Enhancing thermal transport of epoxy composites with vertically aligned graphene in situ grown on the thermal interface.

The escalating demands for miniaturization, integration, and portability in electronic devices have underscored the criticality of efficient heat dissipation. The utilization of high-performance thermal interface materials (TIMs) to fill the gaps between contacting surfaces holds significant potential for enhancing heat transfer efficiency. Herein, we successfully enhance the thermal properties of the epoxy composite TIM by integrating in situ grown vertically aligned graphene on the metal surface using radio frequency plasma-enhanced chemical vapor deposition (RF-PECVD). To investigate the effect of vertical graphene on epoxy, the sandwich structure of copper/vertical graphene-epoxy/copper (Cu/VG-EP/Cu) is fabricated by incorporating epoxy resin. The experimental results demonstrate that the thermal conductivity of VG-EP reaches 2.06 W m-1 K-1 and achieves an impressive 1215% maximum enhancement. Furthermore, the numerical simulation findings show that vertical graphene consistent with the temperature gradient exhibits the highest heat transfer efficiency. This work presents an in-depth study of vertically aligned graphene within the epoxy resin, highlighting the advantages of vertically aligned fillers and offering novel perspectives for the advancement of TIMs.

Effect of sarcopenia on liver cirrhosis with complicating oesophageal and gastric varices after endoscopic therapy.

Several investigators have reported that sarcopenia is common in patients with liver cirrhosis. However, few studies have probed the association between sarcopenia and liver cirrhosis complicated with oesophageal and gastric variceal bleeding (LC-EGVB). We aimed to investigate the impact of sarcopenia on rebleeding after endoscopic therapy in patients with LC-EGVB. Computed tomography (CT) radiographs from the third lumbar vertebra were selected to analyse body composition, including skeletal muscle tissue, visceral and subcutaneous adipose tissue using SliceOmatic software. Sarcopenia was defined using validated cutoff values for patients with liver cirrhosis: 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. A total of 187 patients with LC-EGVB and 309 controls were included in this study. The rate of sarcopenia in controls (17.4 %) was significantly lower than that in patients with LC-EGVB (41.2 %). Patients with LC-EGVB exhibiting sarcopenia showed a high prevalence of portal vein thrombosis and rebleeding rate at 1 year. The rate of sarcopenia in the rebleeding group was significantly higher than that in the non-rebleeding group. Univariate and multivariate analyses showed that sarcopenia was an independent risk factor for rebleeding within 1 year in patients with LC-EGVB. Patients with LC-EGVB displayed a high prevalence of sarcopenia. Sarcopenia was observed to be an independent risk factor for rebleeding within 1 year.

Metabolic regulation in normal and leukemic stem cells.

Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) are crucial for ensuring hematopoietic homeostasis and driving leukemia progression, respectively. Recent research has revealed that metabolic adaptations significantly regulate the function and survival of these stem cells. In this review, we provide an overview of how metabolic pathways regulate oxidative and proteostatic stresses in HSCs during homeostasis and aging. Furthermore, we highlight targetable metabolic pathways and explore their interactions with epigenetics and the microenvironment in addressing the chemoresistance and immune evasion capacities of LSCs. The metabolic differences between HSCs and LSCs have profound implications for therapeutic strategies.

Cadonilimab with chemotherapy in HER2-negative gastric or gastroesophageal junction adenocarcinoma: the phase 1b/2 COMPASSION-04 trial.

Treatment with anti-programmed cell death protein 1 (PD-1) therapy and chemotherapy prolongs the survival of patients with unresectable advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The benefit from anti-PD-1 therapy is enriched in patients with programmed cell death 1 ligand 1 (PD-L1) combined positive score (CPS)-positive or CPS-high tumors compared with patients with PD-L1 CPS-negative or CPS-low tumors. In this phase 1b/2 study, we evaluated the efficacy and safety of cadonilimab, a bispecific antibody targeting PD-1 and cytotoxic T-lymphocyte antigen-4, plus chemotherapy as first-line treatment in patients with human epidermal growth factor receptor 2-negative unresectable advanced or metastatic gastric or GEJ adenocarcinoma. The primary endpoint was the recommended phase 2 dose (RP2D) for phase 1b and the objective response rate for phase 2. Secondary endpoints included disease control rate, duration of response, time to response, progression-free survival, overall survival (OS) and safety. The primary endpoint was met. No dose-limiting toxicities were observed during dose escalation in phase 1b; the recommended phase 2 dose was determined as 6 mg kg-1 every 2 weeks. The objective response rate was 52.1% (95% confidence interval (CI) = 41.6-62.5), consisting of complete and partial responses in 4.3% and 47.9% of patients, respectively. The median duration of response, progression-free survival and OS were 13.73 months (95% CI = 7.79-19.12), 8.18 months (95% CI = 6.67-10.48) and 17.48 months (95% CI = 12.35-26.55), respectively. The median OS in patients with a PD-L1 CPS ≥ 5 was 20.32 months (95% CI = 4.67-not estimable); in patients with a PD-L1 CPS < 1, the median OS reached 17.64 months (95% CI = 11.63-31.70). The most common treatment-related grade 3 or higher adverse events were decreased neutrophil count (19.1%), decreased platelet count (16.0%), anemia (12.8%) and decreased leukocyte count (8.5%). No new safety signal was identified. The current regimen showed promising clinical activity and manageable safety in patients with gastric or GEJ adenocarcinoma regardless of PD-L1 expression. Chinadrugtrials.org.cn registration: CTR20182027.

Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence.

It is well known that DNA damage can cause apoptosis. However, whether apoptosis and its metabolites contribute to DNA repair is largely unknown. In this study, we found that apoptosis-deficient Fasmut and Bim- /- mice show significantly elevated DNA damage and premature cellular senescence, along with a significantly reduced number of 16,000 g apoptotic vesicles (apoVs). Intravenous infusion of mesenchymal stromal cell (MSC)-derived 16,000 g apoVs rescued the DNA damage and premature senescence in Fasmut and Bim-/- mice. Moreover, a sublethal dose of radiation exposure caused more severe DNA damage, reduced survival rate, and loss of body weight in Fasmut mice than in wild-type mice, which can be recovered by the infusion of MSC-apoVs. Mechanistically, we showed that apoptosis can assemble multiple nuclear DNA repair enzymes, such as the full-length PARP1, into 16,000 g apoVs. These DNA repair components are directly transferred by 16,000 g apoVs to recipient cells, leading to the rescue of DNA damage and elimination of senescent cells. Finally, we showed that embryonic stem cell-derived 16,000 g apoVs have superior DNA repair capacity due to containing a high level of nuclear DNA repair enzymes to rescue lethal dose-irradiated mice. This study uncovers a previously unknown role of 16,000 g apoVs in safeguarding tissues from DNA damage and demonstrates a strategy for using stem cell-derived apoVs to ameliorate irradiation-induced DNA damage.

The "quadrant-sandwich" method in clockwise modular D2 lymph node dissection in laparoscopic total gastrectomy: a retrospective cohort study.

Background: For patients who need laparoscopic radical gastrectomy, lymph node dissection (LND) and optimization of surgical procedures are particularly important. This study introduces the "quadrant-sandwich" method in clockwise modular D2 LND and evaluates the advantages and safety of this method. Methods: The clinical data of 108 laparoscopic total gastrectomy patients admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2019 to January 2022 were retrospectively analyzed. Based on the different LND processes, 55 patients were allocated to the observation group, which underwent clockwise modular LND using the "quadrant-sandwich method", and 53 patients were allocated to the control group, which underwent traditional LND. The effectiveness and safety of the approach in terms of operation time, blood loss, lymph node yield, postoperative recovery and postoperative complications were observed in the two groups. Results: There was no statistical difference between the baseline data of the two groups. In relation to the surgery, the observation group had an operation time of 227.0±48.5 minutes, and intraoperative bleeding of 100.0 mL [inter-quartile range (IQR), 30.0-200.0 mL], while the control group had an operation time of 247±41.5 minutes, and intraoperative bleeding of 180.0 mL (IQR, 130.0-245.0 mL). There were statistically significant differences between the two groups in terms of the operation time and intraoperative bleeding (P=0.001, P=0.020). In relation to the LND, there were no statistically significant differences between the two groups in terms of the total number of lymph nodes in each division, and the number of positive lymph nodes. In relation to the post-operative results, there were no statistically significant differences between the two groups in terms of the post-operative pathological stage, first postoperative oral feeding, post-operative hospitalization time, and post-operative complications. Conclusions: Clockwise modular D2 LND using the "quadrant-sandwich method" is potentially safe and feasible in laparoscopic total gastrectomy. It not only ensures the thoroughness of the LND, but also ensures and efficient and fast surgical process, shortens the operation time, and reduces the amount of intraoperative bleeding.

Postoperative superior anastomotic leakage classification and treatment strategy for postoperative esophagogastric junction cancer.

Background: At present, anastomotic fistula cannot be avoided after adenocarcinoma of the esophagogastric junction (AEG). Once the anastomotic leakage occurs, the posterior mediastinum and the left thoracic cavity are often seriously infected, which further impairs respiratory and circulatory function, heightening the danger of the disease course. The aim of this study was to identify the characteristics of superior anastomotic leakage after surgery for AEG and recommend corresponding treatment strategies to improve the diagnosis and treatment of superior anastomotic leakage after surgery for AEG. Methods: The clinical data of 57 patients with superior anastomotic leakage after surgery for AEG in the Affiliated Cancer Hospital of Zhengzhou University from January 2017 to March 2019 were retrospectively analyzed, including 27 cases referred from external hospitals and 30 cases at the Affiliated Cancer Hospital of Zhengzhou University. According to the diameter and risk level of anastomotic leakage, the high anastomotic leakage is divided into types I, II, III, and IV. Results: Patients with preoperative comorbidities or those treated with the transabdominal approach or laparoscopic surgery often had type I and type II anastomotic leakage; meanwhile, patients with preoperative comorbidities and sacral perforation or those treated with a thoracic and abdominal approach or open surgery often had type III and IV fistula. The difference between types I-II and types III-IV was statistically significant (P<0.05). The mortality rate of patients with type III and type IV leakage was 14.8% within 90 days after operation, while no deaths occurred among patients with type I and type II leakage, and the difference in mortality between the two groups was statistically significant (P<0.05). Conclusions: After surgery for AEG, suitable treatment measures should be adopted according to the type of superior anastomotic leakage that occurs. Types III and IV superior anastomotic leakages are associated with higher mortality and require greater attention from surgeons.

Retrospective study of combined pelvic exenteration in the treatment of primary and recurrent pelvic malignant tumors.

Background: Pelvic malignant tumors often originate in the rectum, bladder, uterus, and other organs. In patients with locally advanced tumours in the presence of direct invasion of one or more organs, negative tumor resection margin (R0) resection can be very beneficial to patient survival if it can be performed. As a multidisciplinary and high-risk surgical method, the pelvic exenteration (PE) procedure has only been reported in a few medical centres internationally. We retrospectively analyzed the clinical data of patients who had undergone PE surgery in our hospital, in order to provide ideas for the best treatment of patients with pelvic malignant tumors. Methods: A retrospective analysis was conducted of 59 patients with pelvic malignant tumors admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to July 2021, all of whom received PE surgery. They were divided into two groups according to the location of the disease: the rectal cancer group (n=40) and the cervical cancer group (n=19). Statistical analysis was performed on the baseline and follow-up data of the two groups of patients. Results: (I) Patient baseline data. Compared to the rectal cancer group, more patients in the cervical cancer group received preoperative radiotherapy and chemotherapy (P=0.013), and had a lower R0 resection rate (P=0.037). Postoperative complications in patients with rectal cancer and cervical cancer were 27.5% and 47.3%, respectively. (II) Patient survival analysis after PE surgery. The 5-year survival rate was 36.6% in the rectal cancer group and 25.3% in the cervical cancer group. In the rectal cancer group, for the primary tumor, if there was no lymph node metastasis or no postoperative complications in the postoperative pathology, the patient had a good survival prognosis. Univariate analysis showed that recurrent rectal cancer, postoperative lymph node metastasis, postoperative complications, and microsatellite stability (MSS) were significant predictors of poor survival outcomes. Multivariate analysis showed that lymph node metastasis and postoperative complications were independent prognostic factors for patient survival. Conclusions: PE is a viable option for pelvic malignancies; aggressive radical resection of lesions and reduced postoperative complications can effectively improve patient outcomes.

Clinicopathological features and prognoses in younger and older patients with mismatch repair defects colorectal cancer: a retrospective comparative cohort study.

Background: Microsatellite instability-high (MSI-H) is an important biomarker for predicting the effects of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) patients. However, due to the low mutation rate of MSI-H/deficient mismatch repair (dMMR) in the overall population, some doctors are of the view that testing this indicator increases the burden on patients, and consequently some patients fail to receive the most beneficial treatment methods. In order to provide testing criteria for younger patients with a higher proportion of MSI-H, we designed this retrospective controlled study. Methods: A retrospective analysis was conducted of 1,901 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2017 to December 2019 and underwent CRC-related gene testing. For this analysis, 100 patients aged 40 or younger are defined as the young group, and 305 patients aged 71 and older but younger than 80 are defined as the elderly group. We included patients who met the following criteria: (I) underwent preoperative colonoscopy or gastroscopy and were diagnosed with CRC; (II) received perioperative adjuvant therapy; (III) underwent curative surgery for CRC. Each patient was followed up from the time of surgery until April 30, 2023, or death, with follow-up visits scheduled every 3 months for the first 2 years after surgery, and every 6 months thereafter. Clinical characteristics such as age, gender, body mass index (BMI), tumor depth (T), number of metastatic lymph nodes (N), distant metastasis (M), tumor, node, metastasis (TNM) stage, extent of surgical resection, tumor size, tumor location, differentiation grade, and carcinoembryonic antigen (CEA) levels were collected. The microsatellite instability (MSI) status was analyzed using fluorescence in situ hybridization (FISH). Results: In young CRC patients, the proportion of MSI-H is higher than in elderly CRC patients (33% vs. 10.16%, P<0.001). The proportion of poorly differentiated tumors is also higher in young CRC patients compared to elderly CRC patients (53% vs. 31.15%, P<0.001). However, there were no significant differences in clinical characteristics between young and elderly CRC patients. In terms of prognosis, survival analysis of the young group showed that MSI status [hazard ratio (HR) =0.26, 95% confidence interval (CI): 0.08-0.88, P=0.03], TNM staging (HR =3.84, 95% CI: 1.38-10.71, P=0.010) were associated with the prognosis of CRC patients. Conclusions: The mutation rate of MSI-H is higher in young CRC patients compared to older. Our study further confirms that MSI-H can serve as a favorable prognostic marker for CRC patients. This finding may provide valuable guidance for clinicians in terms of prognosis assessment and treatment selection. If feasible, we hope that MSI testing can be performed for all CRC patients to enable targeted testing, with particular attention to monitoring the MSI status in young patients. This will aid clinicians in selecting appropriate treatment strategies for these patients.

The long-term outcomes and prognostic factors about locally advanced right colon cancer: a retrospective cohort study.

Background: The first case of treatment with en bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) for locally advanced right-sided colon cancer (LARCC) invading the pancreas, duodenum, or other organs, was reported in 1953 by Van Prohaska. Right-sided colon cancers invading the pancreas and duodenum are rare. Surgery can be technically challenging, with unclear oncologic consequences, hence there are few reports on the clinical outcomes and factors associated with survival in this patient cohort. The need for neoadjuvant chemotherapy in patients with LARCC is controversial, and the long-term survival of these patients as well as the preferred treatment regimen needs to be explored. This paper reports our experience in right hemicolectomy with en bloc resection for LARCC. We conducted this study to analyze the clinical features and surgical outcomes of LARCC. Methods: A retrospective study was performed using a database of all patients who underwent RHCPD due to the tumour directly invading the duodenum and/or pancreas in a 19-year period [2003-2022]. We included patients whose primary tumor site was the right hemicolon and who had undergone a negative tumor resection margin (R0) resection. In addition, the adhesions between the colon and other organs in these patients were malignant adhesions. The primary outcome was the overall survival after surgery. The secondary endpoints of the study included 30-day postoperative mortality, postoperative complications, prognostic factors, and tumour genetics. All patients were followed up with postoperative imaging at an interval of 3 months for the first 3 years and at an interval of 6 months for the next 2 years, and annual follow-up thereafter. Survival was estimated using Kaplan-Meier analysis. Variables with P values <0.05 in univariate analysis were entered into multivariate Cox proportional risk regression to identify independent predictors of survival. Results: There were 47 patients (23 males and 24 females) who underwent en bloc resection for LARCC. The median age of the patients was 61 years (range, 38-80 years). R0 resection was achieved in all cases. The overall complication rate was 27.7% (n=13). Two patients died within 30 days of surgery. The overall survival was 80.9%, 63.5%, and 51.7% at 1, 3, and 5 years, respectively. Univariate survival analysis identified pancreatic invasion, regional lymph node positivity, more than two organs invaded, and no neoadjuvant treatment as predictors of poor survival (log-rank P<0.05). Multivariate analysis showed that regional lymph node positivity [95% confidence interval (CI): 1.145-7.736; P=0.025] and more than two organs invaded (95% CI: 1.321-26.981; P=0.020) were predictors of poor survival. Conclusions: Relatively optimistic clinical outcomes from en bloc resection were demonstrated for patients with LARCC. For LARCC patients, en bloc resection can be carefully considered.