Objective To explore the efficacy and safety of pegylated doxorubicin liposome(PLD)in neoadjuvant chemotherapy(NAC)for breast cancer.Methods A total of 126 breast cancer patients treated with the NAC regimen containing PLD in the Third Xiangya Hospital of Central South University from Janu-ary 2018 to December 2022 were selected as the research subjects.The clinical efficacy,pathological efficacy and occurrence of adverse reactions of the patients were observed,and total pathological complete response(tpCR)rates of different molecular subtypes were analyzed.The changes in left ventricular ejection fraction(LVEF)were compared between before and after treatment.Results Among 126 patients,the clinical efficacy of NAC in 119 cases was evaluated,and the objective response rate(ORR)was 67.2％(80/119).A total of 123 patients were evaluated for the pathological efficacy,breast cancer pathological complete response(bpCR)rate was 13.8％(17/123);tpCR rate was 12.2％(15/123),in which the the human epidermal growth factor receptor 2(HER2)positive[hormone receptor(HR)negative]type had the highest rate(33.3％),followed by triple-negative(21.7％).There was no hand-foot syndrome occurred,and only one case developed the grade 2 oral mucositis.LVEF showed no statistically significant difference between before and after treatment[69.9％(51.0％,87.0％)vs.69.0％(57.0％,85.0％)](P＞0.05).Conclusion The NAC regimen containing PLD has a better effect on HER2—positive and triple-negative breast cancer.

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Objective To analyze the application effect of anterolateral femoral free flap transplantation based on three-dimensional reconstruction in CT angiography in the treatment of chronic osteomyelitis of the foot and ankle complicated with soft tissues defect.Methods A retrospective analysis was conducted on the clinical data of 105 patients with chronic osteomyelitis of the foot and ankle complicated with soft tissues defect who were admitted to Suining Central Hospital in Sichuan Province from January 2020 to January 2023.Patients enrolled were divided into the control group(n=52)and the observation group(n=53)according to different perforating blood vessel examination methods before surgery.The control group underwent anterolateral femoral free flap transplantation based on handheld Doppler ultrasound,while the observation group underwent anterolateral femoral free flap transplantation based on CTA three-dimensional reconstruction technology.Comparison between the groups was made on inflammatory factors(CRP,TNF-α and IL-6),skin flap repair effect,foot and ankle function(AOFAS)score,flap sensation,survival rate of skin flaps,and the incidence of adverse events.Results On day 14 after operation,serum CRP,TNF-α and IL-6 levels in the observation group were lower than those in the control group(P＜0.05).Six months after operation,the effect of flap repair in observation group was better than that in control group,and the survival rate of flap was higher than that in control group(100.00％vs 92.31％)(P＜0.05).Twelve months after operation,AOFAS score and flap sensation score of the observation group were higher(P＜0.05).The incidence of adverse events was lower in the observation group than in the control group(3.77％ vs.15.38％)(P＜0.05).Conclusion Anterolateral femoral free flap transplantation based on CTA 3D reconstruction technique can repair soft tissue defect and reduce the risk of adverse events while can cure chronic osteomyelitis.

Objective To investigate the effect of resveratrol(RES)on the function of osteoarthritis synovioblast(OA-FLS)and its molecular mechanism.Methods The purchased primary synovial cells were cultured to the third generation,and OA-FLS cell model was induced by IL-1β.The activity of FLS cells was observed by CCK-8 assay,and the appropriate RES intervention concentration was selected.The cells were divided into Control group,OA-FLS group,Low-RES group(1μmol/L)and High-RES group(5μmol/L).The effects of RES on the migration and invasion of OA-FLS were detected by cell scratch assay and Transwell assay.The effect of RES on OA-FLS apoptosis was detected by flow cytometry.The effects of RES on the expression of inflammatory factors in OA-FLS and re-lated proteins in NF-κB signaling pathway were detected by Western blot.Results The results of CCK-8 experiment showed that the concentration of RES above 10μmol/L significantly inhibited the viability of FLS cells,and the concentration of RES above 1 μmol/L and 5μmol/L had no significant effect on the viability of FLS cells.Compared with the Control group,the migration and invasion ability of OA-FLS group was enhanced,while the apoptosis ability was weakened,and the migration,invasion and apoptosis ability of OA-FLS group was significantly reversed after RES intervention.Western blot results showed that,compared with the Control group,the levels of inflammatory cytokines in OA-FLS group were increased,and the NF-κB signaling pathway was activated,while the treatment of OA-FLS with different concentrations of RES could reduce the expression of inflammatory cytokines and inhibit the transcription of nuclear fac-tors.Conclusion RES inhibited migration and invasion of OA-FLS,promoted apoptosis,and decreased the expression of inflammatory factors of OA-FLS,which may be related to the inhibition of NF-κB signaling pathway by RES.

Objective To explore the types of symptom clusters in patients with bladder instillation and identify the core symptoms through symptom network analysis,and to provide evidence for symptom management of the patients.Methods Convenience sampling was used to select 226 patients with bladder instillation for bladder cancer at a Tier-IIIA hospital in Guiyang from March 2023 to July 2024.Data were collected through review of medical record,general information questionnaires and symptom assessment questionnaires specific to the patients with bladder instillation.Exploratory factor analysis was used to extract symptom clusters,and symptom relationships were analysed using R language for network layout and centrality calculations.Results A total of 223 patients with bladder cancer completed the survey.Four symptom clusters were identified,namely the urinary system symptom cluster,digestive system symptom cluster,somatic symptom cluster and psychological symptom cluster,with a cumulative variance contribution rate of 66.038%.The symptom network analysis showed strong associations between dysuria and urethral pain during catheterisation,incomplete emptying and dysuria,as well as distress and poor sleep quality.In terms of centrality indicators,the top three symptoms by strength were dysuria(rS=2.26),incomplete emptying(rS=0.99)and poor sleep quality(rS=0.90).Of the expected impacts,the top three were dysuria(rE=2.09),poor sleep quality(rE=1.34)and frequency of urinary(rE=0.55).Regarding the closeness centrality,the top three were dysuria(rC=2.23),incomplete emptying(rC=0.64)and poor sleep quality(rC=0.54).Dysuria had the highest strength,expected impact and closeness centrality,indicating the dysuria was the core symptom in the patients with bladder cancer.Conclusion For the patients with bladder instillation experience,multiple and interconnected symptoms appear at the same time and together they form a symptom clusters,of which the pain in urination is the core symptom.Medical staff should consider symptom prevalence and core symptoms and to develop the targeted and precise management strategies for targeted nursing.

Objective To analyze the application effect of anterolateral femoral free flap transplantation based on three-dimensional reconstruction in CT angiography in the treatment of chronic osteomyelitis of the foot and ankle complicated with soft tissues defect.Methods A retrospective analysis was conducted on the clinical data of 105 patients with chronic osteomyelitis of the foot and ankle complicated with soft tissues defect who were admitted to Suining Central Hospital in Sichuan Province from January 2020 to January 2023.Patients enrolled were divided into the control group(n=52)and the observation group(n=53)according to different perforating blood vessel examination methods before surgery.The control group underwent anterolateral femoral free flap transplantation based on handheld Doppler ultrasound,while the observation group underwent anterolateral femoral free flap transplantation based on CTA three-dimensional reconstruction technology.Comparison between the groups was made on inflammatory factors(CRP,TNF-α and IL-6),skin flap repair effect,foot and ankle function(AOFAS)score,flap sensation,survival rate of skin flaps,and the incidence of adverse events.Results On day 14 after operation,serum CRP,TNF-α and IL-6 levels in the observation group were lower than those in the control group(P＜0.05).Six months after operation,the effect of flap repair in observation group was better than that in control group,and the survival rate of flap was higher than that in control group(100.00％vs 92.31％)(P＜0.05).Twelve months after operation,AOFAS score and flap sensation score of the observation group were higher(P＜0.05).The incidence of adverse events was lower in the observation group than in the control group(3.77％ vs.15.38％)(P＜0.05).Conclusion Anterolateral femoral free flap transplantation based on CTA 3D reconstruction technique can repair soft tissue defect and reduce the risk of adverse events while can cure chronic osteomyelitis.

Objective To investigate the effect of resveratrol(RES)on the function of osteoarthritis synovioblast(OA-FLS)and its molecular mechanism.Methods The purchased primary synovial cells were cultured to the third generation,and OA-FLS cell model was induced by IL-1β.The activity of FLS cells was observed by CCK-8 assay,and the appropriate RES intervention concentration was selected.The cells were divided into Control group,OA-FLS group,Low-RES group(1μmol/L)and High-RES group(5μmol/L).The effects of RES on the migration and invasion of OA-FLS were detected by cell scratch assay and Transwell assay.The effect of RES on OA-FLS apoptosis was detected by flow cytometry.The effects of RES on the expression of inflammatory factors in OA-FLS and re-lated proteins in NF-κB signaling pathway were detected by Western blot.Results The results of CCK-8 experiment showed that the concentration of RES above 10μmol/L significantly inhibited the viability of FLS cells,and the concentration of RES above 1 μmol/L and 5μmol/L had no significant effect on the viability of FLS cells.Compared with the Control group,the migration and invasion ability of OA-FLS group was enhanced,while the apoptosis ability was weakened,and the migration,invasion and apoptosis ability of OA-FLS group was significantly reversed after RES intervention.Western blot results showed that,compared with the Control group,the levels of inflammatory cytokines in OA-FLS group were increased,and the NF-κB signaling pathway was activated,while the treatment of OA-FLS with different concentrations of RES could reduce the expression of inflammatory cytokines and inhibit the transcription of nuclear fac-tors.Conclusion RES inhibited migration and invasion of OA-FLS,promoted apoptosis,and decreased the expression of inflammatory factors of OA-FLS,which may be related to the inhibition of NF-κB signaling pathway by RES.

Objective To explore the types of symptom clusters in patients with bladder instillation and identify the core symptoms through symptom network analysis,and to provide evidence for symptom management of the patients.Methods Convenience sampling was used to select 226 patients with bladder instillation for bladder cancer at a Tier-IIIA hospital in Guiyang from March 2023 to July 2024.Data were collected through review of medical record,general information questionnaires and symptom assessment questionnaires specific to the patients with bladder instillation.Exploratory factor analysis was used to extract symptom clusters,and symptom relationships were analysed using R language for network layout and centrality calculations.Results A total of 223 patients with bladder cancer completed the survey.Four symptom clusters were identified,namely the urinary system symptom cluster,digestive system symptom cluster,somatic symptom cluster and psychological symptom cluster,with a cumulative variance contribution rate of 66.038%.The symptom network analysis showed strong associations between dysuria and urethral pain during catheterisation,incomplete emptying and dysuria,as well as distress and poor sleep quality.In terms of centrality indicators,the top three symptoms by strength were dysuria(rS=2.26),incomplete emptying(rS=0.99)and poor sleep quality(rS=0.90).Of the expected impacts,the top three were dysuria(rE=2.09),poor sleep quality(rE=1.34)and frequency of urinary(rE=0.55).Regarding the closeness centrality,the top three were dysuria(rC=2.23),incomplete emptying(rC=0.64)and poor sleep quality(rC=0.54).Dysuria had the highest strength,expected impact and closeness centrality,indicating the dysuria was the core symptom in the patients with bladder cancer.Conclusion For the patients with bladder instillation experience,multiple and interconnected symptoms appear at the same time and together they form a symptom clusters,of which the pain in urination is the core symptom.Medical staff should consider symptom prevalence and core symptoms and to develop the targeted and precise management strategies for targeted nursing.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.