Tamoxifen(TAM)has been widely used for the treatment of ER+breast cancer.However,the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer.The tumor suppressor gene N-myc downstream-regulated gene 2(NDRG2)plays a significant role in the de-velopment of ER+breast cancer.However,it is unclear whether NDRG2 participates in mediating TAM resistance in ER+breast cancer.Here,we investigate the expression of NDRG2 mRNA and protein in TAM-sensitive and TAM-resistant ER+breast cancer cells.The results of immunoblotting experiments re-vealed a negative correlation between NDRG2 expression and TAM resistance ability in ER+breast cancer cells(P＜0.001).CCK-8 cell viability assays and soft agar colony formation assays showed that NDRG2 overexpression in TAM resistant cells significantly reduced the TAM IC50 value and the soft agar colony formation rate(P＜0.001).For the mechanism,the ERAD reporter protein assays showed that NDRG2 overexpression upregulated the expression of the ERAD reporter protein CD3ε-YFP and increased the lev-els of spliced XBP1s mRNA,leading to severe endoplasmic reticulum stress in TAM resistant cells(P＜0.001).Immunoblot analysis confirmed that overexpression of NDRG2 significantly increased the level of phosphorylation of the endoplasmic reticulum stress sensor IRE 1α and the expression levels of its down-stream protein factors,including ERdj4,P58IPK,EDEM and PDIA5(P＜0.001).The in vivo xenograft tumor experiments in mice further verified that NDRG2 overexpression significantly inhibited the growth of resistant tumors,which enhanced the therapeutic effect of TAM(P＜0.001).These findings indicate that increasing NDRG2 expression and triggering severe endoplasmic reticulum stress upon TAM treatment can reverse the resistance of ER+breast cancer cells to TAM and inhibits the growth of ER+breast canc-er tumors.Our results provide valuable new insights and potential targets for improving the clinical man-agement of TAM-resistance and prognosis in ER+breast cancer.

By analyzing the design principles and treatment modes of Gambro Prismaflex CRRT device,based on the basic structure and treatment process,and the typical failure cases of pressure joints and scale zeroing test failures in continuous renal replacement therapy(CRRT)equipment were analyzed,the targeted solution and maintenance strategies were proposed to ensure the stable and efficient operation of CRRT equipment.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Objective: To investigate the epidemiological characteristics of influenza in Yuhang District, Hangzhou City from 2019 to 2023, so as to provide the reference for formulating influenza prevention and control measures. Methods: Influenza case data with current address in Yuhang District was collected through the Chinese Disease Prevention and Control Information System from 2019 to 2023. Influenza-like illness data was collected through the Hangzhou Epidemiological Investigation System. Time distribution, population distribution and pathogen detection of influenza-like illness were descriptively analyzed. Results: There were 118 319 influenza cases reported in Yuhang District from 2019 to 2023, with an average annual reported incidence rate of 2 316.80/105. The highest incidence rate was seen in 2023, with a reported incidence rate of 5 736.82/105. The peak incidence of influenza occurred from November to March of the following year, presenting the winter and spring epidemic. The cases were mainly distributed in the age groups of 7 to 14 years and 25 to 59 years, with 31 310 and 34 470 cases, accounting for 26.46% and 29.13%, respectively. Influenza cases were reported in all 12 towns (streets) in Yuhang District, with the top two being Wuchang Street and Liangzhu Street, with the average annual incidence rates of 17 346.08/105 and 14 945.80/105, respectively. From 2019 to 2023, there were 103 868 cases of influenza-like illness, and 1 482 throat swab samples were collected. Among them, 260 positive samples of influenza virus were detected, with a positive rate of 17.54%. The peak detection period for positive specimens was from November to March of the following year, with 222 influenza virus positive specimens detected. The influenza virus types included H1N1, H3N2, and Victoria B, accounting for 25.77%, 38.85% and 35.38%, respectively. Conclusions The peak of influenza outbreak in Yuhang District from 2019 to 2023 was in winter and spring, with children and adolescents being the main affected objectives. H1N1, H3N2 and Victoria B were alternately prevalent. Prevention and control measures such as influenza vaccination should be strengthened.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Humans ; Plasma Cells/pathology* ; Hyperplasia/pathology* ; Immunoblastic Lymphadenopathy ; B-Lymphocytes/pathology* ; Lymphoma, T-Cell