Objective: To investigate whether Tuina alleviates fibrotic symptoms in myofascial trigger points (MTrPs) by regulating transforming growth factor (TGF)-β1/Smad3 signaling pathway, thereby deactivating these points. Methods: This study comprised two experimental phases. In phase 1, 27 specific pathogen-free (SPF) grade female Sprague-Dawley (SD) rats were randomized into three groups: control 1, model 1, and Tuina 1 groups. Model 1 and Tuina 1 groups underwent an 8-week MTrPs modeling protocol involving blunt impact and eccentric exercise. After successful modeling, rats in Tuina 1 group received manual pressing on nodules or cord-like taut bands on the medial aspect of the left hindlimb. Pain sensitivity and tissue stiffness were evaluated via pressure pain threshold (PPT) and soft tissue tension (STT). Muscle histopathology and fibrosis were observed using hematoxylin and eosin (HE) and Masson staining. Inflammatory factors in muscle were measured by enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) and Western blot (WB) were used to detect the expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ, and TGF-β1. In phase 2, 45 SPF female SD rats were randomized into five groups: control 2, model 2, Tuina 2, TGF-β1 inhibitor (TI), and Tuina + TGF-β1 agonist (Tuina + TA) groups. All groups except control 2 underwent standardized MTrPs modeling. Rats in Tuina 2 group received consistent pressing manipulation. TI group received intraperitoneal injections of oxymatrine, while Tuina + TA group received intraperitoneal injections of SRI-011381 hydrochloride followed by the same pressing protocol as Tuina 2 group. WB was used to detect the expression of collagen I, collagen III, TGF-β1, and phosphorylated-Smad3 (p-Smad3)/Smad3. Results: In phase 1, Tuina significantly improved PPT and STT in MTrPs of rats (P < 0.01), reversed pathological damages including disorganized muscle fiber arrangement, abnormal myocyte morphology, and exacerbated fibrosis. In addition, in MTrPs of rats in model 1 group, expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and fibrosis markers (α-SMA, collagen I, and collagen III) were upregulated, and all exhibited a significant downward trend after Tuina intervention (P < 0.05 or P < 0.01). This indicates that the therapeutic effects of Tuina are directly associated with reduced local inflammation and fibrosis in MTrPs. In phase 2, compared with model 2 group, rats in TI and Tuina 2 groups had decreased expression levels of TGF-β1 and p-Smad3/Smad3 in MTrPs, alongside reduced levels of inflammatory factors (IL-1β, IL-6, NF-κB, and TNF-α) and fibrosis markers (α-SMA, collagen I, and collagen III) (P < 0.05 or P < 0.01). When co-administered with TGF-β1 agonist, the therapeutic effects of Tuina were significantly attenuated, with rebounded TGF-β1 expression and p-Smad3/Smad3 in local MTrPs, and fibrosis and inflammatory responses were re-exacerbated (P < 0.05 or P < 0.01). Conclusion Tuina can effectively reduce inflammatory responses and fibrosis in MTrPs tissue, and its mechanism is closely related to the inhibition of the TGF-β1/Smad3 signaling pathway, which plays a critical role in Tuina-mediated regulation of MTrPs fibrosis.

Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective:To discuss the relationship between the systolic blood pressure (SBP) circadian rhythm and blood pressure variability (BPV) and the left ventricular ejection fraction (LVEF) among 178 patients with hypertension.Methods:This article was a retrospective study. Totally 178 patients with hypertension from January 2020 to January 2022 were selected based on incorporated basis. 24-hour dynamic blood pressure monitoring and echocardiography examination were performed. Data such as patients' SBP circadian rhythm, BPV, heart ultrasound heart dynamic maps were collected, and the relationship between SBP circadian rhythm and BPV and their LVEF was explored.Results:Among the 178 patients, the decreased proportion of SBP circadian rhythm>the proportion of existed SBP circadian rhythm>the proportion of inverted SBP circadian rhythm>the proportion of disappearance of SBP circadian rhythm; patients with disappearance of SBP circadian rhythm were the youngest (63.8 ± 14.5) years old, and patients with inverted SBP circadian rhythm were the oldest (71.5 ± 9.4) years old ( P<0.05); the 24-hour systolic blood pressure standard deviation of SBP circadian rhythm was observed in patients with (13.1 ± 2.8) mmHg

Background and Aims:Medullary thyroid carcinoma(MTC)is an aggressive malignancy that is frequently associated with cervical lymph node metastasis,significantly affecting patient prognosis.However,the risk factors for lateral cervical lymph node metastasis(LLNM)in MTC remain inconclusive.This study aims to identify the risk factors associated with LLNM in MTC patients,in order to inform individualized surgical decision-making.Methods:The clinicopathologic data of 242 patients with MTC who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from 2011 to 2019 were retrospectively collected.The relationships between preoperative tumor markers,including calcitonin and carcinoembryonic antigen(CEA),and LLNM were evaluated.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for LLNM.Results:Preoperative calcitonin level was significantly associated with tumor diameter,the number of lymph node metastases,and the extent of lymph node involvement,while preoperative CEA level was significantly associated with tumor diameter(all P<0.05).The area under the ROC curve for preoperative calcitonin in diagnosing LLNM was 0.750(P=0.000),with an optimal cutoff value of 266.00 ng/L(sensitivity 0.854,specificity 0.577).The diagnostic value of preoperative CEA for LLNM was limited.Univariate analysis showed that sex,extracapsular extension,T stage,central lymph node metastasis(CLNM),bilateral lesions,preoperative calcitonin,tumor diameter,and multifocality were significantly associated with LLNM in MTC patients(all P<0.05).Multivariate analysis revealed that CLNM(OR=17.645,95%CI=7.728-40.290)and preoperative calcitonin≥266.00 ng/L(OR=7.832,95%CI=3.132-19.582)were independent risk factors for LLNM.Conclusion:CLNM and elevated preoperative calcitonin level are closely associated with LLNM in patients with MTC.The combination of these two indicators may help identify high-risk patients for LLNM,thereby and promoting individualized and precise treatment strategies for MTC.

Objective To investigate the effects of TEK receptor tyrosine kinase(Tie2)L914F mutation on the biological behavior of vascular endothelial cells and the changes of related signaling pathways in patients with venous malformations.Methods Gene sequen-cing was used to detect Tie2-L914F mutations in venous malformations.HE staining and immunohistochemical staining were used to de-tect the expression of platelet derived growth factor subunit B gene(PDGFB)and α-smooth muscle actin(α-SMA)in venous malfor-mations caused by the mutation.Lentivirus overexpressing Tie2-wild type(Tie2-WT),Tie2-L914F and Tie2-GFP(green fluorescent protein,GFP)infected human umbilical vein endothelial cells(HUVECs).Real-time fluorescence quantitative PCR was used to detect the expression level of Tie2 in endothelial cells expressing exogenous Tie2 and Flag-tagged protein Tie2 protein was detected by western blotting to verify transfection efficiency.The proliferation,apoptosis,migration and tube-forming ability of the cells were determined by CCK-8,flow cytometry,Transwell migration assay and Matrigel matrix gel tube-forming assay.Western blotting was used to detect the expression levels of Protein Kinase B(PKB/AKT),FOXO1 and their phosphorylation,and the expression level of PDGFB was detec-ted by ELISA.Results The number of patients with venous malformations with L914F mutations was about 33.3％.HE and immuno-histochemical staining showed that the expressions of PDGFB and α-SMA were significantly down-regulated in venous malformation tis-sues with Tie2-L914F mutation,and were positively correlated with the decrease in cell coverage of the tube wall.Compared with Tie2-WT endothelial cells,the apoptosis number of Tie2-L914F endothelial cells was significantly reduced,while the proliferation and mi-gration ability was significantly increased,and the tube-forming ability was significantly decreased.Western blotting and ELISA showed that the phosphorylation levels of AKT and FOXO1 downstream of Tie2 signaling pathway in endothelial cells expressing Tie2-L914F were significantly increased,and the expression level of PDGFB was significantly decreased.Conclusion In venous malformations,Tie2-L914F mutation may downregulate the expression of PDGFB through AKT signaling pathway,which affects the biological behavior of vascular endothelial cells.

Objective:To observe the clinical effect of the new type of lung body projection flashlight for percussion back in patients with cerebral hemorrhage, so as to promote patient lung rehabilitation, reduce pulmonary complications, and improve prognosis.Methods:Adopting a randomized controlled trial method, a total of 102 patients with cerebral hemorrhage who were hospitalized in the Department of Neurosurgery of The First Hospital of Jiaxing from January 2022 to December 2023 and their caregivers were selected as the research objects by convenience sampling method. The patients were divided into the control group (51 cases) and the observation group (51 cases) by the random number table method. The control group received traditional back tapping on the basis of routine nursing and back tapping guidance. The observation group used a new type of lung body projection flashlight for percussion back to assist in back tapping nursing and health guidance on the basis of routine nursing.The incidence of pulmonary infection, white blood cell count, levels of hypersensitive C-reactive protein and procalcitonin, the quality of discharge guidance, the scores of satisfaction of patients, and the assessment score of caregivers′ percussion back skills were evaluated in the two groups.Results:Finally, a total of 49 patients were enrolled in the observation group, including 38 males and 11 females, aged (67.08 ± 11.05) years old. A total of 49 patients were enrolled in the control group, including 31 males and 18 females, aged (68.84 ± 10.46) years old. There were 8 males and 41 females, aged (58.00 ± 8.17) years old in the caregivers of the observation group. There were 6 males and 43 females, aged (57.57 ± 9.15) years old in the caregivers of the observation group. The incidence of pulmonary infection in the observation group was 28.6% (14/49), which was lower than that in the control group 32.7% (16/49), and the difference was not statistically significant ( P>0.05). There was no significant difference in the level of white blood cell count, hypersensitive C-reactive protein and procalcitonin between the two groups when the time of pulmonary infection was diagnosed and after 2 weeks of treatment ( P>0.05). The levels of white blood cell count, hypersensitive C-reactive protein and procalcitonin after 1 week of treatment were (7.97 ± 1.30)×10 9/L, (30.71 ± 11.96) mg/L, 0.04(0.02, 0.07) μg/L in the observation group, which were all lower than those in the control group (9.46 ± 2.16) × 10 9/L, (58.34 ± 48.96) mg/L, 0.09(0.04, 0.20) μg/L, and the differences were statistically significant ( t=5.06, 4.22, Z=1.98, all P<0.05). The total score of discharge guidance quality, obtained content, guidance skills and effect scores were (134.94 ± 7.34), (47.80 ± 2.86), (87.14 ± 5.98) points in the observation group, which were significantly higher than those in the control group (117.04 ± 7.04), (39.80 ± 3.15), (77.24 ± 5.60) points, and the differences were statistically significant ( t=12.32, 13.15, 8.46, all P<0.05). The scores of the satisfaction of patients including six aspects(operation convenience, precise positioning, goal orientation, operation specification, nursing confidence and mission satisfaction) in the observation group were 91.84%(45/49), 95.92%(47/49), 91.84%(45/49), 93.88%(46/49), 91.84%(45/49), 97.96%(48/49), which were higher than those in the control group 73.47%(36/49), 57.14%(28/49), 53.06%(26/49), 67.35%(33/49), 73.47%(36/49), 81.63%(40/49), and the differences were statistically significant ( χ2 values were 5.76-20.51, all P<0.05). The assessment score of percussion skills of caregivers in the observation group was (79.55 ± 3.98) points, which was significantly higher than that in the control group (75.35 ± 4.94) points, and the difference was statistically significant ( t=4.64, P<0.05). Conclusions:The clinical application of the new type of lung body projection flashlight for percussion back in patients with cerebral hemorrhage can achieve accurate and standardized percussion back to promote the improvement of pulmonary infection and improve the skill level of caregivers of cerebral hemorrhage patients, as well as improve the quality of discharge guidance and the satisfaction of patients.

Background and Aims:Medullary thyroid carcinoma(MTC)is an aggressive malignancy that is frequently associated with cervical lymph node metastasis,significantly affecting patient prognosis.However,the risk factors for lateral cervical lymph node metastasis(LLNM)in MTC remain inconclusive.This study aims to identify the risk factors associated with LLNM in MTC patients,in order to inform individualized surgical decision-making.Methods:The clinicopathologic data of 242 patients with MTC who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from 2011 to 2019 were retrospectively collected.The relationships between preoperative tumor markers,including calcitonin and carcinoembryonic antigen(CEA),and LLNM were evaluated.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for LLNM.Results:Preoperative calcitonin level was significantly associated with tumor diameter,the number of lymph node metastases,and the extent of lymph node involvement,while preoperative CEA level was significantly associated with tumor diameter(all P<0.05).The area under the ROC curve for preoperative calcitonin in diagnosing LLNM was 0.750(P=0.000),with an optimal cutoff value of 266.00 ng/L(sensitivity 0.854,specificity 0.577).The diagnostic value of preoperative CEA for LLNM was limited.Univariate analysis showed that sex,extracapsular extension,T stage,central lymph node metastasis(CLNM),bilateral lesions,preoperative calcitonin,tumor diameter,and multifocality were significantly associated with LLNM in MTC patients(all P<0.05).Multivariate analysis revealed that CLNM(OR=17.645,95%CI=7.728-40.290)and preoperative calcitonin≥266.00 ng/L(OR=7.832,95%CI=3.132-19.582)were independent risk factors for LLNM.Conclusion:CLNM and elevated preoperative calcitonin level are closely associated with LLNM in patients with MTC.The combination of these two indicators may help identify high-risk patients for LLNM,thereby and promoting individualized and precise treatment strategies for MTC.

Non-small cell lung cancer(NSCLC)is one of the most common and deadly malignant tumors worldwide,with surgical resection being the primary treatment for early-stage NSCLC.Tumor spread through air spaces(STAS)is a novel pattern of tumor dissemination into the air spaces in the lung.Its occurrence after sublobar resection is closely associated with recurrence and distant metastasis,making its con-sideration a vital factor in surgical strategy selection and prognostic evaluation.Patients with STAS-positive status exhibit significantly higher postoperative recurrence rates than do STAS-negative patients,with molecular mechanisms involving tumor microenvironment remodeling,specific genetic mutations,and epithelial-mesenchymal transition(EMT).Imaging techniques including computed tomography(CT)and positron emission tomography/CT have shown potential for preoperative STAS prediction,although their accuracy and practicality require improvement.This paper reviews the definition,pathological characteristics,and related mechanisms of STAS,with a focus on surgical ap-proach selection for STAS-positive patients and its role in cancer recurrence after sublobar resection of early-stage NSCLC.Future research directions include optimization of preoperative diagnostic methods for STAS,exploration of molecular targeted therapies,and development of imaging-based precision prediction models.

Non-small cell lung cancer(NSCLC)is one of the most common and deadly malignant tumors worldwide,with surgical resection being the primary treatment for early-stage NSCLC.Tumor spread through air spaces(STAS)is a novel pattern of tumor dissemination into the air spaces in the lung.Its occurrence after sublobar resection is closely associated with recurrence and distant metastasis,making its con-sideration a vital factor in surgical strategy selection and prognostic evaluation.Patients with STAS-positive status exhibit significantly higher postoperative recurrence rates than do STAS-negative patients,with molecular mechanisms involving tumor microenvironment remodeling,specific genetic mutations,and epithelial-mesenchymal transition(EMT).Imaging techniques including computed tomography(CT)and positron emission tomography/CT have shown potential for preoperative STAS prediction,although their accuracy and practicality require improvement.This paper reviews the definition,pathological characteristics,and related mechanisms of STAS,with a focus on surgical ap-proach selection for STAS-positive patients and its role in cancer recurrence after sublobar resection of early-stage NSCLC.Future research directions include optimization of preoperative diagnostic methods for STAS,exploration of molecular targeted therapies,and development of imaging-based precision prediction models.