OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

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*

Objective:Pediatric chronic sinusitis （CRS） is a common disease within the field of otolaryngology-head and neck surgery. Due to the immaturity of sinus development and immune competence in children, its etiology and pathophysiology are complex, and its clinical features and outcomes differ significantly from those in adult patients. Currently, there are issues in the diagnosis and treatment of pediatric CRS, particularly in areas such as antibiotic use and surgical interventions, owing to a lack of sufficient attention. In recognition of this, the Chinese Rhinopathy Research Cooperation Group developed this expert consensus based on a systematic review of the latest literatures from both domestic and international sources, with reference to the latest evidence-based medical evidence worldwide, and in combination with their own clinical experience. The consensus covers various aspects including epidemiology, predisposing factors, pathophysiology, diagnosis and differential diagnosis, as well as treatment strategies such as medical therapy and surgical intervention. It aims to standardize the clinical diagnosis and treatment of pediatric CRS, improve clinical efficacy and patient satisfaction, reduce clinical expenditures, and decrease the occurrence of adverse reactions.
Humans ; Sinusitis/therapy* ; Chronic Disease ; Child ; Consensus ; Anti-Bacterial Agents/therapeutic use*

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth

The malignant degree of cholangiocarcinoma is high, and the early diagnosis is difficult. The vast majority of patients are unresectable when they are diagnosed. The patients have low quality of life and short survival cycle. Traditional radiotherapy and chemotherapy have poor efficacy and lead to side effects, and thus lack effective control measures for cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography (ERCP) is an important method for diagnosing and treating biliary tract diseases. Photodynamic therapy (PDT) is a new local treatment for cholangiocarcinoma. In recent years, ERCP-mediated PDT treatment of cholangiocarcinoma has gradually emerged. ERCP-mediated PDT can effectively relieve the symptoms of patients with cholangiocarcinoma, improve the patients' quality of life, prolong the survival cycle, and is expected to become a new treatment for cholangiocarcinoma.
Bile Duct Neoplasms ; diagnosis ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; diagnosis ; Cholangiopancreatography, Endoscopic Retrograde ; Humans ; Photochemotherapy ; Quality of Life

Objective:To test the validity and reliability of the Perceived Stress Scale-14 items (PSS-14) applied in cancer survivors.Methods:Totally 652 cancer survivors (patients who had finished active treatments and were in convalescence) were selected and a field questionnaire survey was conducted among them.Exploratory factor analysis and confirmatory factor analysis were performed to test the construct validity of PSS-14.Correlation between the two dimensions (discriminant validity) and correlation between stress and quality of life were analyzed to further test its validity.The intemal consistency reliability,split-half reliability,retest reliability and sensitivity analysis were adopted to test the reliability of PSS-14.Results:Two common factors were extracted in the exploratory factor analysis.The cumulative percentage of variance explained was 60.8％.The index of confirmatory factor analysis were:TLI =0.92,CFI =0.93,SRMR =0.07,RMSEA =0.08.The correlation coefficient between the two dimensions of PSS-14 was-0.16 (P ＜0.001).The correlation coefficients between the score of PSS-14 and each dimension of EORTC QLQ-C30 were 0.24-0.55 (P ＜ 0.001).The Cronbach α coefficients of the whole scale and the two dimensions named "perceived coping ability" and "perceived distress" were 0.78,0.91 and 0.88 respectively.After the scale was split into two parts,the Cronbach α coefficients of each part were 0.66 and 0.60.The Spearman-Brown coefficient was 0.79.The Guttman split-half coefficient was 0.79.After one item was removed from the scale each time,the Cronbach a coefficients of the remaining items varied from 0.75 to 0.77.The retest reliability of the whole scale and the two dimensions were 0.89,0.86 and 0.85 respectively.Conclusion:PSS-14 shows favorable validity and reliability,suggesting the utility to assess stress of cancer survivors as a self-administered inventory.

Aim To study the effect of estrogen on the migration of breast cancer cells and the possible underlying mechanisms.Methods Human breast cancer cell lines MCF-7(estrogen receptor, ER+) and MDA-MB-468(ER-) were employed as a model system.Cells were treated with E2 and pretreated with CANP inhibitor(calpeptin)where needed.Wound-healing assay was applied to evaluate cell migration, Western blot assay was performed to observe protein level, and fibronectin expression was silenced by specific siRNA transfection.Results ① Treatmentof MCF-7 and MDA-MB-468 cellswith E2(50 nmol·L-1) increased cell migration by(51.55±5.50) ％(P<0.01)and (40.78±4.78)％(P<0.05), respectively;② E2 significantly up-regulated the expression of FN protein in MCF-7 and MDA-MB-468 breast cancer cells, which was 2.11 times(P<0.05)and 1.86 times(P<0.01), respectively;③ Pretreatment with calpeptin(10 μmol·L-1) decreased E2-induced cell migration by (49.55±6.44)％(P<0.05) in MCF-7 and(36.85±4.40)％ (P<0.01)in MDA-MB-468 cells;④ Calpeptin pretreatment inhibited E2-induced fibronectin up-regulation by(80.12±4.55)％ and(78.84±5.70) ％(P<0.01), respectively;⑤ Knockdown of FN with siRNA suppressed cell E2-induced migration by(40.65±5.80)％(P<0.01)in MCF-7 and(40.88±6.02)％(P<0.05)in MDA-MB-468 cells.Conclusion E2 stimulates the migration of breast cancer cells with or without ER expression and a calpain-FN signaling pathway may be involved in the E2 action.

Objective:To explore the effects of protoporphyrin Ⅸ (PpⅨ)-mediated photodynamic therapy (PDT) on induction of apoptosis and death in colon cancer cell and the underlying mechanisms.Methods:The cell killing effect of PDT on HCT116 cell was determined by cell counting kit (CCK).The cells were divided into a control group,a single light group,a single PpⅨ group,and a PDT group.Hoechst 33342 and flow cytometry was used to assess the cell apoptosis.Western blot was employed to analyze the expressions ofbd-2,bax,and caspase-3.Reactive oxygen species (ROS) was detected by flow cytometry.Results:The viability of HCT116 cell was decreased gradually with the increase of irradiation dose (P<0.05).Compared to the other 3 groups,ROS production,the number of apoptotic cells and the protein expressions ofbax and caspase-3 in PDT group increased,while bcl-2 expression was decreased (P<0.05).Conclusion:PpⅨ-mediated PDT can enhance the apoptosis in HCT116 cell,which may be related to mitochondrial apoptosis pathway.

Objective: To study the coping styles and its relationship with quality of life among part of the female breast cancer patients in Shanghai in 2014. Methods: In August of 2014, 1-3 block groups affiliated to Shanghai Cancer Rehabilitation Club were selected from each of the 17 districts of Shanghai by convenient sampling method. Respondents were recruited from these block groups via putting up posters in the community or top three hospitals nearby. The inclusion criteria were as follows: female, aged from 18 to 80 years old; the initial diagnosis or primary tumor was breast cancer, and active treatments including surgery, radiotherapy and chemotherapy were finished; capable of basic reading and comprehension, and there was no communication disorder; daily activities were not limited, and with no mental disorder or dysgnosia. Totally 2 205 respondents were included. Questionnaire survey was conducted to collect the information of demographic characteristics, disease characteristics, result of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and result of the Ways of Coping Inventory-Cancer Version (WOC-CA). 1 968 valid questionnaires were withdrawn. The results of respondent characteristics and WOC-CA were under descriptive analysis, and the differences of coping styles among groups of different demographic characteristics were compared using t test. In addition, we analyzed the correlation between respondents' coping styles and quality of life using partial correlation analysis. Results: The average age of the 1 968 respondents was (58.7±7.4) years old, and BMI was (24.4±5.4) kg/m². The score of positive coping styles was 2.04±0.41, and the score of negative coping styles was 1.79±0.33. The scores of Physical Functioning (PF), Role Functioning (RF), Cognitive Functioning (CF), Emotional Functioning (EF), Social Functioning (SF), and Global Health (GH) were 83.40±12.18, 90.80±15.92, 80.72±16.29, 84.67±15.19, 80.99±20.91, 65.27±21.21, respectively. Positive coping styles correlated with PF, EF, and GH positively, and the correlation coefficients were separately 0.581 (P=0.046), 0.593 (P=0.045), 0.770 (P<0.001). Negative coping styles correlated with RF, CF, EF, and SF negatively, and the correlation coefficients were separately-0.672 (P=0.021),-0.815 (P=0.005),-0.121 (P<0.001),-0.123 (P<0.001). Conclusion Part of the female breast cancer patients in Shanghai in 2014 mainly adopted positive coping styles, and in general the positive coping styles correlated with quality of life positively and negative coping styles correlated with quality of life negatively.

Objective: To explore the characteristics of acute otitis media(AOM) in children in Beijing and its correlation with meteorological factors. Methods: Data were collected in 2011-2013 in the Otolaryngology Department of Capital Institute of Pediatrics. AOM in children with relevant information, such as age, sex and season, with the same period of the Beijing municipal meteorological data (the average temperature, average pressure, average wind speed, humidity and PM2.5) were compared to analysis the relationship of meteorological environmental parameters and the onset of AOM in children. Results: Annual morbidity of AOM was 7 589, 8 245, 7 242 respectively, no obvious difference(P=0.761). It was noted that one peak could be seen in December, and a valley in February, followed by August. Summer was less than the other three seasons (P<0.05). The morbidity of AOM had a small peak within one year after birth, then reached peak at the age of about 4, and then reduced gradually. In different age groups, male patients were higher than those of female. The incidence of AOM was positively correlation tendency with air pressure and PM2.5 (r=0.333, 0.093, P=0.000, 0.002), which was negatively correlation tendency with daily temperature or humidity (r=-0.327, -0.195, P=0.000, 0.000). Conclusions The incidence of AOM of children in Beijing changes with age, and has obvious seasonal variation. There may be some correlation between the meteorological factors and the incidence of AOM in children.