Molecular and immunological characteristics of postoperative relapse in lymph node-positive esophageal squamous cell cancer.

BACKGROUND: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. METHODS: A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. RESULTS: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). CONCLUSION: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.

[Treatment of irreducible intertrochanteric femoral fracture in elderly by folding top technique combined with right-angle pliers prying and pulling under G-arm X-ray fluoroscopy].

Objective: To explore the effectiveness of irreducible intertrochanteric femoral fracture in the elderly by treating with folding top technique and right-angle pliers prying and pulling under G-arm X-ray fluoroscopy. Methods: The clinical data of 74 elderly patients with irreducible intertrochanteric femoral fracture admitted between February 2016 and December 2022 and met the selection criteria were retrospectively analyzed. Among them, 38 cases were treated with folding top technique combined with right-angle pliers prying and pulling under G-arm X-ray fluoroscopy and intramedullary nailing fixation (study group), and 36 cases were treated with limited open reduction combined with other reduction methods and intramedullary nailing fixation (control group). There was no significant difference in baseline data between the two groups, such as age, gender, cause of injury, affected side and classification of fractures, complicated medical diseases, and time from injury to operation ( P>0.05). The operation time, intraoperative blood loss, hospital stay, fracture reduction time, fracture healing time, and complications of the two groups were recorded and compared. The quality of fracture reduction was evaluated by Baumgaertner et al. and Chang et al. fracture reduction standards. Results: Patients in both groups were followed up 10-14 months, with an average of 12 months. The operation time and intraoperative blood loss in the study group were significantly less than those in the control group ( P<0.05), there was no significant difference in hospital stay between the two groups ( P>0.05). At 2 days after operation, according to the fracture reduction standards of Baumgaertner et al. and CHANG Shimin et al., the quality of fracture reduction in the study group was better than that in the control group, and the fracture reduction time in the study group was shorter than that in the control group, with significant differences ( P<0.05). After operation, the fractures of the two groups all healed, and there was no significant difference in healing time between the two groups ( P>0.05). During the follow-up, there was no complication such as incision infection, internal fixation failure, deep venous thrombosis of lower limbs, intramedullary nail breakage, spiral blade cutting, or hip varus in the two groups, except for 2 cases of coxa vara in the control group. Conclusion: For the irreducible intertrochanteric femoral fracture, using folding top technique combined with right-angle pliers prying and pulling under G-arm X-ray fluoroscopy can obviously shorten the operation time, reduce the intraoperative blood loss, and improve the quality of fracture reduction.

Characteristics of resistivity variation in deep granite and in-situ detection applications.

During the construction of deep vertical shafts, water inrush and flooding accidents are prone to occur, which seriously affect construction safety. Accurately determining the groundwater conditions is a prerequisite for effectively controlling water hazards and conducting risk management. In order to ensure the accuracy of the resistivity method in deep vertical well water exploration construction, a combination of indoor rock physics, mechanical testing, and on-site engineering measurements was used to analyze the influencing factors of granite resistivity. The corresponding relationship between resistivity and formation integrity was revealed, and water exploration experiments were conducted in the working face of deep underground mines. The results show that: (1) Rock resistivity is influenced by metallic minerals, saturation, temperature, ion content of fracture water, and joints. Regarding deep subsurface detection issues, the main factors affecting the detection results are water content and rock integrity. (2) During the loading process, rock resistivity exhibits significant stage response characteristics, which are closely related to rock integrity and damage accumulation. (3) A degradation model for aquifer zoning based on resistivity benchmark line was established. When the formation resistivity is higher than the benchmark line, it indicates a well-integrated formation with low water content. (4) Resistivity cloud maps and zoning degradation models can be used to visually determine and evaluate the occurrence status of formations and the effectiveness of grouting.

In Situ Nanofiber Formation Blocks AXL and GAS6 Binding to Suppress Ovarian Cancer Development.

Anexelekto (AXL) is an attractive molecular target for ovarian cancer therapy because of its important role in ovarian cancer initiation and progression. To date, several AXL inhibitors have entered clinical trials for the treatment of ovarian cancer. However, the disadvantages of low AXL affinity and severe off-target toxicity of these inhibitors limit their further clinical applications. Herein, by rational design of a nonapeptide derivative Nap-Phe-Phe-Glu-Ile-Arg-Leu-Arg-Phe-Lys (Nap-IR), a strategy of in situ nanofiber formation is proposed to suppress ovarian cancer growth. After administration, Nap-IR specifically targets overexpressed AXL on ovarian cancer cell membranes and undergoes a receptor-instructed nanoparticle-to-nanofiber transition. In vivo and in vitro experiments demonstrate that in situ formed Nap-IR nanofibers efficiently induce apoptosis of ovarian cancer cells by blocking AXL activation and disrupting subsequent downstream signaling events. Remarkably, Nap-IR can synergistically enhance the anticancer effect of cisplatin against HO8910 ovarian tumors. It is anticipated that the Nap-IR can be applied in clinical ovarian cancer therapy in the near future.

Deciphering the heterogeneity of neutrophil cells within circulation and the lung cancer microenvironment pre- and post-operation.

Neutrophils play a crucial role in the immune system within tumor microenvironment. At present, numerous studies have explored the changes of neutrophils' automatic killing effect and cellular communication with other immune cells under pathological conditions through single-cell sequencing. However, there remains a lack of definite conclusion about the identification criteria of neutrophil subgroups. Here, we collected tumor and para-carcinoma tissues, pre- and postoperative blood from patients with non-small cell lung cancer (NSCLC), and performed single-cell RNA (scRNA) sequencing to evaluate the distribution of neutrophil subgroups. We have developed a computational method of over expression rate (OER) to evaluate the specificity of neutrophil subgroups, in order to target gene panels with potential clinical application value. In addition, OER was used to evaluate specificity of neutrophil subsets in healthy people and patients with various diseases to further validate the feasibility of this evaluation system. As a result, we found the specificity of Neu_ c1_ IL1B and Neu_ c2_ cxcr4 (low) in postoperative blood has increased, while that of IL-7R + neutrophils has decreased, indicating that these groups of cells possibly differentiated or migrated to other subgroups in the state of lung cancer. In addition, seven gene panels (Neu_c3_CST7, RSAD2_Neu, S100A2/Pabpc1_Neu, ISG15/Ifit3_Neu, CD74_Neu, PTGS2/Actg1_Neu, SPP1_Neu) were high specific in all the four NSCLC-associated samples, meaning that changes in the percentage of these cell populations would have a high degree of confidence in assessing changes of disease status. In conclusion, combined consideration of the distribution characteristics of neutrophil subgroups could help evaluate the diagnosis and prognosis of NSCLC.

Association between the surgical approach and prognosis of spontaneous supratentorial deep intracerebral hemorrhage.

The association between surgical approach and prognosis in patients with spontaneous supratentorial deep intracerebral hemorrhage is unclear. We aimed to explore the association between surgical approach and prognosis in these patients. A retrospective cohort of 311 patients from 3 centers who were treated with surgery 24 h after ictus was recruited. The surgical procedure involved removing the intracerebral hematoma using an aspirator through either the cortical approach or Sylvian fissure approach, assisted by an endoscope or microscope. The primary outcome was the one-year modified Rankin scale (mRS) score. The association between the surgical approach and the one-year mRS score was explored by using ordinal logistic regression and binary logistic regression. Baseline characteristics were balanced by propensity score matching and inverse propensity score weighting. In the adjusted analysis, compared with the cortex approach group, the Sylvian fissure approach group had better one-year mRS scores when analyzed as an ordinal variable (3.00 [2.00-4.00] vs. 4.00 [3.00-5.00]; adjusted odds ratio, 3.15; 95% CI, 1.78-5.58; p < 0.001) and a dichotomous variable (74.14% vs. 49.01%; adjusted odds ratio, 6.61; 95% CI, 2.75-15.88; p < 0.001). Surgical approach was not significantly associated with rebleeding (p = 0.88) or three-month mortality (p = 0.81). In univariate analysis after propensity score matching, there were significant differences in one-year mRS score between the two groups (p < 0.001), and there were no significant differences in rebleeding (Fisher's exact test, p > 0.999) or three-month mortality (Fisher's exact test, p > 0.999). Inverse probability weighted regression analysis showed better one-year mRS scores when analyzed as an ordinal variable (adjusted odds ratio, 3.03; 95% CI, 2.17-4.17; p < 0.001) and a dichotomous variable (adjusted odds ratio, 3.11; 95% CI, 2.16-4.77; p < 0.001) in the Sylvian fissure approach group; the surgical approach was not significantly associated with rebleeding (p = 0.50) or three-month mortality (p = 0.60). In the surgical treatment of patients with spontaneous supratentorial deep intracerebral hemorrhage, the Sylvian fissure approach may lead to a better functional outcome compared with the cortex approach. Future prospective studies are warranted to confirm this finding.

Endolysosomal trafficking controls yolk granule biogenesis in vitellogenic Drosophila oocytes.

Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly from studies in yeast and cultured mammalian cells, one challenge is to systematically evaluate the findings from these cell-based studies in multicellular organisms under physiological settings. One potentially valuable in vivo system to address this challenge is the vitellogenic oocyte in Drosophila, which undergoes extensive endocytosis by Yolkless (Yl), a low-density lipoprotein receptor (LDLR), to uptake extracellular lipoproteins into oocytes and package them into a specialized lysosome, the yolk granule, for storage and usage during later development. However, by now there is still a lack of sufficient understanding on the molecular and cellular processes that control yolk granule biogenesis. Here, by creating genome-tagging lines for Yl receptor and analyzing its distribution in vitellogenic oocytes, we observed a close association of different endosomal structures with distinct phosphoinositides and actin cytoskeleton dynamics. We further showed that Rab5 and Rab11, but surprisingly not Rab4 and Rab7, are essential for yolk granules biogenesis. Instead, we uncovered evidence for a potential role of Rab7 in actin regulation and observed a notable overlap of Rab4 and Rab7, two Rab GTPases that have long been proposed to have distinct spatial distribution and functional roles during endolysosomal trafficking. Through a small-scale RNA interference (RNAi) screen on a set of reported Rab5 effectors, we showed that yolk granule biogenesis largely follows the canonical endolysosomal trafficking and maturation processes. Further, the data suggest that the RAVE/V-ATPase complexes function upstream of or in parallel with Rab7, and are involved in earlier stages of endosomal trafficking events. Together, our study provides s novel insights into endolysosomal pathways and establishes vitellogenic oocyte in Drosophila as an excellent in vivo model for dissecting the highly complex membrane trafficking events in metazoan.

PTCH1 mutation as a potential predictive biomarker for immune checkpoint inhibitors in gastrointestinal cancer.

Immune checkpoint inhibitors (ICIs) have become prominent therapies for gastrointestinal cancer (GC). However, it is urgent to screen patients who can benefit from ICIs. Protein patched homolog 1 (PTCH1) is a frequently altered gene in GC. We attempt to explore the association between PTCH1 mutation and immunotherapy efficacy. The Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 236) with GC (esophageal, gastric and colorectal cancers) patients receiving ICIs was used for discovery and the Peking University Cancer Hospital (PUCH) GC cohort (n = 92) was used for validation. Overall survival (OS) and tumor mutational burden (TMB) of the PTCH1 mutant-type (PTCH1-MUT) and PTCH1 wild-type (PTCH1-WT) groups were compared. Furthermore, GC data were collected from The Cancer Genome Atlas to assess the potential mechanisms. In the MSKCC cohort, PTCH1-MUT group showed significantly better OS (P = 0.017) and higher TMB. Multivariate analysis showed that PTCH1 mutation was associated with better OS. In the PUCH cohort, PTCH1-MUT group showed significantly longer OS (P = 0.036) and progression-free survival, and higher durable clinical benefit and TMB. Immune cell infiltration analysis revealed that PTCH1-MUT group had significantly higher distributions of CD8 T cells, CD4 T cells, NK cells, mast cells and M1 cells. The PTCH1-MUT group showed significantly higher expression of most immune-related genes. Gene set enrichment analysis showed that the PTCH1-MUT group had enriched INF-γ response, INF-α response, glycolysis and reactive oxygen species pathway gene sets. PTCH1 mutation may represent a potential biomarker for predicting ICIs response in GC. Nevertheless, prospective cohort studies should be performed to further validate our results.

MoNP-doped Defective Carbon Fibers with Bark-like Nanosurface as Effective Bifunctional Electrocatalysts for Zn-air Batteries.

The flexible air electrode with high oxygen electrocatalytic performance and outstanding stability under various deformations plays a vital role in high-performance flexible Zn-air batteries (ZABs). Herein, a self-supported Mo, N, and P co-doped carbon cloth (CC) denoted as MoNP@CC with bark-like surface structure is fabricated by a facile two-step approach via a one-pot method and pyrolysis. The surface of the electrode shows a nanoscale "rift valley" and uniformly distributed active sites. Taking advantage of the nano-surface as well as transition metal and heteroatom doping, the self-supported electrocatalysis air electrode exhibits considerable oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) performance in terms of low overpotential (388 mV at 10 mA cm-2 ) for OER and a much positive potential (0.74 V) at 1.0 mA cm-2 for ORR. Furthermore, MoNP@CC is further used for the flexible ZAB to demonstrate its practical application. The MoNP@CC-based ZAB displays a good cycling performance for 2800 min and an open-circuit voltage of 1.44 V. This work provides a new approach to the construction of a high-performance, self-supported electrocatalysis electrode used for a flexible energy storage device.

RPTOR mutation: a novel predictor of efficacious immunotherapy in melanoma.

Identifying biomarkers to evaluate the therapeutic effect of immune checkpoint inhibitors (ICIs) is crucial. Regulatory Associated Protein of MTOR Complex 1 (RPTOR), one of the genes in the mTOR pathway, plays a role in regulating tumor progression. However, the connection between RPTOR mutation and the efficacy of ICIs in melanoma remains unclear. The data of ICIs-treated melanoma patients in discovery (n = 384) and validation (n = 320) cohorts were obtained from cBioPortal databases. The genomic data in the two cohorts was used to investigate the connection between RPTOR mutation and immunotherapy efficacy. The underlying mechanisms were explored based on data from the The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) cohort. Compared to melanoma patients with RPTOR wildtype (RPTOR-WT), RPTOR-mutation (RPTOR-Mut) patients achieved prolonged overall survival (OS) in both discovery cohort (median OS of 49.3 months vs. 21.7 months; HR = 0.41, 95% CI: 0.18-0.92; P = 0.026) and validation cohorts (not reached vs. 42.0 months; HR = 0.34, 95% CI: 0.11-1.06; P = 0.049). RPTOR-Mut melanoma patients exhibited a higher objective response rate (ORR) than RPTOR-WT patients in the discovery cohort (55.0% vs. 29.0%, P = 0.022). RPTOR-Mut patients exhibited higher TMB than RPTOR-WT patients in both discovery and validation cohorts (P < 0.001). RPTOR-Mut melanoma patients had an increased number of DNA damage response (DDR) mutations in TCGA-SKCM cohort. Immune cell infiltration analysis suggested that activated CD4 memory T cells were more enriched in RPTOR-Mut tumors. RPTOR-Mut melanoma patients had higher expression levels of immune-related genes than the RPTOR-WT patients. Our results suggest that RPTOR mutation could serve as a predictor of effective immunotherapy for melanoma.

SCAR: Single-cell and Spatially-resolved Cancer Resources.

Advances in sequencing and imaging technologies offer a unique opportunity to unravel cell heterogeneity and develop new immunotherapy strategies for cancer research. There is an urgent need for a resource that effectively integrates a vast amount of transcriptomic profiling data to comprehensively explore cancer tissue heterogeneity and the tumor microenvironment. In this context, we developed the Single-cell and Spatially-resolved Cancer Resources (SCAR) database, a combined tumor spatial and single-cell transcriptomic platform, which is freely accessible at http://8.142.154.29/SCAR2023 or http://scaratlas.com. SCAR contains spatial transcriptomic data from 21 tumor tissues and single-cell transcriptomic data from 11 301 352 cells encompassing 395 cancer subtypes and covering a wide variety of tissues, organoids, and cell lines. This resource offers diverse functional modules to address key cancer research questions at multiple levels, including the screening of tumor cell types, metabolic features, cell communication and gene expression patterns within the tumor microenvironment. Moreover, SCAR enables the analysis of biomarker expression patterns and cell developmental trajectories. SCAR also provides a comprehensive analysis of multi-dimensional datasets based on 34 state-of-the-art omics techniques, serving as an essential tool for in-depth mining and understanding of cell heterogeneity and spatial location. The implications of this resource extend to both cancer biology research and cancer immunotherapy development.

SCAN: Spatiotemporal Cloud Atlas for Neural cells.

The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge challenge. Here, we manually collected and comprehensively analyzed high-quality scRNA-seq and ST data from the nervous system, covering 10 679 684 cells. In addition, multi-omic datasets from more than 900 species were included for extensive data mining from an evolutionary perspective. Furthermore, over 100 neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, Down syndrome) were systematically analyzed for high-throughput screening of putative biomarkers. Differential expression patterns across developmental time points, cell types and ST spots were discerned and subsequently subjected to extensive interpretation. To provide researchers with efficient data exploration, we created a new database with interactive interfaces and integrated functions called the Spatiotemporal Cloud Atlas for Neural cells (SCAN), freely accessible at http://47.98.139.124:8799 or http://scanatlas.net. SCAN will benefit the neuroscience research community to better exploit the spatiotemporal atlas of the neural system and promote the development of diagnostic strategies for various neurological disorders.

Immunoneoadjuvant therapy with immune checkpoint inhibitors of gastric cancer: an emerging exemplification : Immunoneoadjuvant therapy of gastric cancer.

Advances in immune checkpoint inhibitors (ICIs) have enabled more effective treatment for individuals with various types of solid tumors. Given the improved survival benefit and acceptable safety profile of ICIs in advanced gastric cancer, there is plenty of interest in the use of ICIs in the neoadjuvant setting with curative intent. Theoretically, immunoneoadjuvant with ICIs could boost the levels of endogenous tumor antigen present in the tumor to enhance T-cell priming and further enhance systemic immunity. This systemic immune response may improve the detection and elimination of the disseminated micrometastatic tumors beyond the resected tumor, which are sources of postsurgical relapse. Numerous clinical studies have begun to explore the application of ICIs in neoadjuvant treatment of gastric cancer. This article reviews the progress in the use of ICI monotherapy and in combination with alternative therapies for the treatment of gastric cancer to aid in the development of gastric cancer immunoneoadjuvant therapy and improve the overall therapeutic benefit.

Artificial dermis combined with skin grafting for the treatment of hand skin and soft tissue defects and exposure of bone and tendon.

BACKGROUND: The recovery time of hand wounds is long, which can easily result in chronic and refractory wounds, making the wounds unable to be properly repaired. The treatment cycle is long, the cost is high, and it is prone to recurrence and disability. Double layer artificial dermis combined with autologous skin transplantation has been used to repair hypertrophic scars, deep burn wounds, exposed bone and tendon wounds, and post tumor wounds. AIM: To investigate the therapeutic efficacy of autologous skin graft transplantation in conjunction with double-layer artificial dermis in treating finger skin wounds that are chronically refractory and soft tissue defects that expose bone and tendon. METHODS: Sixty-eight chronic refractory patients with finger skin and soft tissue defects accompanied by bone and tendon exposure who were admitted from July 2021 to June 2022 were included in this study. The observation group was treated with double layer artificial dermis combined with autologous skin graft transplantation (n = 49), while the control group was treated with pedicle skin flap transplantation (n = 17). The treatment status of the two groups of patients was compared, including the time between surgeries and hospital stay. The survival rate of skin grafts/flaps and postoperative wound infections were evaluated using the Vancouver Scar Scale (VSS) for scar scoring at 6 mo after surgery, as well as the sensory injury grading method and two-point resolution test to assess the recovery of skin sensation at 6 mo. The satisfaction of the two groups of patients was also compared. RESULTS: Wound healing time in the observation group was significantly longer than that in the control group (P < 0.05, 27.92 ± 3.25 d vs 19.68 ± 6.91 d); there was no significant difference in the survival rate of skin grafts/flaps between the two patient groups (P > 0.05, 95.1 ± 5.0 vs 96.3 ± 5.6). The interval between two surgeries (20.0 ± 4.3 d) and hospital stay (21.0 ± 10.1 d) in the observation group were both significantly shorter than those in the control group (27.5 ± 9.3 d) and (28.4 ± 17.7 d), respectively (P < 0.05). In comparison to postoperative infection (23.5%) and subcutaneous hematoma (11.8%) in the control group, these were considerably lower at (10.2%) and (6.1%) in the observation group. When comparing the two patient groups at six months post-surgery, the excellent and good rate of sensory recovery (91.8%) was significantly higher in the observation group than in the control group (76.5%) (P < 0.05). There was also no statistically significant difference in two point resolution (P > 0.05). The VSS score in the observation group (2.91 ± 1.36) was significantly lower than that in the control group (5.96 ± 1.51), and group satisfaction was significantly higher (P < 0.05, 90.1 ± 6.3 vs 76.3 ± 5.2). CONCLUSION: The combination of artificial dermis and autologous skin grafting for the treatment of hand tendon exposure wounds has a satisfactory therapeutic effect. It is a safe, effective, and easy to operate treatment method, which is worthy of clinical promotion.

Risk factors for sternal wound infection after open-heart operations: A systematic review and meta-analysis.

We aimed to quantitatively and systematically elucidate the rationality of the examined variables as independent risk factors for sternal wound infection. We searched databases to screen studies, ascertained the variables to be analysed, extracted the data and applied meta-analysis to each qualified variable. Odds ratios and mean differences were considered to be the effect sizes for binary and continuous variables, respectively. A random-effects model was used for these procedures. The source of heterogeneity was evaluated using a meta-regression. Publication bias was tested by funnel plot and Egger's test, the significant results of which were then calculated using trim and fill analysis. We used a sensitivity analysis and bubble chart to describe their robustness. After screening all variables in the eligible literature, we excluded 55 because only one or no research found them significant after multivariate analysis, leaving 33 variables for synthesis. Two binary variables (age over 65 years, NYHA class >2) and a continuous variable (preoperative stay) were not significant after the meta-analysis. The most robust independent risk factors in our study were diabetes mellitus, obesity, use of bilateral internal thoracic arteries, chronic obstructive pulmonary disease, prolonged surgery time, prolonged ventilation and critical preoperative state, followed by congestive heart failure, atrial fibrillation, renal insufficiency, stroke, peripheral vascular disease and use of an intra-aortic balloon pump. Relatively low-risk factors were emergent/urgent surgery, smoking, myocardial infarction, combined surgery and coronary artery bypass grafting. Sternal wound infection after open-heart surgery is a multifactorial disease. The detected risk factors significantly affected the wound healing process, but some were different in strength. Anything that affects wound healing and antibacterial ability, such as lack of oxygen, local haemodynamic disorders, malnutrition condition and compromised immune system will increase the risk, and this reminds us of comprehensive treatment during the perioperative period.

Gastrointestinal signet ring cell malignancy: current advancement and future prospects.

Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation.

The impacts of ship emissions on ozone in eastern China.

Tropospheric ozone (O3), which is one of the main pollutants impeding air quality compliance, has received considerable attention in China. As maritime transportation continues to expand, the effect of ship emissions on air quality is becoming increasingly important. In this study, the Weather Research and Forecast model (WRF), the Community Multiscale Air Quality model (CMAQ), and the integrated process rate (IPR) module provided in the CMAQ are applied to evaluate the impacts of ship emissions on O3 concentration at a national scale in China, including the spatiotemporal characteristics and influencing pathways. Ship emissions can increase or decrease O3 concentrations, with varying effects in different seasons and regions. In the winter, spring, and fall, ship emissions were predicted to decrease O3 concentrations in most areas, whereas in the summer, they increase the O3 concentration, even in regions far away from the coastline, thus adversely affecting the Yangtze River Delta (YRD) and Pearl River Delta (YRD). Additionally, owing to differences in the emissions of volatile organic compounds and nitrogen oxides, the northern and southern regions of the YRD respond differently to ship emissions. Additionally, the influence of ship emissions on the diurnal variation of O3 in the summer was investigated, where significant differences were indicated between cities. The IPR was used to investigate the individual processes contributing to changes in the O3 concentration caused by ship emissions. The transport process appears to be the primary contributor to O3 production, whereas chemistry and dry deposition played key roles in O3 loss. This study provides an in-depth insight into the impacts of ship emissions on O3 in China, which can facilitate the formulation of corresponding environmental policies.

The role of mechano-regulated YAP/TAZ in erectile dysfunction.

Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.

Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics.

As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms.

Risk factors associated with tendon adhesions after hand tendon repair.

Background: Tendon adhesions after hand tendon repair are one of the most difficult complications of hand surgery and can cause severe disability. This study aimed to assess the risk factors associated with tendon adhesions after hand tendon repair to provide a theoretical foundation for the early prevention of tendon adhesions in patients with tendon injuries. Moreover, this study intends to increase doctors' awareness of the issue and serves as a reference for developing new prevention and treatment strategies. Methods: We retrospectively analyzed 1,031 hand trauma cases that underwent repair after finger tendon injury in our department between June 2009 and June 2019. Tendon adhesions, tendon injury zones, and other relevant information were collected, summarized, and analyzed. The significance of data was determined using a t-test or Pearson's chi-square test, and odds ratios (OR) were calculated using logistic regression tests to describe factors associated with post-tendon repair adhesions. Results: A total of 1,031 patients were enrolled in this study. There were 817 males and 214 females with an average age of 34.98 (2-82) years. The injured side included 530 left and 501 right hands. Postoperative finger tendon adhesions occurred in 118 cases (11.45%), including 98 males and 20 females, 57 left and 61 right hands. The risk factors for the total sample in the descending order were degloving injury, no functional exercise, zone II flexor tendon injury, time from injury to surgery >12 h, combined vascular injury, and multiple tendon injuries. The flexor tendon sample shared the same risk factors as the total sample. Risk factors for the extensor tendon sample were degloving injury, no functional exercise. Conclusions: Clinicians should pay close attention to patients with tendon trauma in hand having the following risk factors: degloving injury, zone II flexor tendon injury, lack of functional exercise, time from injury to surgery >12 h, combined vascular injury, and multiple tendon injuries. Due to the high risk of post-repair adhesions in patients with the conditions mentioned above, individualized treatment measures should be designed for the risk factors, and postoperative functional exercise of the hand is required.