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IntroductionObesity is a major risk factor in the development of endometrial cancer in young patients in the reproductive age group. Fertility sparing treatment is a viable option for a select group of patients with early endometrial cancer, and involves systemic and intra-uterine hormonal therapy. Weight loss has been associated with improved outcomes in this group. Bariatric surgery has been shown to be the most effective and durable method of weight loss in obese patients. However, there is a paucity of data studying the benefit of bariatric surgery as part of fertility sparing management.MethodsWe present a retrospective case series of five patients who are undergoing fertility sparing treatment for early endometrial cancer, who also underwent bariatric surgery for treatment of obesity and related comorbidities. We aim to show early regression of endometrial cancer for all the patients and also report on the other health benefits of bariatric surgery.ResultsAll five patients in this series achieved regression of endometrial cancer within six months of undergoing bariatric surgery. They also achieved significant weight loss and three patients with obesity-related comorbidities had remission of these conditions. One patient conceived via in-vitro fertilization and delivered a healthy baby.Conclusion/ImplicationsPatients on fertility sparing treatment for endometrial cancer who underwent bariatric surgery achieved early cancer regression within six months, significant weight loss and resolution of obesity related comorbidities. Bariatric surgery could be a promising component of fertility sparing management for obese patients. Long term, prospective studies are required to confirm the benefits reported in this series.

Background Previous studies had showed that Apelin 13 could protect against apoptosis induced by ischemic/reperfusion (I/R). However, the mechanisms whereby Apelin 13 protected brain I/R remained to be elucidated. The present study was designed to determine whether Apelin 13 provided protection through AMPK/GSK-3β/Nrf2 pathway. Methods In vivo, the I/R model was induced and Apelin 13 was given intracerebroventricularly 15 min before reperfusion. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured. For in vitro study, PC12 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Protein levels were investigated by western blotting. Results The results showed that Apelin 13 treatment significantly reduced infarct size, improved neurological outcomes, decreased brain edema, and inhibited cell apoptosis, oxidative stress, and neuroinflammation after I/R. Apelin 13 significantly increased the expression of Nrf2 and the phosphorylation levels of AMPK and GSK-3β. Furthermore, in cultured PC12 cells, the same protective effects were also observed. Silencing Nrf2 gene with its siRNA abolished the Apelin 13’s prevention of I/R-induced PC12 cell injury, oxidative stress, and inflammation. Inhibition of AMPK by its siRNA decreased the level of Apelin 13-induced Nrf2 expression and diminished the protective effects of Apelin 13. The interplay relationship between GSK-3β and Nrf2 was also verified with relative overexpression. Using selective inhibitors, we further identified the upstream of AMPK/GSK-3β/Nrf2 is AR/Gα/PLC/IP3/CaMKK. Conclusions In conclusion, the previous results showed that Apelin 13 protected against I/R-induced ROS-mediated inflammation and oxidative stress through activating the AMPK/GSK-3β pathway by AR/Gα/PLC/IP3/CaMKK signaling, and further upregulated the expression of Nrf2-regulated antioxidant enzymes.

Background Colorectal cancer (CRC) patients undergoing surgery are at a high risk of developing surgical site infections (SSIs), which contribute to increased morbidity, prolonged hospitalization, and escalated healthcare costs. Understanding the incidence, risk factors, and impact of SSIs is crucial for effective preventive strategies and improved patient outcomes. Methods This retrospective study analyzed data from 431 CRC patients who underwent surgery at Huangshan Shoukang Hospital between 2014 and 2022. The clinical characteristics and demographic information were collected. The incidence and impact of SSIs were evaluated, and independent risk factors associated with SSIs were identified using multivariable logistic regresison. A nomogram plot was constructed to predict the likelihood of SSIs occurrence. Results The overall incidence rate of SSIs was 7.65% (33/431). Patients with SSIs had significantly longer hospital stays and higher healthcare costs. Risk factors for SSIs included elevated Body Mass Index (BMI) levels (odds ratio, 1.12; 95% CI, 1.02—1.23; P  = 0.017), the presence of diabetes (odds ratio, 3.88; 95% CI, 1.42 – 9.48; P  = 0.01), as well as specific surgical factors such as open surgical procedures (odds ratio, 2.39; 95% CI [1.09; 5.02]; P  = 0.031), longer surgical duration (odds ratio, 1.36; 95% CI [1.01; 1.84]; P  = 0.046), and the presence of a colostomy/ileostomy (odds ratio, 3.17; 95% CI [1.53; 6.62]; P  = 0.002). Utilizing multivariable regression analysis, which encompassed factors such as open surgical procedures, the presence of diabetes and colostomy/ileostom, the nomogram plot functions as a visual aid in estimating the individual risk of SSIs for patients. Conclusions Risk factors for SSIs included higher BMI levels, the presence of diabetes, open surgical procedures, longer surgical duration, and the presence of colostomy/ileostomy. The nomogram plot serves as a valuable tool for risk assessment and clinical decision-making.

D‐1553 is a small molecule inhibitor selectively targeting KRASG12C and currently in phase II clinical trials. Here, we report the preclinical data demonstrating antitumor activity of D‐1553. Potency and specificity of D‐1553 in inhibiting GDP‐bound KRASG12C mutation were determined by thermal shift assay and KRASG12C‐coupled nucleotide exchange assay. In vitro and in vivo antitumor activity of D‐1553 alone or in combination with other therapies were evaluated in KRASG12C mutated cancer cells and xenograft models. D‐1553 showed selective and potent activity against mutated GDP‐bound KRASG12C protein. D‐1553 selectively inhibited ERK phosphorylation in NCI‐H358 cells harboring KRASG12C mutation. Compared to the KRAS WT and KRASG12D cell lines, D‐1553 selectively inhibited cell viability in multiple KRASG12C cell lines, and the potency was slightly superior to sotorasib and adagrasib. In a panel of xenograft tumor models, D‐1553, given orally, showed partial or complete tumor regression. The combination of D‐1553 with chemotherapy, MEK inhibitor, or SHP2 inhibitor showed stronger potency on tumor growth inhibition or regression compared to D‐1553 alone. These findings support the clinical evaluation of D‐1553 as an efficacious drug candidate, both as a single agent or in combination, for patients with solid tumors harboring KRASG12C mutation. D‐1553 is a novel and potent inhibitor of KRASG12C. D‐1553 shows an inhibitory effect on the RAS–MEK signaling pathway. D‐1553 has antitumor activity in vitro and in in vivo models with KRASG12C mutation.

Deep learning (DL) enabled liquid-based cytology has potential for cervical cancer screening or triage. Here, we develop a DL model using whole cytology slides from 17,397 women and test it on 10,826 additional cases through a three-stage process. The DL model achieves robust performance across nine hospitals. In a multi-reader, multi-case study, it outperforms cytopathologists’ sensitivity by 9%. Reading time significantly decreases with DL assistance (218s vs 30s; p  < 0.0001). In community-based organized screening, the DL model’s sensitivity matches that of senior cytopathologists (0.878 vs 0.854; p  > 0.999), yet it has reduced specificity (0.831 vs 0.901; p  < 0.0001). Notably, hospital-based opportunistic screening shows that junior cytopathologists with DL assistance significantly improve both their sensitivity and specificity (0.857 vs 0.657, 0.840 vs 0.737; both p  < 0.0001). When triaging human papillomavirus-positive cases, DL assistance exhibits better performance than junior cytopathologists alone. These findings support using the DL model as an assistance tool in cervical screening and case triage. Cytology is commonly used for cervical cancer screening or triage. Here, the authors used deep learning to develop a liquid-based cytology screening approach to detect cervical cancer in both community and hospital-based settings.

Background The proper use of personal protective equipment (PPE) can save lives and prevent major injuries among blue-collar workers who are at heightened risk of workplace accidents. Yet, the non-use or improper use of PPE is not uncommon. Despite academic interest in the issue, there is an absence of accessible and theory-driven PPE surveys for blue-collar workers. This study seeks to develop a simple language Capability, Opportunity, Motivation – Behaviour (COM-B) survey for PPE wearing among blue-collar workers. Methods A combined deductive and inductive approach to item generation was adopted. This included referencing existing research and surveys and working closely and iteratively with blue-collar workers and their managers to develop the survey. A 14-item survey based on five factors of the COM-B model was developed and tested with 867 multi-national male blue-collar workers. Additional questions on demographics and PPE compliance intentions were asked. Structural Equation Modelling (SEM) and Confirmatory Factor Analyses (CFA) were conducted to assess the model fit and provide evidence for the reliability and validity of the survey. Results Results support the internal consistency of our survey subscales (Cronbach’s α coefficients > 0.90), demonstrate good model fit (χ² (104) = 24.963, χ²/df = 0.240, CFI = 1.005, TLI = 1.007, RMSEA = 0.000), and provide initial evidence for the validity of the survey by replicating past findings. COM-B factors of Physical Capability (β = 0.47, p  < .01) and Psychological Capability (β = 0.69, p  < .01) significantly predicted blue-collar workers’ intentions to keep their full PPE on properly during their shift. Conclusions Despite Limitations resulting from the use of a testing sample from a single company, this short 14-item survey is accessible, theory-driven, and directly tested with multi-national blue-collar workers. Future work with blue-collar workers from different industries and settings can confirm the generalisability of the survey. A reliable and valid survey can lead to the development of effective and evidence-based interventions for PPE compliance among blue-collar workers that can prevent major injuries and save lives.

Inorganic ferroelectrics have long dominated research and applications, taking advantage of high piezoelectric performance in bulk polycrystalline ceramic forms. Molecular ferroelectrics have attracted growing interest because of their environmental friendliness, easy processing, lightweight, and good biocompatibility, while realizing the considerable piezoelectricity in their bulk polycrystalline forms remains a great challenge. Herein, for the first time, through ring enlargement, a molecular ferroelectric 1‐azabicyclo[3.2.1]octonium perrhenate ([3.2.1‐abco]ReO4) with a large piezoelectric coefficient d33 up to 118 pC/N in the polycrystalline pellet form is designed, which is higher than that of the parent 1‐azabicyclo[2.2.1]heptanium perrhenate ([2.2.1–abch]ReO4, 90 pC/N) and those of most molecular ferroelectrics in polycrystalline or even single crystal forms. The ring enlargement reduces the molecular strain for easier molecular deformation, which contributes to the higher piezoelectric response in [3.2.1‐abco]ReO4. This work opens up a new avenue for exploring high piezoelectric polycrystalline molecular ferroelectrics with great potential in piezoelectric applications. A high piezoelectric molecular ferroelectric 1‐azabicyclo[3.2.1]octonium perrhenate ([3.2.1‐abco]ReO4) is precisely designed by the novel chemical design strategy of ring enlargement. Intriguingly, its polycrystalline pellet can show a piezoelectric coefficient d33 as large as 118 pC/N, larger than that of the parent 1‐azabicyclo[2.2.1]heptanium perrhenate ([2.2.1–abch]ReO4) and those of most polycrystalline or even single‐crystal molecular ferroelectrics.

Background Cardiac rehabilitation (CR) can improve the prognosis of cardiovascular diseases. Healthcare providers’ recommendations play a key role in promoting patient participation in CR. This study aimed to assess healthcare professionals’ beliefs of CR in China, explore the current status of CR recommendations to patients, and identify the factors influencing their recommendation behavior. Methods A cross-sectional survey was conducted among cardiovascular doctors, nurses, rehabilitation therapists and general practitioner from healthcare institutions across the country. A total of 1,120 valid questionnaires were collected. The survey included demographic information, the Chinese version of the Recommending Cardiac Rehabilitation (ReCaRe) scale to assess beliefs regarding CR, CR resources, knowledge of CR, and CR recommendation behavior. Binary logistic regression was performed to identify the factors influencing CR recommendation behavior. Results The total score of the ReCaRe scale was 60.80 ± 7.36, with the perceived severity and susceptibility scoring 3.98 ± 0.60, perceived service accessibility at 2.72 ± 0.96, and the perceived benefits and barriers 4.13 ± 0.56. It was reported by 56.5% of healthcare providers that they had recommended CR to patients. However, only 34.6% of participants were familiar with the specific details of CR. It was expressed by 86.0% of healthcare providers that there is a need for more CR resources and training. The predictive factors for healthcare professionals’ CR recommendation behavior included familiarity with CR content and the five CR prescriptions, professional title, availability of CR services, hospital type, position, department and age. Conclusions There is an urgent need to provide healthcare professionals with more resources and training to deepen their understanding of CR, while also addressing the utilization and accessibility of CR services, in order to enhance their CR recommendation behavior.

Hypertrophic obstructive cardiomyopathy (HOCM) can bring a high risk of sudden cardiac death in young people. It is particularly urgent to understand the development and mechanism of HOCM to prevent unsafe incidents. Here, the comparison between pediatric and adult patients with HOCM has been performed to uncover the signaling mechanism regulating pathological process through histopathological analysis and immunohistochemical analysis. We found SMAD proteins played an important role during myocardial fibrosis for HOCM patients. In patients with HOCM, Masson and HE staining showed that myocardial cells were diffusely hypertrophied with obvious disorganized myocardial fiber alignment, and myocardial tissue was more damaged and collagen fibers increased significantly, which come early in childhood. Increased expressions of SMAD2 and SMAD3 contributed to myocardial fibrosis in patients with HOCM, which happened early in childhood and continued through adulthood. In addition, decreased expression of SMAD7 was closely related to collagen deposition, which negatively expedited fibrotic responses in patients with HOCM. Our study indicated that the abnormal regulation of SMAD signaling pathway can lead to severe myocardial fibrosis in childhood and its fibrogenic effects persist into adulthood, which is a crucial factor in causing sudden cardiac death and heart failure in HOCM patients.

Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo . Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-β and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8 + T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8 + T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8 + T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.