 17 males and 13 females, aged (65±3) years) and combined rehabilitation group (30 cases, 16 males and 14 females, aged (64±3) years) according to the random number table. For patients in both groups, the red-light treatment was started after the lower limb wounds healed or when the total area of scattered residual wounds was less than 1% of the total body surface area. After 2 weeks of red-light treatment, the patients in conventional rehabilitation group were given conventional rehabilitation treatments, including joint stretching, resistance, and balance training; in addition to conventional rehabilitation treatments, the patients in combined rehabilitation group were given exercise prescription training based on a progressive mode three times a week, mainly including dumbbell press, Bobath ball horizontal support, and high-level pulldown trainings. The training time for patients in both groups was 12 weeks. Before training (after 2 weeks of red-light treatment) and after 12 weeks of training, the upper limb and lower limb motor functions of the patients were evaluated using the simple Fugl-Meyer scale, the physical fitness of patients was evaluated using the simple physical fitness scale, and the patient's risk of falling was evaluated by the time consumed for the timed up and go test. The adverse events of patients that occurred during training were recorded. After 12 weeks of training, a self-designed satisfaction survey was conducted to investigate patients' satisfaction with the training effect. Data were statistically analyzed with independent sample t test, paired sample t test, Mann-Whitney U test, Wilcoxon signed rank test, and chi-square test. Results: Before training, the scores of upper limb and lower limb motor functions of patients between the two groups were similar (P>0.05). After 12 weeks of training, the scores of upper limb motor function of patients in conventional rehabilitation group and combined rehabilitation group were significantly higher than those before training (with t values of -11.42 and -13.67, respectively, P<0.05), but there was no statistically significant difference between the two groups (P>0.05). The score of lower limb motor function of patients in combined rehabilitation group was 28.9±2.6, which was significantly higher than 26.3±2.6 in conventional rehabilitation group (t=-3.90, P<0.05), and the scores of lower limb motor function of patients in conventional rehabilitation group and combined rehabilitation group were significantly higher than those before training (with t values of -4.14 and -6.94, respectively, P<0.05). Before training, the individual and total scores of physical fitness of patients between the two groups were similar (P>0.05). After 12 weeks of training, the balance ability score, walking speed score, chair sitting score, and total score of physical fitness of patients in conventional rehabilitation group and combined rehabilitation group were significantly increased compared with those before training (with Z values of -4.38, -3.55, -3.88, -4.65, -4.58, -4.68, -4.42, and -4.48, respectively, P<0.05), and the balance ability score, walking speed score, chair sitting score, and total score of physical fitness of patients in combined rehabilitation group were significantly increased compared with those in conventional rehabilitation group (with Z values of -3.93, -3.41, -3.19, and -5.33, P<0.05). Before training, the time consumed for the timed up and go test for patient's risk of falling in the two groups was close (P>0.05). After 12 weeks of training, the time consumed for the timed up and go test for patient's risk of falling in combined rehabilitation group was (28.0±2.1) s, which was significantly shorter than (30.5±1.8) s in conventional rehabilitation group (t=4.94, P<0.05). Moreover, the time consumed for the timed up and go test for patient's risk of falling in both conventional rehabilitation group and combined rehabilitation group was significantly shorter than that before training (with t values of 14.80 and 15.86, respectively, P<0.05). During the training period, no adverse events such as muscle tissue strain, edema, or falling occurred in any patient. After 12 weeks of training, the satisfaction score of patients with the training effect in combined rehabilitation group was 13.5±1.2, which was significantly higher than 8.5±1.4 in conventional rehabilitation group (t=21.78, P<0.05). Conclusions: The exercise prescription training based on a progressive mode can significantly promote the recovery of lower limb motor function and physical fitness of elderly patients with lower limb dysfunction after deep burns, and effectively reduce the patient's risk of falling without causing adverse events during the training period, resulting in patient's high satisfaction with the training effect.