Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective To compare the benefits and drawbacks of primary patch expansion versus pericardial tube right ventricular-pulmonary artery connection in patients diagnosed with pulmonary atresia with ventricular septal defect (PA/VSD). Methods A retrospective study was conducted on patients diagnosed with PA/VSD who underwent primary right ventricular-pulmonary artery connection surgery at our center between 2010 and 2020. Patients were categorized into two groups based on the type of right ventricular-pulmonary artery connection: a pericardial tube group and a patch expansion group. Clinical data and imaging findings were compared between the two groups. Results A total of 51 patients were included in the study, comprising 31 males and 20 females, with a median age of 12.57 (4.57, 49.67) months. The pericardial tube group included 19 patients with a median age of 17.17 (7.33, 49.67) months, while the patch expansion group consisted of 32 patients with a median age of 8.58 (3.57, 52.72) months. In both groups, the diameter of pulmonary artery, McGoon index, and Nakata index significantly increased after treatment (P<0.001). However, the pericardial tube group exhibited a longer extracorporeal circulation time (P<0.001). The reoperation rate was notably high, with 74.51% of patients requiring further surgical intervention, including 26 (81.25%) patients in the patch expansion group and 12 (63.16%) patients in the pericardial tube group. No statistical differences were observed in long-term cure rates or mortality between the two groups (P＞0.005). Conclusion In patients with PA/VSD, both patch expansion and pericardial tube right ventricular-pulmonary artery connection serve as effective initial palliative treatment strategies that promote pulmonary vessel development and provide a favorable foundation for subsequent radical operations. However, compared to the pericardial tube approach, the patch expansion technique is simpler to perform and preserves some intrinsic potential for pulmonary artery development, making it the preferred procedure.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Objective:To investigate the efficacy of modified fire dragon moxibustion in patients with phlegm-dampness obesity and prediabetes.Methods:From April 2024 to March 2025, 62 patients with phlegm-dampness obesity and prediabetes who visited the Department of Endocrinology of Ningbo Hospital of Traditional Chinese Medicine were selected as study subjects using convenience sampling. The study subjects were divided into an intervention group and a control group using a random number table method, with 31 cases in each group. Control group received conventional medication, dietary and exercise management, while intervention group received modified fire dragon moxibustion in addition to conventional medication, dietary and exercise management. Both groups underwent the intervention for 60 days. Fasting blood glucose (FBG) , glycated hemoglobin (HbA1c) , triglycerides (TG) , body mass index, fasting insulin (FINS) , and homeostatic model assessment of insulin resistance (HOMA-IR) were compared between the two groups before and after intervention.Results:After intervention, the body mass index, FBG, HbA1c, FINS, and HOMA-IR of intervention group were lower than those of control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified fire dragon moxibustion can reduce the body mass index, improve glucose metabolism indicators, and FINS and HOMA-IR levels in patients with phlegm-dampness obesity and prediabetes.

Objective:To investigate the role of a modified positioning device in improving image quality and diagnostic efficacy for thyroid cancer in contrast-enhanced neck CT imaging.Methods:This prospective cross-sectional study included 137 patients with pathologically confirmed thyroid lesions who underwent contrast-enhanced neck CT at Zhangzhou Affiliated Hospital of Fujian Medical University from January to April 2024. Patients scanned in January and February (modified positioning group, n=62) underwent scanning using the modified positioning device, whereas those scanned in March and April (traditional positioning group, n=75) underwent scanning with conventional positioning. The estimated volume CT dose index (CTDI vol) in the thyroid region was recorded. Subjective image quality for thyroid and neck regions was evaluated using a 5-point Likert scale. Diagnostic assessments for thyroid cancer, capsule invasion, and lymph node metastasis were independently conducted by one junior radiologist and one senior radiologist using a 5-point scoring system, with scores≥3 considered positive diagnoses. The differences of CTDI vol and image quality scores between the 2 groups were compared using Mann-Whitney U test. The diagnostic performance was evaluated by the receiver operating characteristic curve analysis. Results:The estimated CTDI vol values for the thyroid region were significantly lower in the modified positioning group compared to the traditional positioning group [11.20 (8.37, 13.56) vs. 12.46 (10.10, 19.43) mGy, Z=1.99, P=0.026]. Subjective image quality scores for thyroid and neck regions were significantly higher in the modified positioning group than in the traditional positioning group (all P<0.001). For thyroid cancer diagnosis by the senior radiologist, the modified positioning group had a significantly higher area under the curve (AUC) of 0.842 (95% CI 0.728-0.956) compared to the traditional positioning group (AUC=0.666,95% CI 0.554-0.777, Z=2.17, P=0.031). No significant differences were observed in diagnostic performance between the junior and senior radiologists for thyroid cancer, capsule invasion, and lymph node metastasis in other subgroup comparisons (all P>0.05). Conclusion:The modified positioning device using in contrast-enhanced neck CT imaging can improve image quality and diagnostic efficacy for thyroid cancer while reducing radiation exposure to the thyroid gland.

Objective To analyze the application effect of size-specific dose estimate(SSDE)in radiation dose and images quality of coronary CT angiography(CCTA).Methods A retrospective study was conducted on 56 patients undergoing CCTA at the First Affiliated Hospital of Chongqing Medical University between February 2022 and February 2025.These patients were assigned to observation group(SSDE injection),while another 56 patients undergoing CCTA during the same period were enrolled as routine group(traditional injection).The two groups were compared for coronary enhancement value,images quality score,objective parameters of images quality[image noise,CT value,contrast to noise ratio(CNR),signal to noise ratio(SNR)],radiation dose parameters[dose-length product(DLP),CT dose index volume(CTDIvol),effective dose(ED)],anteroposterior diameter,left-right diameter and fsize.Results The CCTA image quality score and coronary enhancement value in observation group were significantly higher than those in routine group(P<0.05).Compared with routine group,observation group had higher CT value,CNR,and SNR,as well as lower image noise(P<0.05).The CTDIvol,ED,DLP and SSDE of observation group were lower than those of routine group(P<0.05).The?size in observation group was smaller,while anteroposterior diameter and left-right diameter were longer than those in routine group(P<0.05).Conclusion The application of SSED protocol in CCTA scanning can effectively improve radiation dose and images quality.

OBJECTIVE To evaluate the economic burden of the intensive care unit(ICU)patients due to hospital-associated multidrug-resistant organisms(MDROs)infections based on propensity score matching(PSM)so as to provide evidence-based bases for prevention and control of hospital-associated MDROs infection and improvement of utilization efficiency of medical resources.METHODS A total of 2118 patients who were hospitalized in Zibo Central Hospital from Jan.1,2023 to Dec.31,2024 and conformed to the inclusion and exclusion criteria were re-cruited as the research subjects.The patients with hospital-associated MDROs infections were matched in a 1∶1 ratio by PSM(with the clamp value 0.02).Totally 309 pairs were successfully matched.The length of hospital stay and the costs were observed and compared between the MDROs group and the non-MDROs group.RESULTS The MDROs group was with the length of hospital stay 14.00 days longer than the non-MDROs group after the matching(Z=-5.750,P＜0.001),with the total cost of hospitalization increased by 91,420.84 yuan(Z=-8.271,P＜0.001).With the respect to the medical treatment expenses,the expenses of the MDROs group were higher than those of the non-MDROs group,covering the cost of medical service,therapeutic procedures,nursing,western medicine and TCM,and there were significant differences(P＜0.05).Among the differences in the costs between the two groups,the difference in the cost of western medicine was the most signif-icant(22,182.91 yuan),followed by the cost of clinical laboratory test for diagnosis(19,529.60 yuan)and the cost of therapeutic procedures(16,333.50 yuan).CONCLUSIONS The hospital-associated MDROs infections may lead to the extension of hospital stay length of the ICU patients,which then increases the economic burden.There-fore,it is necessary to strengthen the multidisciplinary collaboration and formulate corresponding measures so as to reduce the risk of such infections among the ICU patients.

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.