Objective To observe the effect of hypoxia(HX)on autophagy and pyroptosis-related protein expression of interleukin(IL)-1β-induced chondrocytes,and explore its mechanism of cartilage protection.Methods The expression of Bcl2/adenovirus E1B interacting protein 3-like(BNIP3L/NIX)in normal and osteoarthritis chondrocytes was analyzed by bioinformatics method.The primary chondrocytes from the knee joints of C57BL/6J neonatal mice were extracted and assigned to control group,IL-1β group,HX group,or IL-1β+HX group.The cells were treated with 10 ng/mL IL-1β for 24 h to simulate osteoarthritis-like chondrocyte injury,and HX treatment was by incubation with 1%O2 for 24 h.The expression levels of collagen typeⅡ α1(COL2α1),matrix metalloproteinase 13(MMP13),a disintegrin and metalloproteinase with thrombospondin 5(ADAMTS5),nucleotide-binding oligomerization domain-like receptor 3(NLRP3),gasdermin D N-terminal domain(GSDMD-N),apoptosis-associated speck-like protein containing a CARD(ASC),IL-18,hypoxia induced factor 1α(HIF1α),NIX,Beclin1,microtubule-associated protein-light chain 3(LC3),and p62 proteins were detected by Western blotting in each group.Results Bioinformatics analysis showed that the expression of NIX was lower in osteoarthritis chondrocytes than in normal chondrocytes.Western blotting showed that compared to the control group,the IL-1β group showed significant decreases in COL2α1 and NIX protein expression(both P＜0.05)and significant increases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and HIF1α protein expression(all P＜0.01).Compared to the IL-1β group,the IL-1β+HX group showed significant increases in COL2α1,HIF1α,NIX,Beclin1,and LC3 Ⅱ/LC3Ⅰ(all P＜0.01)and significant decreases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and p62(all P＜0.01).Compared to the control group,the HX group exhibited significant increases in HIF1α,NIX,Beclin1,and LC3Ⅱ/LC3Ⅰ(all P＜0.01)and decreases in p62,NLRP3,GSDMD-N and IL-18(all P＜0.05).Conclusion Hypoxia may eliminate NLRP3 inflammasome and inhibit chondrocyte pyroptosis through HIF1α/NIX-mediated mitochondrial autophagy,thereby reducing IL-1β-induced chondrocyte injury.

Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

Objective To explore the impact of irregular shape of head CT hematomas on postoperative re-bleeding and prognosis of patients with spontaneous intracerebral hemorrhage(ICH)who undergo craniotomy for hematoma evacuation.Methods We retrospectively enrolled consecutive patients with ICH who underwent craniotomy for hematoma evacuation in the Department of Neurosurgery of the Second People's Hospital of Guiyang Affiliated to Guizhou Medical University from January 2019 to June 2024.Baseline and clinical data were collected form the patients,including age,gender,smoking history,drinking history,hypertension,diabetes,history of anticoagulant use,admission systolic and diastolic blood pressure,admission National Institutes of Health stroke scale(NIHSS)score,Glasgow coma scale(GCS)score,time from onset to the first head CT,neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).Admission head CT scans were used to assess hematoma shape(regular or irregular),hematoma location(basal ganglia,lobar,multifocal),hematoma volume,perihematomal edema volume,the presence of midline shift,and intraventricular extension.Volume of the hematoma was assessed 2 days after surgery.Postoperative re-bleeding is defined as an increase in the volume of the hematoma by 12.5 ml compared to the previous postoperative CT scan within 2 weeks after surgery,or the reappearance of high-density areas in the focal area of the head CT scan during follow-up after complete hematoma clearance.Conduct patients follow-ups via telephone at 6 months postoperatively to assess their modified Rankin scale(mRS)scores.The sliding dichotomy method was applied to define prognosis based on the patients' baseline characteristics and disease severity.The prognostic score was calculated using formula:10 × admission GCS score-age-0.64 × admission hematoma volume.A prognostic score＞27.672 was considered potentially favorable,while a score ≤ 27.672 was considered potentially unfavorable.For patients with a potentially favorable prognosis,an mRS score of 0-2 was defined as a good outcome,and a score of 3-6 as a poor outcome.For those with a potentially unfavorable prognosis,an mRS score of 0-3 was defined as a good outcome,and a score of 4-6 as a poor outcome.In the comparison of baseline and clinical data between patients with regular and irregular hematoma shapes,factors with P＜0.05 were included in propensity score matching(PSM)to adjust for confounding variables.A 1∶1 matching was performed using the nearest neighbor method with a caliper value set to 0.25.Variables with statistically significant differences between groups after PSM matching were included in the multivariate Logistic regression analysis to identify influencing factors for postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy hematoma evacuation.The predictive value of irregular hematoma shape for postoperative rebleeding and poor prognosis in ICH patients was analyzed using receiver operating characteristic(ROC)curve analysis.Results(1)A total of 440 ICH patients were enrolled,including 342 males and 98 females,aged from 20 to 84 years with a mean age of(56±12)years.Statistically significant differences were observed in baseline and clinical data between patients with regular and irregular hematoma shapes before PSM,including age,admission GCS score,NIHSS score,NLR,proportion of patients with hematoma rupture into ventricles,preoperative hematoma volume,proportion of patients with midline shift,preoperative volume of hematoma surrounding edema,proportion of patients with hematoma located in multiple sites,and postoperative 2-day hematoma volume(all P＜0.05).After propensity score matching of these factors,298 ICH patients were included in the statistical analysis,comprising 228 males and 70 females,with an age range of 20 to 84 years and a mean age of(57±12)years.Following PSM,no statistically significant differences were observed in the baseline and clinical characteristics between patients with irregular and regular hematoma shapes(all P＞0.05).(2)After propensity score matching,28 patients experienced postoperative re-bleeding while 270 did not.Significant differences were observed between the two groups in the following factors:proportion of patients with a history of anticoagulant use,admission PLR,NLR,irregular hematoma shape,and hematoma volume at 2 days after operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using postoperative re-bleeding as the dependent variable and incorporating factors with P＜0.05 from the univariate analysis as independent variables,multivariate Logistic regression analysis identified irregular hematoma shape(OR,2.821,95％CI 1.142-6.968,P=0.025)and larger hematoma volume at 2 days post-operation(OR,1.062,95％CI 1.026-1.099,P＜0.01)as independent risk factors for re-bleeding following intracranial hematoma evacuation in ICH patients.ROC curve analysis demonstrated that irregular hematoma shape predicted postoperative re-bleeding with an area under the curve(AUC)of 0.62,showing a sensitivity of 71.4％and a specificity of 52.2％.(3)After propensity score matching,174 patients had poor prognosis while 124 had good prognosis.Significant intergroup differences were observed in age,admission GCS score,NIHSS score,irregular hematoma shape,proportion of patients with hematomas located in the basal ganglia and cerebral lobes,and hematoma volume at 2 days post-operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using poor prognosis as the dependent variable and incorporating factors with P＜0.05 from univariate analysis as independent variables,multivariate Logistic regression analysis revealed that advanced age(OR,1.039,95％CI 1.015-1.064,P=0.002),high admission NIHSS score(OR,1.068,95％CI 1.025-1.113,P=0.002),irregular hematoma shape(OR,2.675,95％CI 1.582-4.524,P＜0.01),and larger hematoma volume at 2 days post-operation(OR,1.033,95％CI 1.002-1.064,P=0.038)were independent risk factors for poor prognosis.Conversely,lobar hematoma location(OR,0.192,95％CI 0.073-0.504,P＜0.01)was identified as a protective factor.ROC curve analysis showed that irregular hematoma shape predicted poor prognosis after intracranial hematoma evacuation with an AUC of 0.61,demonstrating a sensitivity of 59.2％and specificity of 62.9％.Conclusion Irregular hematoma shape on head CT is an independent risk factor for both postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy for hematoma evacuation.

Mussel adhesive protein (MAP) is increasingly utilized in the biomedical field for the development of various bio-inspired products such as adhesives, protective films, and coatings with diverse properties, owing to its excellent biocompatibility, low immunogenicity, broad-spectrum adhesiveness, and biodegradability. The biological effects and mechanisms of MAP include adhesive film formation, cell migration and proliferation, anti-inflammatory and antioxidant activities, and inhibition of pigment formation. In dermatological applications, MAP demonstrates a significant potential in antibacterial and antipruritic effects, wound healing, barrier repair, and scar regeneration. In recent years, advances in understanding the secretion, distribution, and adhesion mechanisms of MAP, along with innovations in extraction methods, have led to the development of various natural MAP, recombinant MAP, mussel-inspired, and mussel-mimetic biomedical products. However, the biosafety, tissue compatibility, and functionality of these products remain subjects of debate. Further investigation is needed to elucidate the interactions between MAP-based products and various organ tissues and cells within complex biological systems, as well as to thoroughly evaluate their safety and efficacy. Such efforts are essential to achieve high-value utilization of MAP and to explore broader application prospects. Future research may focus on integrating MAP with emerging technologies such as nanotechnology and smart materials to further develop its multifunctional applications in the field of dermatology.

Objective To explore the impact of irregular shape of head CT hematomas on postoperative re-bleeding and prognosis of patients with spontaneous intracerebral hemorrhage(ICH)who undergo craniotomy for hematoma evacuation.Methods We retrospectively enrolled consecutive patients with ICH who underwent craniotomy for hematoma evacuation in the Department of Neurosurgery of the Second People's Hospital of Guiyang Affiliated to Guizhou Medical University from January 2019 to June 2024.Baseline and clinical data were collected form the patients,including age,gender,smoking history,drinking history,hypertension,diabetes,history of anticoagulant use,admission systolic and diastolic blood pressure,admission National Institutes of Health stroke scale(NIHSS)score,Glasgow coma scale(GCS)score,time from onset to the first head CT,neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).Admission head CT scans were used to assess hematoma shape(regular or irregular),hematoma location(basal ganglia,lobar,multifocal),hematoma volume,perihematomal edema volume,the presence of midline shift,and intraventricular extension.Volume of the hematoma was assessed 2 days after surgery.Postoperative re-bleeding is defined as an increase in the volume of the hematoma by 12.5 ml compared to the previous postoperative CT scan within 2 weeks after surgery,or the reappearance of high-density areas in the focal area of the head CT scan during follow-up after complete hematoma clearance.Conduct patients follow-ups via telephone at 6 months postoperatively to assess their modified Rankin scale(mRS)scores.The sliding dichotomy method was applied to define prognosis based on the patients' baseline characteristics and disease severity.The prognostic score was calculated using formula:10 × admission GCS score-age-0.64 × admission hematoma volume.A prognostic score＞27.672 was considered potentially favorable,while a score ≤ 27.672 was considered potentially unfavorable.For patients with a potentially favorable prognosis,an mRS score of 0-2 was defined as a good outcome,and a score of 3-6 as a poor outcome.For those with a potentially unfavorable prognosis,an mRS score of 0-3 was defined as a good outcome,and a score of 4-6 as a poor outcome.In the comparison of baseline and clinical data between patients with regular and irregular hematoma shapes,factors with P＜0.05 were included in propensity score matching(PSM)to adjust for confounding variables.A 1∶1 matching was performed using the nearest neighbor method with a caliper value set to 0.25.Variables with statistically significant differences between groups after PSM matching were included in the multivariate Logistic regression analysis to identify influencing factors for postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy hematoma evacuation.The predictive value of irregular hematoma shape for postoperative rebleeding and poor prognosis in ICH patients was analyzed using receiver operating characteristic(ROC)curve analysis.Results(1)A total of 440 ICH patients were enrolled,including 342 males and 98 females,aged from 20 to 84 years with a mean age of(56±12)years.Statistically significant differences were observed in baseline and clinical data between patients with regular and irregular hematoma shapes before PSM,including age,admission GCS score,NIHSS score,NLR,proportion of patients with hematoma rupture into ventricles,preoperative hematoma volume,proportion of patients with midline shift,preoperative volume of hematoma surrounding edema,proportion of patients with hematoma located in multiple sites,and postoperative 2-day hematoma volume(all P＜0.05).After propensity score matching of these factors,298 ICH patients were included in the statistical analysis,comprising 228 males and 70 females,with an age range of 20 to 84 years and a mean age of(57±12)years.Following PSM,no statistically significant differences were observed in the baseline and clinical characteristics between patients with irregular and regular hematoma shapes(all P＞0.05).(2)After propensity score matching,28 patients experienced postoperative re-bleeding while 270 did not.Significant differences were observed between the two groups in the following factors:proportion of patients with a history of anticoagulant use,admission PLR,NLR,irregular hematoma shape,and hematoma volume at 2 days after operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using postoperative re-bleeding as the dependent variable and incorporating factors with P＜0.05 from the univariate analysis as independent variables,multivariate Logistic regression analysis identified irregular hematoma shape(OR,2.821,95％CI 1.142-6.968,P=0.025)and larger hematoma volume at 2 days post-operation(OR,1.062,95％CI 1.026-1.099,P＜0.01)as independent risk factors for re-bleeding following intracranial hematoma evacuation in ICH patients.ROC curve analysis demonstrated that irregular hematoma shape predicted postoperative re-bleeding with an area under the curve(AUC)of 0.62,showing a sensitivity of 71.4％and a specificity of 52.2％.(3)After propensity score matching,174 patients had poor prognosis while 124 had good prognosis.Significant intergroup differences were observed in age,admission GCS score,NIHSS score,irregular hematoma shape,proportion of patients with hematomas located in the basal ganglia and cerebral lobes,and hematoma volume at 2 days post-operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using poor prognosis as the dependent variable and incorporating factors with P＜0.05 from univariate analysis as independent variables,multivariate Logistic regression analysis revealed that advanced age(OR,1.039,95％CI 1.015-1.064,P=0.002),high admission NIHSS score(OR,1.068,95％CI 1.025-1.113,P=0.002),irregular hematoma shape(OR,2.675,95％CI 1.582-4.524,P＜0.01),and larger hematoma volume at 2 days post-operation(OR,1.033,95％CI 1.002-1.064,P=0.038)were independent risk factors for poor prognosis.Conversely,lobar hematoma location(OR,0.192,95％CI 0.073-0.504,P＜0.01)was identified as a protective factor.ROC curve analysis showed that irregular hematoma shape predicted poor prognosis after intracranial hematoma evacuation with an AUC of 0.61,demonstrating a sensitivity of 59.2％and specificity of 62.9％.Conclusion Irregular hematoma shape on head CT is an independent risk factor for both postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy for hematoma evacuation.

Mussel adhesive protein (MAP) is increasingly utilized in the biomedical field for the development of various bio-inspired products such as adhesives, protective films, and coatings with diverse properties, owing to its excellent biocompatibility, low immunogenicity, broad-spectrum adhesiveness, and biodegradability. The biological effects and mechanisms of MAP include adhesive film formation, cell migration and proliferation, anti-inflammatory and antioxidant activities, and inhibition of pigment formation. In dermatological applications, MAP demonstrates a significant potential in antibacterial and antipruritic effects, wound healing, barrier repair, and scar regeneration. In recent years, advances in understanding the secretion, distribution, and adhesion mechanisms of MAP, along with innovations in extraction methods, have led to the development of various natural MAP, recombinant MAP, mussel-inspired, and mussel-mimetic biomedical products. However, the biosafety, tissue compatibility, and functionality of these products remain subjects of debate. Further investigation is needed to elucidate the interactions between MAP-based products and various organ tissues and cells within complex biological systems, as well as to thoroughly evaluate their safety and efficacy. Such efforts are essential to achieve high-value utilization of MAP and to explore broader application prospects. Future research may focus on integrating MAP with emerging technologies such as nanotechnology and smart materials to further develop its multifunctional applications in the field of dermatology.

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

【Objective】 To review the scientific research advances in the field of preschool children′s nutrition from 2012 to 2022, in order to provide reference for relevant policy formulation and further scientific exploration in this area. 【Methods】 High-quality literature published both domestically and internationally between 2012 and 2022 was retrieved through Web of Science (WOS) and China National Knowledge Infrastructure (CNKI) database. Excel and CiteSpace software were applied to visualize the research hotspots and frontier trends. 【Results】 A total of 1 816 English articles and 110 Chinese articles were included in the analysis. The cooperation network density of research institutions and authors was found to be low. Excluding the search terms, the top three English keywords were vitamin A (0.74), intervention (0.67), obesity prevention (0.55); the top three Chinese keywords were "anemia" (0.41), "obesity" (0.38), and "nutritional status" (0.18). In Chinese and English clusters, "anemia" and "physical activity" ranked first, respectively. The latest burst words identified were "dietary pattern" and "diet quality". 【Conclusions】 The number of English literature published in the field of preschool children′s nutrition is increasing, but it has shown a downward trend in the past three years in China. There are few studies in this field in China. The research hotspots primarily focus on the nutritional status of preschool children, with less attention paid to intervention research and methodological exploration. Further research in the field of preschool children′s nutrition in China may need to focus on the external determinants of preschool children′s nutrition, such as parental education, diet and food supply.

Pre-job training for new staff is vital in modern hospital management and talent team construction.This study conducted a survey with a questionnaire and interviews on the satisfaction and effectiveness of pre-job training for 274 new em-ployees of the Affiliated Brain Hospital of Guangzhou Medical University from 2020 to 2022.The results showed over 90％of the new employees were satisfied with course quality and organization and training organization,with the highest scores for hospital history and legal education and legal confidentiality education courses.Pre-job training significantly boosted employee enthusi-asm,organizational identity,and stress regulation capabilities.At the same time,there is room from optimization in aspects such as teaching methods,some course settings,and training schedule arrangements.