Objective:To investigate the predictive value of elevated calprotectin S100A9 (S100A9) concentration during living-donor liver transplantation (LDLT) for early acute lung injury (ALI) in children with biliary atresia.Method:A retrospective analysis was conducted on 280 pediatric patients with biliary atresia who underwent LDLT using hyperreduced left lateral segment grafts at Tianjin First Central Hospital between January 2019 and January 2021. Based on intraoperative serum S100A9 levels at 30 minutes after graft reperfusion, patients were divided into the high S100A9 group (≥9.05 μg/L, 141 cases) and the low S100A9 group (<9.05 μg/L, 139 cases). General clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to examine the correlation between S100A9 levels and early postoperative ALI. The predictive value of risk factors was assessed using receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) .Result:A total of 280 eligible children were included in the study, with 141 in the high S100A9 group and 139 in the low S100A9 group. The incidence of ALI was significantly higher in the high S100A9 group (31.2%) compared to the low S100A9 group (10.8%). Multivariate regression analysis identified elevated preoperative creatinine levels ( OR=1.191, 95% CI: 1.069~1.321, P=0.002), increased intraoperative S100A9 concentrations ( OR=1.426, 95% CI: 1.272~1.599, P=0.021), and higher intraoperative blood transfusion volume ( OR=0.985, 95% CI: 0.973~0.997, P=0.017) as independent risk factors for postoperative ALI in pediatric LDLT. The predictive value of intraoperative S100A9 levels for ALI was significant, with an AUC of 0.816 (95% CI: 0.758~0.874), a sensitivity of 80.5%, a specificity of 73.7%, and an optimal cutoff value of 9.49 μg/L. Furthermore, preoperative albumin and creatinine levels were found to be correlated with increased intraoperative S100A9 levels. Conclusion:Elevated intraoperative S100A9 levels, increased preoperative creatinine levels, and higher intraoperative blood transfusion volumes are independent risk factors for early ALI following pediatric LDLT. S100A9 levels have strong predictive value for ALI occurrence, highlighting the need for perioperative monitoring and intervention strategies to improve postoperative outcomes.

Objective To construct a nomogram model for predicting pulmonary hemorrhage associated with the positioning of pulmonary nodules with the new four-hook positioning needle based on clinical-CT imaging features and evaluate its predictive efficacy.Methods We made a retrospective analysis of the clinical,imaging and pathological data of 449 patients with pulmonary nodules positioned by the new four-hook positioning needle.According to the random number table method(7∶3),they were divided into a training set of 314 cases and a validation set of 135 cases.Each data set was further divided into positive group and negative group for pulmonary hemorrhage according to the presence or absence of pulmonary hemorrhage.We evaluated the CT imaging features of pulmonary nodules,including nodule nature(pure ground-glass density,mixed ground-glass density,solid nodule),nodule diameter,distance from the nodule to the pleural surface(hereinafter referred to as length),nodule positioning time,and association with pulmonary hemorrhage.Independent sample t-test,Mann-Whitney U test and x2 test were used to compare the correlations of clinical and CT features of pulmonary nodules with pulmonary hemorrhage.LASSO regression and multivariate Logistic regression were employed to screen the independent risk factors related to pulmonary hemorrhage and construct a nomogram model.The receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the model,and the calibration curve and decision curve were respectively used for the verification of the nomogram model and evaluation of the clinical net benefit.Results The results of LASSO regression showed that the nature of pulmonary nodules,underlying diseases,smoking and length were the characteristic variables related to pulmonary hemorrhage.Based on the minimum akaike information criterion(AIC),the screened characteristic variables were included in the multivariate Logistic backward stepwise regression analysis.The results showed that the nature of pulmonary nodules,underlying diseases,smoking and length were all independent risk factors related to pulmonary hemorrhage.A nomogram was established according to the above independent risk factors and the ROC curve was drawn.The AUC of the training set was 0.86(95％CI:0.80-0.91),and the AUC of the validation set was 0.88(95％CI:0.80-0.96),with no statistically significant difference(P＞0.05).The calibration curve suggested that the predicted values of the nomogram were close to the actual values,and the decision curve analysis showed that the net benefit of the model was good.Conclusion The nomogram model established by combining clinical-CT features such as the nature of pulmonary nodules,underlying diseases,smoking and length can effectively predict pulmonary hemorrhage associated with the positioning of pulmonary nodules with the new four-hook positioning needle.

Objective:To investigate the role of calcium-binding protein S100A9 in acute lung injury induced by hepatic ischemia-reperfusion (HIR) in mice, and to explore its relationship with nuclear factor erythroid 2-related factor 2 (Nrf2).Methods:A total of 12 specific pathogen-free (SPF) male wild-type (WT) and 12 S100A9 knockout (S100A9 KO) C57BL/6J mice aged 6~8 weeks and weighing 20-25 g were randomly divided into four groups using a random number table: WT+Sham group, S100A9 KO+Sham group, WT+HIR group, and S100A9 KO+HIR group ( n=6 per group). The HIR model was established by clamping the portal vein and hepatic artery of the left and median liver lobes for 60 minutes followed by reperfusion. At 6 hours post-reperfusion, mice were anesthetized again, and blood samples were collected from the inferior vena cava. Both lungs were harvested. The lung wet-to-dry (W/D) weight ratio was measured. Hematoxylin and eosin (HE) staining was used to assess histopathological changes and calculate lung injury scores. The levels of inflammatory markers—S100A9, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) —as well as oxidative stress indicators including myeloperoxidase (MPO), reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum and lung tissue were measured. Western blotting was used to assess the expression levels of nuclear and cytoplasmic Nrf2, and cytoplasmic HO-1. Results:Compared with the WT+Sham group, both the WT+HIR and S100A9 KO+HIR groups showed significantly increased lung injury scores, W/D ratio, TNF-α, IL-6, ROS, MPO, and MDA levels (all P<0.05). Compared with the WT+HIR group, the S100A9 KO+HIR group exhibited significantly reduced levels of these indicators (all P<0.05). Moreover, the S100A9 KO+HIR group showed elevated nuclear Nrf2 expression and decreased cytoplasmic Nrf2 expression, accompanied by increased expression of HO-1, Gclm, Gclc, and Nqo1 (all P<0.05). Conclusion:Upregulation of S100A9 is involved in the development of HIR-induced acute lung injury, possibly through inhibition of Nrf2 nuclear translocation.

Objective:To investigate the predictive value of elevated calprotectin S100A9 (S100A9) concentration during living-donor liver transplantation (LDLT) for early acute lung injury (ALI) in children with biliary atresia.Method:A retrospective analysis was conducted on 280 pediatric patients with biliary atresia who underwent LDLT using hyperreduced left lateral segment grafts at Tianjin First Central Hospital between January 2019 and January 2021. Based on intraoperative serum S100A9 levels at 30 minutes after graft reperfusion, patients were divided into the high S100A9 group (≥9.05 μg/L, 141 cases) and the low S100A9 group (<9.05 μg/L, 139 cases). General clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to examine the correlation between S100A9 levels and early postoperative ALI. The predictive value of risk factors was assessed using receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) .Result:A total of 280 eligible children were included in the study, with 141 in the high S100A9 group and 139 in the low S100A9 group. The incidence of ALI was significantly higher in the high S100A9 group (31.2%) compared to the low S100A9 group (10.8%). Multivariate regression analysis identified elevated preoperative creatinine levels ( OR=1.191, 95% CI: 1.069~1.321, P=0.002), increased intraoperative S100A9 concentrations ( OR=1.426, 95% CI: 1.272~1.599, P=0.021), and higher intraoperative blood transfusion volume ( OR=0.985, 95% CI: 0.973~0.997, P=0.017) as independent risk factors for postoperative ALI in pediatric LDLT. The predictive value of intraoperative S100A9 levels for ALI was significant, with an AUC of 0.816 (95% CI: 0.758~0.874), a sensitivity of 80.5%, a specificity of 73.7%, and an optimal cutoff value of 9.49 μg/L. Furthermore, preoperative albumin and creatinine levels were found to be correlated with increased intraoperative S100A9 levels. Conclusion:Elevated intraoperative S100A9 levels, increased preoperative creatinine levels, and higher intraoperative blood transfusion volumes are independent risk factors for early ALI following pediatric LDLT. S100A9 levels have strong predictive value for ALI occurrence, highlighting the need for perioperative monitoring and intervention strategies to improve postoperative outcomes.

Objective To explore the preferences and needs of colorectal cancer patients for"Internet+TCM nursing services",aiming to provide a basis for the improvement of service quality and the formulation of relevant policies,so as to better meet the needs of patients.Methods A total of 189 patients with colorectal cancer who were admitted to a tertiary A Chinese Medicine hospital in Qingdao from September 2023 to July 2024 were selected as the research subjects.A general data questionnaire and Questionnaire on"Internet+Traditional Chinese Medicine Nursing Service"Preference of Colorectal Cancer Patients were used with 6 attributes,including average out-of-pocket cost,nurse qualification,service waiting time,service mode,comprehensiveness of service content,and platform service evaluation,each attribute with 2 to 3 levels.The preference,payment intention of"Internet+TCM nursing services"were analyzed by constructing a mixed Logit model,and the influencing factors of choice preference of different colorectal cancer patients was explored through subgroup analysis.Results Totally 189 questionnaires were sent out,and 156 valid questionnaires were collected,with an effective recovery rate of 82.54％.Among the respondents,112 patients(71.79％)actively accepted"Internet+TCM nursing services",and the attributes of"Internet+TCM nursing services"such as payment fee,service evaluation,service content and nurse qualification had an impact on nursing service preference of colorectal cancer patients(P＜0.05).Based on willingness to pay,the ranking of attributes was service evaluation,service content and nurse qualification.Factors such as education level and the presence of ostomy also affected the preference of"Internet+TCM nursing services"in patients with colorectal cancer(P＜0.05).Conclusion Patients with colorectal cancer prefer"Internet+TCM nursing services",which has an average service cost of 50 yuan per time,excellent platform service evaluation,comprehensive service content,specialized TCM nurses.The preferences and specific characteristics of patients with colorectal cancer can be considered to optimize the allocation of nursing resources and provide services in line with their preferences.

Objective To investigate the efficacy and safety of Linaclotide combined with Simethicone oil and compound polyethylene glycol electrolyte(PEG)for cleansing effect of bowel in patients with constipation.Methods A prospective randomized controlled trial was designed and implemented by single blind method.383 patients with constipation who underwent colonoscopy from April 2023 to August 2024 were enrolled and randomly divided into routine group(128 cases),experimental group A(128 cases)and experimental group B(127 cases).Routine group treated with 3 L PEG,experimental group A treated with 290 μg Linaclotide+2 L PEG and experimental group B treated with 290 μg Linaclotide+30 mL Simethicone+2 L PEG.Bowel preparation effect[Boston bowel preparation scale(BBPS)scores and foaming removal effect],lesion detection rate,first defecation interval,frequency of defecation,the success rate of cecal intubation,the insertion time of colonoscopy,the withdrawal time of colonoscopy,incidence of adverse reactions and willingness to repeat examination of the three groups were compared.Results No statistically significant differences were observed in the BBPS scores among the three groups(P>0.05);The foaming removal effect score in experimental group B was significantly lower than that in routine group and experimental group A,the difference was statistically significant(P<0.05);The total lesion detection rate and polyps detection rate of experimental group B were significantly higher than those of routine group and experimental group A,the differences were statistically significant(P<0.05).The first defecation interval of the routine group was significantly longer than that of experimental group A and experimental group B,the difference was statistically significant(P<0.05);The frequency of defecation was compared among the three groups,and the difference was no statistically significant(P>0.05).The success rate of cecal intubation in the three groups was 100.0%,and the insertion time of colonoscopy was similar,the differences were not statistically significant(P>0.05);The withdrawal time of colonoscopy in experimental group B was significantly shorter than that in routine group and experimental group A,the difference was statistically significant(P<0.05).The incidence of abdominal distension and total adverse reactions in the routine group were higher than those in experimental group A and experimental group B,the differences were statistically significant(P<0.05);The willingness to repeat examination rate of the routine group was significantly lower than that of experimental group A and experimental group B,the differences were statistically significant(P<0.05).Conclusion 290 μg Linaclotide combined with 30 mL Simethicone and 2 L PEG solution regimen has advantages in intestinal preparation for patients with constipation,and can achieve better intestinal cleaning effect than 3 L PEG solution and 290 μg linalopeptide+2 L PEG solution regimen,with higher safety and willingness to repeat examination.It can be recommended for bowel preparation for patients with constipation.

Objective To explore the preferences and needs of colorectal cancer patients for"Internet+TCM nursing services",aiming to provide a basis for the improvement of service quality and the formulation of relevant policies,so as to better meet the needs of patients.Methods A total of 189 patients with colorectal cancer who were admitted to a tertiary A Chinese Medicine hospital in Qingdao from September 2023 to July 2024 were selected as the research subjects.A general data questionnaire and Questionnaire on"Internet+Traditional Chinese Medicine Nursing Service"Preference of Colorectal Cancer Patients were used with 6 attributes,including average out-of-pocket cost,nurse qualification,service waiting time,service mode,comprehensiveness of service content,and platform service evaluation,each attribute with 2 to 3 levels.The preference,payment intention of"Internet+TCM nursing services"were analyzed by constructing a mixed Logit model,and the influencing factors of choice preference of different colorectal cancer patients was explored through subgroup analysis.Results Totally 189 questionnaires were sent out,and 156 valid questionnaires were collected,with an effective recovery rate of 82.54％.Among the respondents,112 patients(71.79％)actively accepted"Internet+TCM nursing services",and the attributes of"Internet+TCM nursing services"such as payment fee,service evaluation,service content and nurse qualification had an impact on nursing service preference of colorectal cancer patients(P＜0.05).Based on willingness to pay,the ranking of attributes was service evaluation,service content and nurse qualification.Factors such as education level and the presence of ostomy also affected the preference of"Internet+TCM nursing services"in patients with colorectal cancer(P＜0.05).Conclusion Patients with colorectal cancer prefer"Internet+TCM nursing services",which has an average service cost of 50 yuan per time,excellent platform service evaluation,comprehensive service content,specialized TCM nurses.The preferences and specific characteristics of patients with colorectal cancer can be considered to optimize the allocation of nursing resources and provide services in line with their preferences.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*