OBJECTIVE: To explore the significance of the plasma cell percentage and immature plasma cells in the prognosis of patients with multiple myeloma (MM). METHODS: The clinical data of 126 newly diagnosed MM patients in Gansu Provincial Hospital from June 2017 to November 2022 were retrospectively analyzed. The enrolled patients were divided into a higher plasma cell percentage group (group A) and a lower plasma cell percentage group (group B) according to the median plasma cell percentage (33.5%). The clinicopathological data of the two groups were compared, and the effect of plasma cell percentage on the prognosis of MM patients was analyzed using survival curves. On this basis, group A and group B were divided into subgroups with immature plasma cells (A1 group, B1 group) and subgroups without immature plasma cells (A2 group, B2 group), respectively, then the survival curves were used to analyze the effect of immature plasma cells on the prognosis of MM patients. RESULTS: Among the 126 patients with MM, the proportions of patients with ISS stage III, elevated β₂-microglobulin(β₂-MG) level, and immature plasma cells in Group A were significantly higher compared those in Group B ( P =0.015, P =0.028, P =0.010). The median overall survival(OS) and progression-free survival(PFS) of group A were 32 months and 10 months, respectively. The median OS of group B was not reached, and the median PFS was 32 months. The 3-year OS rates of patients in group A and group B were 46.7% and 62.2%, respectively ( P =0.021), and the 3-year PFS were 29.2% and 42.5%, respectively ( P =0.033). There were no significant differences in OS and PFS between group A1 and group A2, or between group B1 and group B2 ( P >0.05). Multivariate COX survival analysis showed that the plasma cell percentage ≥33.5%（HR=1.253, 95%CI : 0.580-2.889, P =0.018）, age ≥65 years (HR=2.206, 95%CI : 1.170-3.510, P =0.012), lactate dehydrogenase(LDH) ≥250 U/L (HR=1.180, 95%CI : 0.621-2.398, P =0.048) and β₂-MG ≥3.5 mg/L (HR=1.507, 95%CI : 0.823-3.657, P =0.036) were independent risk factors affecting OS in MM patients. CONCLUSION MM patients with a higher plasma cell percentage (≥33.5%) at the initial diagnosis have a later disease stage, poorer OS and PFS, compared to the patients with a lower percentage(<33.5%) of plasma cells. The presence or absence of immature plasma cells has no significant impact on the survival of MM patients.
Humans ; Multiple Myeloma/pathology* ; Prognosis ; Plasma Cells/cytology* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Bone Marrow

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Radiomics is a rapidly developing field,which can transform the black and white gray-scale information of traditional CT,MR1,positron emission tomography(PET),and other images into quantitative radiomics features,obtain rich deep features of lesions,and provide more valuable information for clinical diag-nosis and treatment.Radiomics capture these time-varying lesion characteristics in continuous imaging,and then discover markers and patterns of disease evolution,progression and treatment response,which are used to solve clinical problems.Image data are mineable,and in large enough data sets,they can be used to complete advancements from the individual level to the molecular/digital level.Although the development of radiomics is still in its infancy,there have been many studies on its application in nasopharyngeal carcinoma.This article reviews the application of radiomics in the precise diagnosis,treatment efficacy and prognosis prediction,and differential diagnosis of nasopharyngeal carcinoma,in order to provide a basis for clinical precise diagnosis and individualized treatment of nasopharyngeal carcinoma.

AIM To investigate the effects of ampelopsin-mediated autophagy and apoptosis of human cervical cancer SiHa cells.METHODS After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group,the 3-MA+ampelopsin group and the Z-VAD-FMK+ampelopsin group,the cells had their cell proliferation inhibition rate detected by MTT method.After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group and the 3-MA+ampelopsin group,the cells had their morphological changes observed under electron microscope and their apoptosis detected by Hoechst33258 and AnnexinV-FITC/PI staining.After 24 h corresponding administration and culture among the control group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group and the Z-VAD-FMK+ampelopsin group,the cells had their autophagy and ultrastructure observed by MDC method and transmission electron microscopy.After 12 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group,the 3-MA+ampelopsin group or control group,the Z-VAD-FMK (50 μmol/L) group,the ampelopsin (80 μmol/L) group,and the Z-VAD-FMK+ampelopsin group,the cells had their protein expressions of cleaved-PARP,cleaved-Caspase3,Bax,Bcl-2,Atg13,Beclin-1,LC3,and P62 detected by Western blot.RESULTS Compared with the control group,the ampelopsin group displayed enhanced proliferation inhibition of SiHa and C-33A cells (P<0.01).Compared with the ampelopsin group,the groups intervened with 3-MA+ampelopsin and Z-VAD-FMK+ampelopsin showed more significantly inhibited proliferation of the two cell lines (P<0.01),and decreased number of living cells.Compared with the ampelopsin group,the 3-MA+ampelopsin group showed increased bright blue fluorescence and apoptosis rate of SiHa cells (P<0.05),increased cleaved PARP,Bax,and P62 protein expressions (P<0.01),and decreased LC3Ⅱ/LC3Ⅰ ratio and Bcl-2 protein expression (P<0.01).Compared with the ampelopsin group,the Z-VAD-FMK+ampelopsin group demonstrated increased green dot fluorescence and number of autophagosomes and autopolysosomes,increased LC3Ⅱ/LC3Ⅰ ratio,Atg13 and Beclin-1 protein expression (P<0.05,P<0.01);and decreased protein expressions of P62,cleaved-PARP,cleaved-Caspase3 (P<0.05,P<0.01).CONCLUSION Being an antagonist of human cervical carcinoma SiHa cells,ampelopsin can induce autophagy and apoptosis of the cells through its key target on Beclin-1/Bcl-2.

AIM To investigate the effects of ampelopsin-mediated autophagy and apoptosis of human cervical cancer SiHa cells.METHODS After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group,the 3-MA+ampelopsin group and the Z-VAD-FMK+ampelopsin group,the cells had their cell proliferation inhibition rate detected by MTT method.After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group and the 3-MA+ampelopsin group,the cells had their morphological changes observed under electron microscope and their apoptosis detected by Hoechst33258 and AnnexinV-FITC/PI staining.After 24 h corresponding administration and culture among the control group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group and the Z-VAD-FMK+ampelopsin group,the cells had their autophagy and ultrastructure observed by MDC method and transmission electron microscopy.After 12 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group,the 3-MA+ampelopsin group or control group,the Z-VAD-FMK (50 μmol/L) group,the ampelopsin (80 μmol/L) group,and the Z-VAD-FMK+ampelopsin group,the cells had their protein expressions of cleaved-PARP,cleaved-Caspase3,Bax,Bcl-2,Atg13,Beclin-1,LC3,and P62 detected by Western blot.RESULTS Compared with the control group,the ampelopsin group displayed enhanced proliferation inhibition of SiHa and C-33A cells (P<0.01).Compared with the ampelopsin group,the groups intervened with 3-MA+ampelopsin and Z-VAD-FMK+ampelopsin showed more significantly inhibited proliferation of the two cell lines (P<0.01),and decreased number of living cells.Compared with the ampelopsin group,the 3-MA+ampelopsin group showed increased bright blue fluorescence and apoptosis rate of SiHa cells (P<0.05),increased cleaved PARP,Bax,and P62 protein expressions (P<0.01),and decreased LC3Ⅱ/LC3Ⅰ ratio and Bcl-2 protein expression (P<0.01).Compared with the ampelopsin group,the Z-VAD-FMK+ampelopsin group demonstrated increased green dot fluorescence and number of autophagosomes and autopolysosomes,increased LC3Ⅱ/LC3Ⅰ ratio,Atg13 and Beclin-1 protein expression (P<0.05,P<0.01);and decreased protein expressions of P62,cleaved-PARP,cleaved-Caspase3 (P<0.05,P<0.01).CONCLUSION Being an antagonist of human cervical carcinoma SiHa cells,ampelopsin can induce autophagy and apoptosis of the cells through its key target on Beclin-1/Bcl-2.

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

OBJECTIVES: To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome. RESULTS: Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment. CONCLUSIONS ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.
Child ; Extracorporeal Membrane Oxygenation ; Humans ; Hypertension, Pulmonary/therapy* ; Infant, Newborn ; Lung Diseases ; Persistent Fetal Circulation Syndrome/therapy* ; Retrospective Studies ; Treatment Outcome

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Humans ; Neoadjuvant Therapy/adverse effects* ; Paclitaxel/therapeutic use* ; Treatment Outcome ; Triple Negative Breast Neoplasms/pathology*