Immunoreactive Microenvironment Modulator GBP5 Suppresses Ovarian Cancer Progression by Inducing Canonical Pyroptosis.

Ovarian cancer has the highest mortality among gynecological malignancies, and exploring effective strategies to reverse the immunosuppressive tumor microenvironment in patients remains a pressing scientific challenge. In this study, we identified a pyroptosis-related protective factor, GBP5, which significantly inhibits the growth of ovarian cancer cells and patient-derived ovarian cancer organoids, impeding the invasion and migration of ovarian cancer cells. Results of immunohistochemistry and external single-cell data verification were consistent. Further research confirmed that GBP5 in ovarian cancer cell can induce canonical pyroptosis through JAK2/STAT1 pathway, thereby restraining the progression of ovarian cancer. Interestingly, in this study, we also discovered that ovarian cancer cells with high GBP5 expression exhibit increased expressions of CXCL9/10/11 in a co-culture assay. Subsequent immune cell infiltration analyses revealed the remodeling of immunosuppressive microenvironment in ovarian cancer patients, characterized by increased infiltration and polarization of M1 macrophages. External immunotherapy database analysis showed profound potential for the application of GBP5 in immunotherapy strategies for ovarian cancer. Overall, our study demonstrates that the protective factor GBP5 significantly inhibits ovarian cancer progression, triggering canonical pyroptosis through the JAK2-STAT1 pathway. Driven by its pro-inflammatory nature, it can also enhance M1 macrophages polarization and reverse immunosuppressive microenvironment, thus providing new insights for ovarian cancer treatment.

Psychological distress of cancer patients caused by treatment delay during the COVID-19 pandemic in China: A cross-sectional study.

OBJECTIVE: The currents study sought to explore the impact of treatment delay on the mental health for patients with cancer during the 2019 coronavirus disease (COVID-19) pandemic. METHODS: Travel restrictions were imposed in most areas of the country between 23 January 2020 and 25 February 2020 owing to the COVID-19 epidemic. Travel restrictions were lifted from 26 February 2020 to 12 March 2020. The number of new confirmed cases significantly reduced after 12 March 2020. Study participants, comprised of individuals from three distinct groups: (1) 835 cancer patients who attended Zhejiang Cancer Hospital between 26 February 2020 and 12 March 2020; (2) 185 healthy volunteers recruited between 26 February 2020 and 12 March 2020; (3) 168 cancer patients who attended the hospital during the non-epidemic period (after 12 March 2020). Two outcome measures including patients' posttraumatic stress responses and general psychological distress (GPD) were assessed using the Chinese versions of the Impact of Events Scale-Revised and the Kessler Psychological Distress Scale (K10). Treatment delay was assessed via counting the time interval from diagnosis to treatment initiation, or from planned treatment date to actual date of therapy. Communication satisfaction was evaluated via a self-report questionnaire. An independent sample t-test or Wilcoxon rank sum test was used for comparison. Statistical analysis included Chi-square test, Mann-Whitney test and multivariate logistic regression. RESULTS: All 1188 participants (835 patients with cancer and 185 controls during the outbreak, and 168 patients with cancer during the non-epidemic period) completed and submitted the questionnaires. A positive association was observed between treatment delays and increased GPD levels (OR 1.716; 95% confidence interval ,CI 1.254-2.348; p = 0.001) as well as posttraumatic stress disorder (PTSD) symptoms (OR: 1.545, 95% CI: (1.166-2.047), p = 0.002). Patients who reported good communication with their doctors showed a significantly lower risk of GPD (OR: 0.526, 95% CI (0.348-0.794), p = 0.002) and PTSD (OR: 0.683, 95% CI (0.490-0.951), p = 0.024) compared with patients who reported unsatisfactory communication or had no contact with their doctors. Multivariate logistic regression analysis showed that treatment at a local hospital, treatment delays and unsatisfactory or no communication with cancer-care professionals were significantly correlated with severe GPD and PTSD symptoms of patients (all p ≤ 0.05). CONCLUSION: The findings indicate that cancer patients who underwent treatment delays during the COVID-19 pandemic may become vulnerable to psychological distress. The results showed that effective communication with doctors and cancer-care professionals during outbreak significantly reduces GPD levels and PTSD symptoms.

Exploring the Protective Effect and Mechanism of Buddlejae Flos on Sodium Selenite-Induced Cataract in Rats by Network Pharmacology, Molecular Docking, and Experimental Validation.

Objective: Buddlejae Flos has a long history of utilization by humans to treat ophthalmic diseases. Although in vitro study revealed that it can be used for treating cataract, the bioactive components and the mechanism of efficacy remained unclear. This study aims to discover the bioactive components and mode of efficacy of Buddlejae Flos in cataract treatment. Methods: Several databases were screened for bioactive components and corresponding targets, as well as cataract-related targets. Using the String database, common targets were determined and utilized to construct protein-protein interactions (PPI). The drug-component-target-disease network map was drawn using Cytoscape software. R language was utilized to execute Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analysis. Molecular docking was done through Schrödinger Maestro software utilization. Luteolin's (LUT) effect on cataract induced by sodium selenite in rat pups was evaluated. Results: Six bioactive components with 38 common targets were identified as being associated with cataract. TP53, AKT1, EGFR, CASP3, TNF, ESR1, INS, IL6, HIF1A, and VEGFA were identified as core targets in PPI analysis, and the binding energy of LUT with AKT was the lowest. LUT has been demonstrated to significantly lower MDA levels, raise glutathione (GSH) levels, and boost the activity of antioxidant enzymes like GST, SOD, GPx, and CAT. After LUT treatment, TNF-a, IL-2, and IL-6 levels were significantly lowered. Bcl-2 mRNA expression levels and p-PI3K and p-AKT protein expression were significantly elevated. In contrast, caspase-3 and Bax mRNA expression levels were significantly decreased. Conclusion: This study demonstrates that LUT is a possible bioactive component that may be utilized for cataract treatment. Its mode of action includes oxidative stress suppression, reducing inflammation, and inhibiting apoptosis via regulating the PI3K/AKT single pathway.

[Study on present status of ICU in county-level general hospitals of Henan Province].

OBJECTIVE: To investigate the present status of intensive care unit (ICU) in the county-level general hospitals of Henan Province and provide basis for improving the construction level and rational allocation of medical resources of ICU. METHODS: According to The guidelines for the construction and management of critical care medicine (trial implementation) issued by National Health Commission (NHC) (hereinafter referred as the guidelines), a cross-sectional survey was conducted on the present status of ICU in 93 county-level general hospitals in Henan Province in 2018 by using a self-designed questionnaire concerning this topic. The survey included the basic information of ICU (establishment time, organization and management mode, development of special departments in ICU, construction of key disciplines), scale and staffing allocation and training, and the equipment and technology development situation in ICU. RESULTS: The basic aspects of ICU situation were as follows: firstly, the establishment time: the ICU of county-level general hospitals in Henan Province started relatively late. The survey showed that all the 93 hospitals had set up ICU, of which the earliest was the ICU of Xunxian People's Hospital in 1989, only 4 county-level general hospitals established their ICUs before 2000, and 34 before 2009. Secondly, the management mode: the proportion of ICU closely managed was accounting for 68.82% (64/93), while semi-open management was 18.28% (17/93), and 12.90% (12/93) hospitals still adopted the open management mode. Thirdly, development of specialized ICU and construction of key disciplines: comprehensive ICUs were founded in 86 hospitals, and the proportions of specialized ICUs such as neonatal ICU, emergency ICU and coronary heart disease care unit (CCU) were higher than other kinds of special department; the ICUs of 8 hospitals were the key discipline of Henan Provincial Health Commission, and the ICUs of 9 hospitals were the discipline of Municipal Health Commission. Scale and staffing of ICU: a total of 2 189 ICU beds were opened in 93 county-level general hospitals. The utilization rate reaching the targets of ICU beds and the compliance rate of ICU bed area per bed were relatively high, 76.34% and 80.64%, while the compliance rates of ICU doctors/ICU beds, ICU nurses/ICU beds were low, which were 8.60% and 7.52% respectively, indicating that the clinicians and nursing facilities were insufficient. There were 1 tertiary hospital, 76 secondary-A hospitals and 16 secondary-B hospitals in this survey. Compared with secondary-B hospitals in the total number of beds (sheets: 922.22±285.99 vs. 636.75±258.84) and ICU beds (sheets: 25.28±21.15 vs. 14.63±6.89), the secondary-A hospitals were significantly higher (all P < 0.01), and the rate of bed use compliance of secondary-A hospitals was significantly higher than that in secondary-B hospitals [81.6% (62/76) vs. 50.0% (8/16), P < 0.01]. In terms of staffing, the proportion of clinicians and nurses with elementary titles was the highest, the proportion of full-time senior professional titles was relatively low, the proportion of doctors with bachelor's degree was the highest, and that of nurses with junior college degree was the highest. In personnel training, the hospitals surveyed had sent the doctors and nurses mostly to participate in the continuing education and training of critical care medicine at or above the provincial level for 745 person-times and 1 156 person-times, and there were in the mean for 8 and 12 person-times in each hospital, respectively. In terms of equipment configuration and technology development of ICU, mostly the equipment in ICU of county-level general hospitals consisted of microinjection pump, monitor, infusion pump, invasive ventilator, expectorant machine, etc. but the overall equipment was insufficient. Although an extracorporeal membrane oxygenation (ECMO) equipment was introduced in one hospital, it had not been carried out clinically. All county-level general hospitals in Henan Province had set up ICUs, but there were gaps between the compliance rates of many indicators and the requirements of the guidelines, and the medical personnel and equipment were relatively insufficient. CONCLUSIONS: The ICUs of county-level general hospitals in Henan Province have developed rapidly in recent years, but there is still much room for improvement.

Enteral Nutrition Support Does Not Improve PNI in Radiotherapy Patients with Locally Advanced Esophageal Cancer.

OBJECTIVE: The assessment of prognostic nutritional index (PNI) before and during radiotherapy is an important parameter for the prognosis in patients with cancer. In this study, enteral tube feeding (ETF) was used during radiotherapy in patients with EC. Dynamic changes of various nutritional indicators (including PNI) were monitored. METHODS: Patients with EC who underwent radiotherapy between June 2016 and July 2017 were enrolled. ETF was performing with the energy of 25 kcal × kg/d. Nutritional status were evaluated. Least significant difference (LSD) was used for multiple comparisons between groups. RESULTS: A total of 148 patients were admitted, including 51 patients fed via ETF. For patients who were not scheduled to nutritional support, significant difference were observed in albumin (ALB) (P < 0.001), prealbimnin (PA) (P = 0.05) and PNI (P < 0.001) compared to levels before radiotherapy. In the patients fed via enteral tube, no significant difference were found in weight, BMI, ALB, retinol binding protein (RBP) and PA before and after radiotherapy, while PNI significantly decreased (P < 0.001). CONCLUSION: After preforming ETF with the energy of 25 kcal × kg/d in patients with EC during radiotherapy, PNI, the key nutritional index reflecting prognosis, significantly decreased.