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*

In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.

In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.

Background::Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.Methods::Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.Results::The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking.Conclusion::With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Cancer is one of the leading causes of morbidity and mortality worldwide. Due to population aging, lifestyle variation and other factors, the morbidity and mortality of cancer continue to rise in China, resulting in a serious public health problem threating people's health. In response to this increasingly serious problem, tremendous efforts have been made in China, including the development of a series of policies and measures for specific needs of cancer prevention and treatment. Currently, China's strategy to reduce the disease burden of cancer mainly focuses on primary and secondary prevention. This paper summarizes the current status of disease burden of cancer and the performance of three-grade cancer prevention in China.

Objective:To evaluate the reoperation of abdominal metastasis after liver resection for hepatocellular carcinoma (HCC).Methods:The data of 2748 patients with liver cancer undergoing surgical resection at the Department of Hepatobiliary and Pancreatic Surgery of Li Huili Hospital of Ningbo Medical Center from January 2010 to January 2022 were retrospectively screened. A total of 19 patients with abdominal metastases after liver resection undergoing reoperation were enrolled, which were all males with a median age of 53 years (27 to 68). The surgical procedures and diagnosis for abdominal metastases were recorded, and the recurrence and survival of patients were followed up.Results:During the follow-ups of initial resection of HCC, 10 patients were diagnosed with postoperative abdominal metastasis by enhanced CT, and seven patients were diagnosed by MRI. MRI and PET/CT were negative in two patients. Abdominal metastasis was found during reoperation in one case and liver transplantation in the other case due to postoperative liver recurrence. All 19 patients successfully underwent radical resection of abdominal metastases. Eighteen patients underwent open surgery and one underwent laparoscopic surgery. Among them, nine cases underwent simple metastases resection, six combined liver resection, one combined liver resection and right hemicolectomy, one combined partial rectal resection, one combined partial small bowel resection, and one combined liver transplantation. The 1-year, 3-year, and 5-year disease-free survival rates were 26.3%, 15.8%, 10.5%, respectively. The 1-year, 3-year, and 5-year overall survival rates were 94.7%, 26.3%, 15.8%, respectively. Three patients are currently surviving disease-free for 154.3 months, 67.3 months, and 33.4 months, respectively. These three patients all had single abdominal metastase and did not receive any targeted or immune treatments after surgery.Conclusion:For patients with localized or single abdominal metastases after HCC surgery, reoperation for metastases can bring survival benefits.

Objective:To investigate the risk factors for postoperative early recurrence of patients with single large hepatocellular carcinoma (HCC) (tumor diameter≥5cm).Methods:Clinical data of 135 single large HCC patients who underwent radical resection from Jan 2015 to Sep 2020 in Ningbo Medical Centre Lihuili Hospital were analyzed.Results:Seventy-five HCC patients suffered recurrence,among those 42 patients had early recurrence(within 12 months). Multivariate analysis showed that alpha-fetoprotein (AFP)≥400 ng/ml ( OR=3.510,95% CI: 1.528-8.064; P=0.003) and tumor microvascular invasion (MVI) ( OR=2.769,95% CI: 1.143-6.706; P=0.024) were independent risk factors for early recurrence of single large hepatocellular carcinoma. Survival analysis showed that early recurrence risk factors significantly reduced recurrence free survival (RFS)(AFP≥400 ng/ml, χ 2=23.038, P<0.001; MVI positive , χ 2=10.554, P=0.001) and overall survival (OS) (AFP≥400 ng/ml, χ 2=14.336, P<0.001; MVI positive, χ 2=10.481, P=0.001) in single large hepatocellular carcinoma patients. Conclusion:AFP≥400 ng/ml and MVI positive are independent risk factors for postoperative early recurrence in single large hepatocellular carcinoma patients.

Objective:To analyze the prognostic factors affecting salvage liver transplantation (SLT).Methods:The clinical data of 97 patients undergoing liver transplantation in the Ningbo Medical Centre Lihuili Hospital from January 2012 to May 2022 were retrospectively analyzed, including 84 males and 13 females, aged (53.6±7.4) years. Among them, 33 patients underwent primary liver transplantation (PLT) and 64 underwent SLT. SLT patients were subdivided into the groups within the Milan criteria (SLT-A, n=35) and beyond the Milan criteria (SLT-B, n=29), according to whether the Milan criteria were met at first hepatectomy. Clinicopathological and prognostic data were subsequently analyzed. Results:The tumor number ( χ2=16.03, P<0.001), microvascular invasion (MVI) ( χ2=10.97, P=0.004), recurrence rate ( χ2=9.31, P=0.010), recurrence-free survival (RFS, F=14.05, P=0.001) and overall survival (OS, F=17.27, P<0.001) were significantly different among the three groups. RFS ( P=0.047) and OS ( P=0.012) in PLT group were better than those in SLT-B group. RFS ( P=0.007) and OS ( P=0.024) in SLT-A group were also better than those in SLT-B group. The multivariate analysis indicated that beyond the Milan criteria at first hepatectomy was an independent risk factor for RFS ( HR=4.378, 95% CI: 1.393-13.756, P=0.011) and OS ( HR=5.391, 95% CI: 1.428-20.352, P=0.013) in patients undergoing SLT, and MVI positive ( HR=4.042, 95% CI: 1.137-14.368, P=0.031) was an independent risk factor for RFS in patients undergoing SLT. Conclusion:Patients beyond the Milan criteria at first hepatectomy and MVI positive showed a poorer prognosis after SLT. Whether the Milan criteria should be the gold standard for SLT as well as for PLT needs further study.

Objective To analyze the effect of HIV/AIDS patients receiving antiretroviral therapy (ART) for the first time in Jiangyin, and to provide a reference for further improvement of Jiangyin's AIDS antiretroviral treatment. Methods The historical cards and related information in the treatment management database of Jiangyin City's cases who received ART for the first time from 2005 to 2019 were collected and statistically analyzed. The changes in viral load and CD4+ T lymphocytes (CD4 cells) before and after treatment were compared. Results Among 652 patients receiving ART, 507 cases (77.76%) were successful in virological treatment. The median natural change rate of annual average CD4 cell count was 90.8 cells/μL/year (χ²=37.915, P<0.05; H=9.781, P<0.05). There were statistically significant differences in virological treatment and immune recovery between different age groups (χ²=10.713, P<0.05; H =10.394, P<0.05) and different baseline CD4 count layers. The results showed that age and baseline CD4 value were the influencing factors of treatment effect. Conclusion Age and baseline CD4 value can affect the effect of ART treatment. The older the age and the lower the baseline CD4 value, the worse the virological efficacy and the recovery effect of CD4 cells. It is suggested that the infected patients should be involved in ART in time, which is conducive to shorten the time of initial treatment and further improve the effect of antiviral treatment.