ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective:To explore the correlation between ferroptosis-related proteins SLC7A11, GPX4, ACSL4 and the radiosensitivity and prognosis of nasopharyngeal carcinoma. And to investigate the potential of these proteins as molecular markers for predicting the radiosensitivity of nasopharyngeal carcinoma. Methods: A retrospective analysis was conducted on 52 cases of nasopharyngeal carcinoma （nasopharyngeal carcinoma group） and 20 cases of chronic nasopharyngiti s（control group）. The relevant clinical data were reviewed, and paraffin-embedded tissue blocks were collected for study. The expressions of SLC7A11, GPX4, and ACSL4 in pathological specimens were detected by immunohistochemical staining. The expression differences of ferroptosis-related proteins between the nasopharyngeal carcinoma group and the control group were analyzed. The nasopharyngeal carcinoma group was further divided based on the protein expression levels into high and low expression subgroups for SLC7A11, GPX4, and ACSL4. Subsequently, a differential analysis of clinical data and survival analysis was conducted for each of these subgroups. Finally, logistic regression analysis was performed to identify the factors influencing radiotherapy resistance in nasopharyngeal carcinoma. Results:①The differential analysis revealed that, compared to the control group, the nasopharyngeal carcinoma group exhibited significantly higher expression of SLC7A11 and GPX4, and lower expression of ACSL4 （P<0.05）. ②Notably, the proportion of patients displaying radioresistance was higher in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups （P<0.05）. However, the proportion of radioresistance in the ACSL4 high expression group was lower than that in the ACSL4 low expression group （P<0.05）. Survival analysis indicated that the 5-year overall survival rate was lower in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups（P<0.05）. However, the 5-year overall survival rate of the ACSL4 high expression group was higher than that of the ACSL4 low expression group（P<0.05）. ③logistic regression analysis showed that SLC7A11 and GPX4 was an independent risk factor for radioresistance in patients with nasopharyngeal carcinoma（P<0.05）. Conclusion:Nasopharyngeal carcinoma tissues over-express SLC7A11, GPX4, and under-express ACSL4. Over-expression of SLC7A11 and GPX4 are independent risk factors for radioresistance in patients with nasopharyngeal carcinoma. The inhibition of ferroptosis may be related to the occurrence, progression and radioresistance of nasopharyngeal carcinoma. Detection of the expression of SLC7A11, GPX4, and ACSL4 has guiding significance for the evaluation of radiosensitivity and prognosis of patients with nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/radiotherapy* ; Nasopharyngeal Neoplasms/pathology* ; Coenzyme A Ligases/metabolism* ; Radiation Tolerance ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Prognosis ; Long-Chain-Fatty-Acid-CoA Ligase ; Retrospective Studies ; Ferroptosis ; Male ; Female ; Middle Aged

Objective:To investigate the effects of long non coding RNA KCNQ1OT1(LncRNA KCNQ1OT1)on the migration and invasion of oral squamous cell carcinoma(OSCC)cells by regulating the microRNA-875-5p(miR-875-5p)/ETS like transcription factor 4(ELK4)axis.Methods:QRT-PCR was applied to detect the mRNA levels of LncRNA KCNQ1OT1,miR-875-5p,and ELK4 in OSCC cell lines(HSC-3,PE/CA-PJ15,HN13)and tissues.The dual luciferase assay was applied to detect the targeting relationship between LncRNA KCNQ1OT1 and miR-875-5p,and target relationship between miR-875-5p and ELK4.HSC-3 cells were used in control group,sh-NC group,sh-KCNQ1OT1 group,sh-KCNQ1OT1+anti-NC group,sh-KCNQ1OT1+anti-miR-875-5p group,miR-NC group,miR-875-5p mimic group,miR-875-5p mimic+pcDNA-NC group,and miR-875-5p mimic+ELK4 group.The migration and invasion abilities of HSC-3 cells were detected.Immunoblotting was applied to detect the protein expression of ELK4,MMP-2,MMP-9 and epithelial mesenchymal transition(EMT)(E-Cadherin,N-Cadherin,Vimentin).The nude mouse transplant tumor was applied to verify the effect of LncRNA KCNQ1OT1 on OSCC transplant tumors.Results:LncRNA KCNQ1OT1 and ELK4 mRNA expression increased in OSCC tissues and cancer cell lines,while miR-875-5p expression decreased(P＜0.05).Database predictions show that miR-875-5p specifically bound to LncRNAs KCNQ1OT1 and ELK4,respectively.Compared with the sh-NC group,the numbers of cell migration and cell invasion,the expression of LncRNA KCNQ1OT1,ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin in the sh-KC-NQ1OT1 group were lower,while the expression of miR-875-5p and E-Cadherin was higher(P＜0.05).Compared with the sh-KC-NQ1OT1+anti-NC group,the expression of miR-875-5p and E-Cadherin in the sh-KCNQ1OT1+anti-miR-875-5p group was lower,while the numbers of cell migration and cell invasion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin were higher(P＜0.05).Compared with the miR-NC group,the expression of miR-875-5p and E-Cadherin in the miR-875-5p mimic group was higher,while the numbers of cell migration and cell invasion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vim-entin were lower(P＜0.05).Compared with the miR-875-5p mimic+pcDNA-NC group,the numbers of cell migration and cell inva-sion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin in the miR-875-5p mimic+ELK4 group were higher,while the expression of E-Cadherin was lower(P＜0.05).The transplant tumor volume and weight of the sh-KCNQ1OT1 group were smaller than those of the sh-NC group,the mRNA and protein expression levels of LncRNA KCNQ1OT1,ELK4 were lower than those of the sh-NC group,and the expression level of miR-875-5p was higher than that of the sh-NC group(P＜0.05).Conclusion:Inhibition of LncRNA KCNQ1OT1 can target the miR-875-5p/ELK4 axis to inhibit migration,invasion,and EMT of OSCC cells.

Objective To explore the barriers to postoperative self-management behaviors in patients with pituitary adenoma and provide a theoretical basis for developing nursing intervention strategies.Methods Using a purposive sampling method,16 postoperative pituitary adenoma patients admitted to a tertiary hospital in Zhengzhou from July 2024 to January 2025 were selected for semi-structured interviews.The interview data were analyzed and refined through Colaizzi's phenomenological analysis method.Results A total of 4 themes and 12 subthemes were extracted,including postoperative physiological dysfunction(sensory dysfunction,difficulty in managing diabetes insipidus,fatigue syndrome),psychosocial adaptation barriers(self-image distress,fear of disease recurrence,restricted information delivery),challenges in maintaining health behaviors(environment-behavior conflicts,insufficient adherence to medication and activity guidelines,inadequate complication management),deficiencies in support systems(non-specific postoperative guidance,poor communication channels,insufficient coordination of medical resources).Conclusion Postoperative self-management behaviors in pituitary adenoma patients are influenced by multidimensional factors,necessitating comprehensive intervention strategies addressing physiological,psychological,behavioral,and systemic support levels.

Objective:To explore the clinical characteristics of patients with primary ureteral sarcomatoid carcinoma, thereby enhancing the understanding of the clinical context surrounding this disease.Methods:We report a case of primary ureteral sarcomatoid carcinoma in an elderly patient diagnosed through postoperative pathology at the Fourth Medical Center of the General Hospital of the People's Liberation Army.Additionally, a literature review was conducted to analyze articles related to primary ureteral sarcomatoid carcinoma published both domestically and internationally up to July 2024.This review summarizes and analyzes information regarding the clinical manifestations, diagnosis, treatment, and prognosis associated with this condition.Results:A total of 20 articles were reviewed, encompassing 24 cases of primary ureteral sarcomatoid carcinoma.Among the patients, 17 were older than 60 years, and when combined with the cases presented in this review, a total of 18 cases involved patients over the age of 60.Of these, 66.7%(12/18)were male, with a median age at diagnosis of 65 years.The reported cases often exhibited no clinical manifestations in the early stages; however, as the disease progressed, common urinary symptoms emerged, including frequency, urgency, pain, or painless hematuria, occurring throughout the ureteral course.The lesions were predominantly located in the left ureter(17 cases), which frequently exhibited dilation with effusion.Pathologic examination revealed the presence of microscopic spindle cells.Surgical treatment was administered to 20 patients, of whom 9 did not experience recurrence or metastasis during the follow-up period, while 7 cases resulted in mortality.Conclusions:Primary ureteral sarcomatoid carcinoma is a rare malignant tumor of the ureter.Its clinical manifestations are generally regarded as non-specific, making pathological examination the gold standard for diagnosis.Immunohistochemical and imaging studies can assist in the diagnostic process.The current preferred treatment modality is surgical resection, while first-line therapies that combine chemotherapy with immunotherapy and targeted therapy have been shown to enhance tumor control.

Objective To explore the application effect of personalized osteotomy guide plate in high tibial osteotomy for patients with knee osteoarthritis(KOA).Methods A total of 99 patients with KOA who underwent open wedge high tibial osteotomy(OWHTO)in our hospital from January 2022 to January 2023 were selected and randomly divided into a study group(50 cases)and a control group(49 cases)using a random number table method.The control group received traditional medial OWHTO treatment,and the study group received a combination of medial OWHTO and personalized osteotomy guide plate treatment.The indexes of operation and postoperative rehabilitation,serum inflammatory stress factor[C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),cortisol(Cor),adrenocorticotropin(ACTH)],anatomical structure of knee joint[tibial plateau posterior Angle(PTSA),proximal medial tibial Angle(MPT A),hip knee ankle Angle(HKA)],knee function,ACL shape and function,postoperative complications were compared between the two groups.Results The amount of bleeding,the number of intraoperative fluoroscopy,and the postoperative drainage volume in the study group were(138.69±24.03)ml,(4.83±1.07)times,and(228.95±38.72)ml,respectively,which were all less than those in the control group(154.28±27.16)ml,(7.15±1.14)times,and(271.61±42.19)ml.In the study group,the operation time,incision length,and hospitalization time were(40.96±7.28)min,(8.96±0.85)cm,and(10.73±2.05)d,respectively,which were all shorter than those in the control group[(52.31±10.12)min,(9.51±1.03)cm,and(12.16±2.37)d],with statistically significant differences(P＜0.05).The levels of serum CRP,TNF-α,Cor,and ACTH in the study group on the 3rd day after the operation were(31.36±4.68)mg/L,(26.71±3.84)ng/ml,(241.28±27.45)ng/ml,and(18.65±3.01)pmol/L,respectively,which were lower than those in the control group[(35.07±5.16)mg/L,(30.29±4.15)ng/ml,(279.65±30.12)ng/ml,and(21.73±3.28)pmol/L,respectively],and the differences were statistically significant(P＜0.05).The Hospital for Special Surgery(HSS)knee score and Knee Society Score(KSS)of the study group at 12 months after surgery were(81.24±6.85)points and(78.26±6.14)points,respectively,which were higher than those of the control group[(78.08±6.42)points and(75.53±5.82)points,respectively],with statistically significant differences(P＜0.05);at the 12th month after surgery,the width of the ACL body in the study group was(5.68±0.71)mm,which was greater than that in the control group[(5.12±0.64)mm].The amount of anterior tibial displacement was(5.81±0.43)mm,which was smaller than that in the control group(6.19±0.41)mm,and the differences were statistically significant(P＜0.05);the incidence of postoperative complications in the study group was 4.00％,which was lower than that in the control group(18.37％),and the difference was statistically significant(P＜0.05).Conclusion The combined treatment of medial OWHTO and personalized osteotomy guide plate can reduce surgical trauma in patients with KOA,lower the incidence of complications,facilitate patient recovery,while maintaining the morphology and function of the ACL,and improving prognosis.

Objective:To analyze the clinical features of pachydermoperiostosis (PDP) and improve its diagnostic level.Methods:A retrospective analysis was conducted on the clinical data of four patients with PDP treated at Sun Yat-sen Memorial Hospital, Sun Yat-sen University from 2015 to 2023, including clinical manifestations, laboratory tests, imaging examinations, and genetic testing results.Results:All four patients were male with an average onset age of 15 years old (ranging from 9 to 18 years old). One patient′s uncle had PDP, and another patient′s parents were consanguineous, though neither parent showed signs of PDP. All four patients exhibited clubbing, skin thickening, and acne; three had frontal bossing and deepened nasolabial folds; two showed scalp sulci changes on head MRI, and all had periosteal thickening of the phalanges visible on X-ray. One patient accompanied with hypokalemic nephropathy, and another had gastric ulcer. One patient underwent whole exome sequencing test which revealed a homozygous mutation, SLCO2A1 gene c.1406C>T, leading to a protein change p.Pro469Leu. Computational tools REVEL, SIFT, and Polyphen2 predicted this variant as deleterious.Conclusion:In addition to skin thickening, frontal bossing, scalp sulci changes, clubbing, and periosteal proliferation, patients with PDP may also present with hypokalemic nephropathy and gastric ulcer. The SLCO2A1 gene c.1406C>T mutation may be pathogenic.