Objective To analyze the factors affecting pathological complete response (pCR) of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy, and construct a nomogram to forecast the pCR rate. Methods The clinical and pathological data of 348 TNBC patients who received neoadjuvant chemotherapy in the Air Force Medical University-Affiliated Xijing Hospital from May 2018 to May 2021 were collected and set as modeling set. The clinical and pathological data of 69 TNBC patients who received neoadjuvant chemotherapy in the Xi'an No.3 Hospital from May 2018 to May 2021 were collected and set as validation set. The clinical and pathological characteristics were compared between the modeling set and the validation set. In the modeling set, the independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy were screened by LASSO regression model analysis, and the nomogram model was constructed. Internal validation of the model was conducted using Bootstrap method, and the discrimination of the model was assessed by receiver operating characteristic (ROC) curve. The accuracy of the model was evaluated by the calibration curve and the clinical benefits and application value of the model were evaluated by clinical decision curve analysis (DCA). Results There were significant differences in surgical method and T stage between the patients in modeling set and validation set (P<0.05). The results of analysis of LASSO regression model showed that T stage, N stage, the use of platinum drugs and clinical efficacy evaluation were independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy (P<0.05). Based on the above variables, the nomogram models were constructed. In modeling set, area under curve (AUC) was 0.811 (95%CI 0.763-0.859); in validation set, AUC was 0.801 (95%CI 0.727-0.928). The Bootstrap method showed the C-index for internal validation was 0.79, indicating the model has good discrimination in both the modeling and validation sets. The calibration curve analysis showed that model predicted pCR rates had a good consistency with the actual observed values, and the DCA showed that model can bring clinical benefit. Conclusion The nomogram can accurately predict the pCR rates of TNBC patients after neoadjuvant chemotherapy and provide scientific basis for clinical diagnosis and treatment.

Objective To investigate the role of necroptosis key genes in spinal cord injury using bioinformatics methods to provide new targets for the diagnosis and treatment of spinal cord injury. Methods The peripheral blood transcriptome data of spinal cord injury samples (n=38) and healthy control samples (n=10) were obtained from GSE151371 data set in Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes and perform functional enrichment analysis. Machine learning algorithms (random forest and LASSO) and protein-protein interaction (PPI) networks are used to screen for necroptosis key genes and construct a diagnostic nomogram for spinal cord injury. Establish a rat spinal cord injury model to further verify the expression of necroptosis key genes by Western blotting and immunofluorescence staining. Results A total of 2050 differentially expressed genes were identified in the two groups. KEGG pathway enrichment analysis showed that the differentially expressed genes were involved in the nucleotide-binding oligomerization domain (NOD)‑like receptor signaling pathway, hematopoietic cell lineage, and necroptosis; GO enrichment analysis showed that the differentially expressed genes were involved in the activation of leukocytes, tertiary granulation, and regulation of the defense response, and so on. Intersection analysis screened 15 necroptosis differentially expressed genes. KEGG pathway enrichment analysis showed that necroptosis differentially expressed genes were involved in necroptosis, influenza, and NOD-like receptor signaling pathways; GO enrichment analysis showed that necroptosis differentially expressed genes were significantly enriched in the cellular response to cytokine stimulation, cytokine-mediated signaling pathways, and response to cytokines. Integration of two machine learning algorithms and PPI analysis further screened two necroptosis key genes (IL1B and PLA2G4A). The nomogram established using IL1B and PLA2G4A can be used for early prediction of the occurrence of spinal cord injury. The validation results of the rat spinal cord injury model showed that the protein expression of IL-1β and PLA2G4A in the spinal cord injury group were significantly higher than those in the sham group (P<0.05). Conclusions IL1B and PLA2G4A as key genes of necroptosis involved in the development of spinal cord injury, can be used to predict the development of spinal cord injury with the promise of being new targets for the prevention and treatment of spinal cord injury

Objective Based on data from the US SEER database, this study investigates the incidence, epidemiological characteristics, treatment modalities, prognosis assessment, and risk stratification of advanced-stage lung adenocarcinoma in young patients. Methods SEER*Stat software was used to collect the incidence rates of lung adenocarcinoma among people under 50 in the US from 2000 to 2020, with annual percentage changes (APCs) calculated using Joinpoint software. Clinical data of 4490 advanced-stage lung adenocarcinoma patients under 50 years old from the SEER database (2010-2018) were retrospectively collected and analyzed. Kaplan-Meier method was used to calculate overall survival, log-rank test to estimate survival rates, and Cox proportional hazards regression model to conduct univariate and multivariate prognostic analyses, and a nomogram model was established to predict the survival of young advanced lung adenocarcinoma patients. The predictive performance of the nomogram was evaluated using ROC curves and calibration curves. X-Tile software was used for risk stratification of the prognosis of young advanced lung adenocarcinoma patients. Results From 2000 to 2020, the incidence rates of young lung adenocarcinoma in men and women in the US decreased from 2.1/100 000 and 2.2/100 000 to 1.1/100 000 and 1.5/100 000 respectively, with APCs of -2.16 and -1.39 (P<0.05). Compared to patients aged 40 to <50 years, patients under 40 were more likely to develop bone metastasis, liver metastasis, and lung metastasis, had a higher probability of receiving chemotherapy, tumors were more likely to occur in the lower or middle lobes of the lung, but had a lower probability of receiving radiotherapy, with statistically significant differences (P<0.05). Cox regression analysis showed that gender, age, race, N stage, M stage, subsite, liver metastasis, and bone metastasis were prognostic factors for young advanced lung adenocarcinoma patients (P<0.05); male patients had worse prognosis than female patients (HR=1.17, 95%CI 1.09-1.25); African American patients had worse prognosis than Caucasian patients (HR=1.12, 95%CI 1.02-1.23), other races had better prognosis than Caucasian patients (HR=0.83, 95%CI 0.77-0.97); patients aged 40 to <50 had worse prognosis than those under 40 (HR=1.34, 95%CI 1.21-1.48); patients with bone metastasis (HR=1.29, 95%CI 1.19-1.40) and liver metastasis (HR=1.40, 95%CI 1.28-1.54) had worse prognosis, with statistically significant differences (P<0.05). Based on the above prognostic factors, a nomogram model was established to predict 1-year, 3-year, and 5-year survival with areas under the curve (AUC) of 0.717, 0.692, and 0.699 respectively, and the calibration curve was close to the 45° diagonal. According to the risk scores, patients were divided into low-risk group [1017 cases (22.7%)], medium-risk group [2871 cases (63.9%)], and high-risk group [602 cases (13.4%)]. The difference is statistically significant comparing the survival rates among three groups (P<0.0001). Conclusion Gender, age, race, N stage, M stage, subsite, liver metastasis, and bone metastasis are prognostic factors for young advanced lung adenocarcinoma patients, and the nomogram model established based on these factors has high predictive performance.

Objective To investigate how flavokawain B (FKB) affects the proliferation and migration of triple-negative breast cancer (TNBC) cells by downregulating the androgen receptor (AR). Methods The expression of AR in breast cancer and normal tissues was analyzed using the GEPIA2 database. Expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and AR was detected in six breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, Hs-578T, and MDB-MA-231) by Western blotting. The effect of FKB (0, 10, 20, 30, 40, 50, 60 μmoL/L) treatment of 24, 48, and 72 h on the proliferative activity of SUM159PT breast cancer cells was assessed using the CCK-8 assay under normal or androgen deprivation conditions. The mRNA and protein of AR expression was measured by qRT-PCR and Western blotting after 30 μmoL/L FKB treatment of SUM159PT cells for 0, 4 and 8 h. SUM159PT cells were set as control group (treatment with 0.1% DMSO), dihydrotestosterone (DHT) group (treatment with 10 nmol/L DHT), FKB group (treatment with 15 μmol/L FKB), DHT+FKB group (treatment with 10 nmol/L DHT and 15 μmol/L FKB), AR antagonist enzalutamide (ENZA) group (treatment with 40 μmol/L ENZA), and DHT+ENZA group (treatment with 10 nmol/L DHT and 40 μmol/L ENZA) under androgen deprivation conditions. Cell proliferation, migration, and colony formation abilities in the above groups were determined using the CCK-8 method, Transwell assay, and clone formation test. Western blotting was also used to detect the expression levels of EMT-related proteins (N-cadherin, Occludin, Vimentin) and AR protein. Results AR mRNA expression level was significantly higher in breast cancer tissue than in normal breast tissue (P<0.05). AR was expressed at comparable levels in five different breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, and Hs-578T) in addition to MDB-MA-231. FKB can downregulate AR mRNA and protein levels (P<0.05). Western blotting results showed that DHT could upregulate AR protein levels in SUM159PT cells, but FKB could prevent the DHT-induced upregulation of AR protein levels (P<0.05). FKB and ENZA decreased SUM159PT cell proliferation and migration and DHT-mediated cell proliferation and migration (P<0.05). FKB and ENZA can reduce N-cadherin and Vimentin protein levels and counteract DHT-induced increases in N-cadherin and Vimentin protein levels (P<0.05). In addition, FKB may increase Occludin expression and counteract the DHT-induced decrease in Occludin protein expression (P<0.05). Conclusion Flavokawain B could inhibit the proliferation, migration, and clonogenic ability of TNBC cells by regulating AR expression.

Chronic kidney disease (CKD) commonly used dietary assessments including 24-hour dietary recall (24 h DR)/3-day dietary recall (3DDR), food frequency questionnaire (FFQ), dietary records, and estimation of dietary protein intake based on nitrogen balance. Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method, it is crucial to develop an FFQ suitable for Chinese CKD patients. This review summarizes the advantages and disadvantages of dietary assessment methods for CKD, the current research status, and the content and steps involved in establishing an FFQ, with the aim of providing reference for the modification of FFQ for Chinese CKD patients.

Objective To explore the influence factors and predictors of treatment response after adrenocorticotropic hormone (ACTH) in infantile epileptic spasms syndrome(IESS). Methods A retrospective analysis was conducted on 80 cases of IESS infants(50 males and 30 females) who were diagnosed and treated with ACTH in Chengdu Women's and Children's Central Hospital from January 2016 to December 2020. Patients were divided into effective group (n=39) and ineffective group (n=41) based on their response of ACTH treatment after 28 days, and their clinical data including the patients' basic information, etiology, treatment programmer, per- and post-treatment Kramer scores of electroencephalogram (EEG) hypsarrhythmia severity and so on, were collected to compare and analyze between the two groups. A modified Poisson regression model was constructed to discover predictors of outcome, and the receiver operating characteristic (ROC) curves were used to assess the prognosis evaluation of the positive predictive value. Results The ages at seizure onset ranged from one month and seven days to one year and nine months. Seizure types included simple epileptic spasms in 66 cases and combined with other types(focal and secondarily generalized seizures) in 14 cases. Thirty-two cases had been given anti-seizure medications (ASMs) before ACTH treatment. The median Kramer scores per-treatment and at 14 days post-treatment were 10.0 (8.3, 12.0) and 6.0 (4.0, 7.0), respectively. After ACTH treatment, 39(48.8%) cases were effective. Compared with the effective group, the ineffective group had significantly higher proportion of abnormal perinatal conditions, unknown aetiology with normal development, ASMs given before ACTH treatment, the dosages of ACTH greater than 2 U/(kg·d), combinations of two or more ASMs, poor control, and still seizure attack after ACTH treatment of 14 days (P<0.05). Additionally, the Kramer scores after ACTH treatment of 14 days in the ineffective group were also significantly higher (P<0.05). The modified Poisson regression model showed that there were significant statistic differences between the two groups on ASMs given before ACTH treatment (RR=0.546, 95%CI 0.357-0.833, P=0.005) and Kramer scores of hypsarrhythmia severity (RR=0.701, 95%CI 0.620-0.792, P<0.001),while there were no significant differences between the two groups in term of ages, gender, perinatal conditions, etiologies, seizure types, Kramer scores before treatment, time lag between onset and treatment, duration of ACTH treatment, kinds of ASMs combination. ROC curve analysis showed that only Kramer scores at 14 days after ACTH treatment could predict the treatment response with sensitivity and specificity of 92.7% and 84.6%, respectively, with Youden index of 0.773. The area under the ROC curve was 0.930 (95%CI 0.873-0.987, P<0.001) and the cut-point of the score was 6, indicating that the higher the Kramer scores at 14 days after ACTH treatment, the worse the treatment response. The treatment response rate would reduce by about 30.0% if the Kramer score increased by one point. Conclusion ASMs given before ACTH treatment may influence the treatment response. Kramer scores greater than 6 at day 14 after ACTH treatment may be used as a predictor of treatment response after ACTH in IESS patients.

Linezolid, a fully synthetic oxazolidinone antibiotic, is mainly used to treat severe infections caused by Gram-positive drug-resistant bacteria. In recent years, with the rise in drug-resistant bacteria, the clinical utilization rate of linezolid and the incidence of linezolid-related adverse reactions in the hematological system and metabolic system have increased. The main adverse reactions include thrombocytopenia, anemia and lactic acidosis. Studies have shown that the causes of adverse reactions in linezolid-induced hematological system and metabolic system are diverse, and the mechanisms are not fully elucidated. In this review, the pharmacokinetic characteristics, mechanism of adverse reactions, risk factors, as well as preventive measures and individualized drug administration strategies of linezolid in vivo were discussed based on literature reports at home and abroad, aiming to provide references for clinical prevention and treatment of linezolid-related adverse reactions of hematological system and metabolic system.

Objective To investigate the role and underlying mechanisms of WD repeat domain 82 (WDR82) protein in the pathogenesis and progression of glioma. Methods We analyzed the expression level of WDR82 in glioma tissues using GEPIA and UALCAN databases and further assessed WDR82 protein expression in glioma and adjacent normal tissues through immunohistochemical staining. The correlation between WDR82 expression and the prognosis of glioma patient was evaluated using Kaplan-Meier plotter. Experiments were conducted on A172 and U251 cell lines, which were categorized into four groups: control group (transfected with 3 μg pcDNA3), shR-control group (transfected with 3 μg pSilencer 2.1-U6), pWDR82 group (transfected with 3 μg pWDR82), and shR-WDR82 group (transfected with 3 μg shR-WDR82). Post-transfection, we confirmed transfection efficiency at 48 hours using qRT-PCR and measured cell viability at the same time point with CCK-8 assay. Clone formation assay was employed to assess cell proliferation capacity after 14 days of transfection, while flow cytometry was utilized to analyze cell apoptosis after 48 hours of transfection. Additionally, Western blotting was conducted to determine the expression levels of proteins related to proliferation and Akt/mTOR signaling pathway after 48 hours of transfection. Finally, the effect of WDR82 on tumor growth in NOD-SCID mice was investigated using tumor carrying experiment in vivo. Results Analysis of WDR82 expression in glioma tissues using GEPIA and UALCAN databases, along with immunohistochemical staining, revealed significantly higher expression levels compared to normal and paracancerous tissues (P<0.05). Additionally, WDR82 expression was not associated with gender or age of patients (P>0.05). Kaplan-Meier plotter analysis indicated that elevated WDR82 expression correlated with a poor prognosis in glioma patients (log-rank P=0.029). Overexpression of WDR82 notably enhanced the proliferation and inhibited the apoptosis of A172 and U251 cells, and also significantly upregulated the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR in A172 and U251 cells (P<0.05). Conversely, WDR82 knockdown had the opposite effects, inhibiting cell proliferation, increasing apoptosis and downregulating the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR (P<0.05). WDR82 knockdown in U251 cells significantly inhibited tumor growth in NOD-SCID mice (P<0.05). Conclusion High expression of WDR82 promotes the proliferation of glioma cells and the growth of tumors in vivo by regulating the AKT/mTOR signaling pathway.

Objective To investigate the effects of Chaihuang Yishen Granules on renal fibrosis in unilateral ureteral obstruction (UUO) mice and its underlying mechanisms. Methods Twenty-four 8-week-old male C57BL/6 mice were randomly divided into control group, model group, and low and high dose groups of Chaihuang Yishen Granules (6 in each group). In control group, only right kidney ureter was exposed and dissected. In model group, the UUO animal model was established by UUO. In low and high dose groups, mice were administered intragastrically at doses of 3.8 and 7.6 g/kg of Chaihuang Yishen Granules respectively,following the model group's method to establish the UUO model. After 7 days, the mice were euthanized and renal samples were collected. HE and Masson staining were used to observe pathological changes and fibrosis degree of the kidneys in each group, Sirius red staining was used to observe collagen deposition. The expression levels of α-smooth muscle actin (α-SMA), fibronectin (FN), type Ⅰ collagen (Col-Ⅰ), glycogen synthase kinase 3β (GSK-3β), and β-catenin related proteins were detected using Western blotting. Changes in A33 and GSK-3β, β-catenin mRNA levels were measured by RT-PCR. Additionally, a normal transformed C3H mouse kidney-1 (TCMK1) was used as control (normal group); an in vitro fibrosis model was established using TCMK1 stimulated with Transforming Growth Factor‑β (TGF‑β); and an in vitro drug model was established using TCMK1 treated with serum containing Chaihuang Yishen Granules. A33 was overexpressed in TCMK1 cells using a transfection with an A33 overexpression plasmid, and changes in fibrosis-related indicators and the expression of A33 and GSK-3β, β-catenin mRNA were observed. Results RT-PCR results showed that, compared with control group, A33 level was significantly increased in model group, while it was significantly reduced in both low and high dose groups of Chaihuang Yishen Granules (P<0.05). Western blotting showed that the expression levels of fibrosis-related factors such as α-SMA, FN, Col-Ⅰ in model group were significantly higher than those in control group (P<0.05); while compared with model group, the expression levels of α-SMA, FN, Col-Ⅰ in low and high dose groups of Chaihuang Yishen Granules were significantly lower (P<0.05). HE, Masson, immunohistochemical staining results showed that model group had severe kidney structural damage, significant increase in collagen deposition, and significantly higher expression levels of GSK-3β and β-catenin proteins compared with those in control group (P<0.01). In contrast, low and high dose groups of Chaihuang Yishen Granules had good kidney structure, significant improvement in kidney damage and fibrosis, and significantly lower expression levels of GSK-3β and β-catenin proteins compared with those in model group (P<0.05). In vitro experiment results confirmed that, compared with normal group, A33 overexpression promoted the upregulation of fibrosis-related factors in TCMK1 cells, significantly increase the expression of downstream target genes GSK-3β and β-catenin mRNA in the Wnt/β-catenin signaling pathway (P<0.05), and A33 overexpression reversed the cellular fibrosis changes downregulated by the serum containing Chaihuang Yishen Granules (P<0.01). Conclusion Chaihuang Yishen Granules significantly improve renal fibrosis in UUO mice by downregulating the A33/Wnt/β-catenin signaling pathway, suggesting that A33 may be a potential therapeutic target for renal fibrosis.

Objective To explore the effects of standardized environmental enrichment (EE) on cognitive function and serum brain-derived neurotrophic factor (BDNF) levels in patients with post-stroke dementia. Methods A prospective study was conducted, including 80 patients with post-stroke dementia admitted to Department of Traditional Chinese Medicine Rehabilitation, 910th Hospital of the Joint Logistics Support Force of Chinese PLA from January 2021 to May 2023. Patients were randomly divided into control group, cognitive training (COG) group, aerobic exercise training (AE) group and environmental enrichment (EE) group, with 20 cases in each group. All patients received routine treatment, with COG group receiving additional cognitive function training (30 minutes each time), AE group receiving additional aerobic exercise training (30 minutes each time), and EE group receiving both aerobic exercise and cognitive function training (15 minutes of aerobic exercise training and 15 minutes of cognitive training each time). The training was conducted once a day, 5 days a week, for a total of 8 weeks. The patients' mini-mental state scale (MMSE), modified Barthel index (MBI), Hamilton depression scale (HAMD), stroke-specific quality of life (SS-QOL) score and serum levels of BDNF were assessed before treatment, at 4 weeks and 8 weeks of treatment, respectively. Results Before treatment, there were no significant differences in general information, MMSE, MBI, HAMD, SS-QOL scores, and serum levels of BDNF among the four groups (P>0.05). After 4 and 8 weeks of treatment, the above indicators of the four groups were improved compared with those before treatment, with all differences being statistically significant (P<0.05). Inter-group comparison showed that after 4 and 8 weeks of treatment, MMSE, MBI, SS-QOL scores, and serum BDNF levels in COG, AE and EE groups were significantly higher than those in control group, and HAMD scores were significantly lower than those in control group (P<0.05). In addition, MMSE, MBI, SS-QOL scores and BDNF levels of group EE were better than those of other 3 groups, while HAMD scores were lower than those of other 3 groups, with all differences being statistically significant (P<0.05). There was no significant difference in above outcome indicators between COG group and AE group after 4 and 8 weeks of treatment (P>0.05). Conclusion Standardized enrichment environment can significantly enhance cognitive function, daily living abilities of post-stroke dementia patients, alleviate depression symptoms, and improve the quality of life, which may be related to the increase in serum BDNF levels.