CBLC promotes the development of colorectal cancer by promoting ABI1 degradation to activate the ERK signaling pathway.

CBLC (CBL proto-oncogene C) is an E3 ubiquitin protein ligase that plays a key role in cancers. However, the function and mechanism of CBLC in colorectal cancer (CRC) has not been fully elucidated. The aim of this study was to investigate the function of CBLC in CRC and its underlying molecular mechanism. High CBLC levels were certified in tumor tissues of CRC patients, and its expression was positively associated with TNM stage. Next, we explored the role of CBLC in CRC using gain or loss of function. For biological function analysis, CCK-8 cell proliferation, colony formation, flow cytometry, scratch, and transwell assays collectively suggested that CBLC overexpression promoted cell proliferation, cell cycle progression, migration and invasion. As observed, CBLC knockdown exhibited exactly opposite effects, resulting in impaired tumorigenicity in vitro. Xenograft studies displayed that CBLC overexpression accelerated tumor growth and promoted tumor metastasis to the lung, while the inhibitory effects of CBLC knockdown on tumorigenicity and metastasis ability of CRC cells was also confirmed. Furthermore, the molecular mechanism of CBLC in CRC was explored. CBLC induced the activation of ERK signaling pathway, further leading to its pro-tumor role. Notably, CBLC decreased ABI1 (Abelson interactor protein-1, a candidate tumor suppressor) protein levels through its ubiquitin ligase activity, while ABI1 upregulation abolished the effects of CBLC on the tumorigenesis of CRC. Taken together, these results demonstrate that CBLC acts as a tumor promoter in CRC through triggering the ubiquitination and degradation of ABI1 and activating the ERK signaling pathway. CBLC may be a potential novel target for CRC.

Effect of topical steroid on soft tissue swelling following anterior cervical discectomy and fusion.

Background: Anterior cervical discectomy and fusion is the most commonly used surgical approach for treating cervical spine conditions, but it can often lead to postoperative swallowing difficulties. To retrospectively assess the effects of topical triamcinolone acetonide in the anterior cervical surgery on swallowing function. Methods: In this study, a retrospective design was used to select patients aged 18 years and older who were diagnosed with cervical spondylosis and required anterior cervical discectomy and fusion. Among them, the patients in the experimental group used triamcinolone acetonide topically in front of the plate during surgery, and the control group was the patients who did not use triamcinolone acetonide. The sex, age, operation time, operation segment, and preoperative soft tissue area were compared between the two groups. Results: There were no significant differences in gender, age, operation time, and segment between the two groups. For the preoperative soft tissue area, triamcinolone acetonide was significantly lower than in the control group (P < 0.05). Conclusion: The retrospective results of this study support that topical triamcinolone acetonide as a treatment in anterior cervical surgery can significantly reduce soft tissue swelling, and no effect was found on the operation time, postoperative blood loss, and segment. These findings provide an important basis for clinical care teams to make treatment decisions and confirm the effectiveness of triamcinolone acetonide in improving swallowing function. However, there was a possibility of information collection and selection bias due to the limitations of retrospective studies. To confirm and further advance the use of this treatment, more rigorous prospective randomized controlled trials are recommended to validate these preliminary results.

The small screw-apex distance is potentially associated with femoral head osteonecrosis in adults with femoral neck fractures treated by closed reduction and percutaneous 3 parallel cannulated screws.

OBJECTIVE: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH. PATIENTS AND METHODS: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated. RESULTS: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively). CONCLUSIONS: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.

Chemotherapy-induced pneumatosis intestinalis followed by hepatic portal venous gas. A case report.

Pneumatosis intestinalis (PI) is a rare disease, and there are many theories about its pathogenesis. Hepatic portal venous gas (HPVG), is thought to occur secondary to intramural intestinal gas emboli migrating through the portal venous system via the mesenteric veins. PI accompanied by HPVG is usually a sign of bowel ischaemia and is associated with a high mortality rate. We report here, a patient with liver metastases from colorectal cancer who developed PI followed by HPVG after treatment with 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6). Timely attention and management of gastrointestinal symptoms following chemotherapy are essential in the treatment of this type of patient.

The efficacy and safety of tranexamic acid in transforaminal lumbar interbody fusion: a systematic review and meta-analysis.

Purpose: This meta-analysis aimed to assess the efficacy and safety of tranexamic acid (TXA) in transforaminal lumbar interbody fusion (TLIF), focusing on its impact on intraoperative blood loss and related outcomes. Methods: The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, Medline, and Cochrane Library databases to identify all literature related with TXA and TLIF. Finally, five trials ultimately meeting the inclusion criteria. Continuous variables were analyzed using mean difference and categorical variables were analyzed using Peto odds ratio, via random effects models. Results: The meta-analysis revealed a significant reduction in intraoperative blood loss associated with TXA use during TLIF, as confirmed by the RCTs. However, the impact of TXA on other outcomes, such as postoperative drainage volume, total blood loss, and length of hospital stay, remains inconclusive due to limited data. No severe complications related to TXA use were reported, providing preliminary evidence of its safety in TLIF. Conclusion: TXA appears to effectively reduce intraoperative blood loss in TLIF, based on the available RCT evidence. However, further research is needed to provide a comprehensive assessment of TXA's overall impact on various outcomes in this context. This meta-analysis underscores the importance of ongoing investigation to establish the full potential and safety profile of TXA in TLIF procedures.

Higher anthocyanin intake is associated with a lower risk of non-alcoholic fatty liver disease in the United States adult population.

Background: Flavonoids are a class of plant chemicals known to have health-promoting properties, including six subclasses. Anthocyanin is one of the subclasses that have anti-inflammatory and antioxidant activities. However, the relationship between flavonoid subclass intake and the risk of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis has not been verified in representative samples of the United States. Methods: This is a cross-sectional study based on the data from the National Health and Nutrition Examination Survey (NHANES) and the Food and Nutrient Database for Dietary Studies (FNDDS) in 2017-2018. The intake of flavonoid subclasses of the participants was obtained from two 24 h dietary recalls. The NAFLD and liver fibrosis were defined based on the international consensus criteria. The relationship between flavonoid subclass intake and NAFLD and liver fibrosis was evaluated using a multivariate logistic regression model corrected for multiple confounding factors. Subgroup analysis, trend tests, interaction tests and restricted cubic spline were carried out to further explore this relationship. In addition, we also explored the relationship between anthocyanin and liver serum biomarkers, dietary total energy intake and healthy eating index (HEI)-2015 scores. Results: A total of 2,288 participants were included in the analysis. The intake of anthocyanin was significantly negatively associated with the risk of NAFLD, but not other flavonoid subclasses. A higher anthocyanin intake was significantly associated with a lower risk of NAFLD (quartile 4, OR 0.470, 95% CI 0.275-0.803). The results of subgroup analysis showed that the protective effect of dietary anthocyanin intake on NAFLD was more pronounced in participants of non-Hispanic whites, with hypertension and without diabetes (P for interaction <0.05). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), dietary total energy intake was significantly negatively correlated with dietary anthocyanin intake. We did not find any protective effect of flavonoid subclass intake on liver fibrosis. Conclusion: Anthocyanin, but not other flavonoid subclasses, can significantly reduce the risk of NAFLD. The protective effect was more pronounced in non-Hispanic whites, participants without diabetes and those with hypertension. Our study provides new evidence that anthocyanin intake has a reverse significant association with the risk for NAFLD.

Effects of tourniquet on surgical site wound infection and pain after total knee arthroplasty: A meta-analysis.

The application of a tourniquet (TNQ) for haemostasis in total knee arthroplasty (TKA) is controversial and lacking systematic evaluation. This meta-analysis assessed relevant international data to quantitatively evaluate the implications of using TNQ in TKA, further guide clinical diagnosis and treatment, and improve postoperative outcomes. A comprehensive computerised search of PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, VIP, and Wanfang databases was conducted to retrieve randomised controlled trials on the application of TNQ in TKA published from database inception to August 2023. The included data, ultimately comprising 1482 patients in 16 studies, were collated and subjected to meta-analysis using Stata 17.0 software. The results showed that the use of TNQ during TKA led to significantly higher rates of postoperative surgical site wound infection (3.96% vs. 1.79%, odds ratio: 2.15, 95% confidence intervals [CIs]: 1.11-4.16, p = 0.023) and wound pain scores on the first (standardised mean difference [SMD]: 0.65, 95% CI: 0.35-0.94, p < 0.001), second (SMD: 0.66, 95% CI: 0.01-1.31, p = 0.045), and third (SMD: 0.68, 95% CI: 0.31-1.05, pP < 0.001) day after the procedure. In conclusion, the application of TNQ in TKA increases the risk of postoperative surgical site wound infection and worsens short-term postoperative wound pain; therefore, TNQ should be used sparingly during TKA, or its use should be decided in conjunction with the relevant clinical indications and the surgeon's experience.

Effect of vehicle external acceleration signal light on pedestrian-vehicle interaction.

The number of casualties resulting from collisions between pedestrians and motor vehicles continues to rise. A significant factor is the misunderstanding of vehicle behavior intentions by pedestrians. This is especially true with the continuous development of vehicle automation technology, which has reduced direct interaction between drivers and the outside world. Therefore, accurate communication of vehicle behavior intentions is becoming increasingly important. The purpose of this study is to investigate the impact of external vehicle acceleration signal light on the interaction experience between pedestrians and vehicles. The differences between the use and nonuse of acceleration signal light are compared through controlled test track experiments in real scenarios and in videos.The results show that acceleration signal light help pedestrians understand vehicle behavior intentions more quickly and make safer crossing decisions as well as improving their perception of safety when crossing the street and their trust in vehicle behavior.

Rhein alleviates advanced glycation end products (AGEs)-induced inflammatory injury of diabetic cardiomyopathy in vitro and in vivo models.

In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE2, iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKß and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKß activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy.

A virtual biopsy study of microsatellite instability in gastric cancer based on deep learning radiomics.

OBJECTIVES: This study aims to develop and validate a virtual biopsy model to predict microsatellite instability (MSI) status in preoperative gastric cancer (GC) patients based on clinical information and the radiomics of deep learning algorithms. METHODS: A total of 223 GC patients with MSI status detected by postoperative immunohistochemical staining (IHC) were retrospectively recruited and randomly assigned to the training (n = 167) and testing (n = 56) sets in a 3:1 ratio. In the training set, 982 high-throughput radiomic features were extracted from preoperative abdominal dynamic contrast-enhanced CT (CECT) and screened. According to the deep learning multilayer perceptron (MLP), 15 optimal features were optimized to establish the radiomic feature score (Rad-score), and LASSO regression was used to screen out clinically independent predictors. Based on logistic regression, the Rad-score and clinically independent predictors were integrated to build the clinical radiomics model and visualized as a nomogram and independently verified in the testing set. The performance and clinical applicability of hybrid model in identifying MSI status were evaluated by the area under the receiver operating characteristic (AUC) curve, calibration curve, and decision curve (DCA). RESULTS: The AUCs of the clinical image model in training set and testing set were 0.883 [95% CI: 0.822-0.945] and 0.802 [95% CI: 0.666-0.937], respectively. This hybrid model showed good consistency in the calibration curve and clinical applicability in the DCA curve, respectively. CONCLUSIONS: Using preoperative imaging and clinical information, we developed a deep-learning-based radiomics model for the non-invasive evaluation of MSI in GC patients. This model maybe can potentially support clinical treatment decision making for GC patients.

Comparative study on the inhibiting effect of dissolvable tiny-foam extinguishing agent and chlorine salts on coal spontaneous combustion.

Coal spontaneous combustion (CSC) is a global disaster and detrimental to the ecological environment. This study aims to better apply environmentally friendly dissolvable tiny-foam extinguisher (DTE) to CSC and look further into the inhibition mechanism. Thermogravimetric analysis and differential scanning calorimetry (TG-DSC) were employed to test the oxidation properties of coal samples treated with DTE, NaCl, MgCl2, and CaCl2 inhibitors, and the reaction mechanisms and kinetic parameters in the high-temperature stage of coal oxidation were determined. The results revealed that the inhibition of the four inhibitors was similar in the initial period of the coal oxidation, DTE increased the cracking temperature of the coal by 37 °C, mass loss was a minimum when reaching the ignition temperature, and inhibition was better than the other inhibitors at the low temperature. DTE had higher thermal stability and played a stable role in suppression at the high temperature, while chlorine salt inhibitors promoted the oxidative exothermic reaction. DTE coal sample absorbed forty times more heat during the endothermic stage than raw coal, ten times more than MgCl2, and released a minimum of heat. In the decomposition and combustion stages, the reaction mechanism of coal and oxygen conformed to the three-dimensional diffusion Z.-L.-T. equation, and the apparent activation energy of the DTE-treated coal sample was about 40 kJ/mol higher than raw coal.

Prognostic value of systemic immune inflammation index and geriatric nutrition risk index in early-onset colorectal cancer.

Background: Systemic nutritional and inflammatory markers, which are easy to measure are associated with the progression and prognosis of many cancers. Nevertheless, among the various available indicators, optimal prognostic indicators for patients with early-onset colorectal cancer have not been identified. Therefore, the aim of this study was to identify optimal nutritional and inflammatory markers for early-onset colorectal cancer and examine the relationship between systemic nutritional and inflammatory markers before treatment and survival in patients with early-onset colorectal cancer. Methods: We retrospectively collected data from 236 eligible patients with early-onset colorectal cancer. Area under the prognostic curve (AUC) and concordance index (C-index) were used to compare seven systemic nutritional and inflammatory markers to identify the optimal inflammatory immune markers. Univariate and multivariate COX regression analyses were used to evaluate the prognostic value of indicators in the total study population and different subgroups. Results: The AUC and C-index showed that the systemic immune inflammation index (SII) and geriatric nutrition risk index (GNRI) had higher prognostic values than other systemic nutritional and inflammatory indicators. Compared with patients in the low SII group, those in the high SII group had lower overall survival (HR, 4.42, 95% CI, 2.36-8.27, p = 0.000). Compared with patients in the high GNRI group, those in the low GNRI group had lower overall survival (HR, 0.33, 95% CI, 0.19-0.56, p = 0.000). SII was negatively associated with GNRI (R = -0.3, p < 0.001), and both were correlated with the tumor stage. Conclusion: SII and GNRI are suitable nutritional and inflammatory factors for predicting OS in patients with early-onset colorectal cancer; high SII and low GNRI were correlated with worse prognoses. Identifying the high inflammatory state and low nutritional state of patients before surgery and conducting active and timely therapeutic interventions could improve patient prognosis.

Targeting tumor immunosuppressive microenvironment for pancreatic cancer immunotherapy: Current research and future perspective.

Pancreatic cancer is one of the most malignant tumors with increased incidence rate. The effect of surgery combined with chemoradiotherapy on survival of patients is unsatisfactory. New treatment strategy such as immunotherapy need to be investigated. The accumulation of desmoplastic stroma, infiltration of immunosuppressive cells including myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs), as well as tumor associated cytokine such as TGF-ß, IL-10, IL-35, CCL5 and CXCL12 construct an immunosuppressive microenvironment of pancreatic cancer, which presents challenges for immunotherapy. In this review article, we explore the roles and mechanism of immunosuppressive cells and lymphocytes in establishing an immunosuppressive tumor microenvironment in pancreatic cancer. In addition, immunotherapy strategies for pancreatic cancer based on tumor microenvironment including immune checkpoint inhibitors, targeting extracellular matrix (ECM), interfering with stromal cells or cytokines in TME, cancer vaccines and extracellular vesicles (EVs) are also discussed. It is necessary to identify an approach of immunotherapy in combination with other modalities to produce a synergistic effect with increased response rates in pancreatic cancer therapy.

How does HbA1c predict mortality and readmission in patients with heart failure? A protocol for systematic review and meta-analysis.

BACKGROUND: Accumulating evidence suggests that HbA1c levels, a common clinical indicator of chronic glucose metabolism over the preceding 2-3 months, are independent risk factors for cardiovascular disease, including heart failure. However, conflicting evidence obscures clear cutoffs of HbA1c levels in various heart failure populations. The aim of this review is to assess the possible predictive value and optimal range of HbA1c on mortality and readmission in patients with heart failure. METHODS: A systematic and comprehensive search will be performed using PubMed, Embase, CINAHL, Scopus, and the Cochrane Library databases before December 2022 to identify relevant studies. All-cause mortality is the prespecified primary endpoint. Cardiovascular death and heart failure readmission are secondary endpoints of interest. We will only include prospective and retrospective cohort studies and place no restrictions on the language, race, region, or publication period. The ROBINS-I tool will be used to assess the quality of each included research. If there were sufficient studies, we will conduct a meta-analysis with pooled relative risks and corresponding 95% confidence intervals to evaluate the possible predictive value of HbA1c for mortality and readmission. Otherwise, we will undertake a narrative synthesis. Heterogeneity and publication bias will be assessed. If heterogeneity was significant among included studies, a sensitivity analysis or subgroup analysis will be used to explore the source of heterogeneity, such as diverse types of heart failure or patients with diabetes and non-diabetes. Additionally, we will conduct meta-regression to examine the time-effect and treatment-effect modifiers on all-cause mortality compared between different quantile of HbA1c levels. Finally, a restricted cubic spline model may be used to explore the dose-response relationship between HbA1c and adverse outcomes. DISCUSSION: This planned analysis is anticipated to identify the predictive value of HbA1c for mortality and readmission in patients with heart failure. Improved understanding of different HbA1c levels and their specific effect on diverse types of heart failure or patients with diabetes and non-diabetes is expected to be figured out. Importantly, a dose-response relationship or optimal range of HbA1c will be determined to instruct clinicians and patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration details: CRD42021276067.

Patient-Derived Tumor Organoids Can Predict the Progression-Free Survival of Patients With Stage IV Colorectal Cancer After Surgery.

BACKGROUND: Recent studies have shown patient-derived tumor organoids can predict the drug response of patients with cancer. However, the prognostic value of patient-derived tumor organoid-based drug tests in predicting the progression-free survival of patients with stage IV colorectal cancer after surgery remains unknown. OBJECTIVE: This study aimed to explore the prognostic value of patient-derived tumor organoid-based drug tests in patients with stage IV colorectal cancer after surgery. DESIGN: Retrospective cohort study. SETTINGS: Surgical samples were obtained from patients with stage IV colorectal cancer at the Nanfang Hospital. PATIENTS: A total of 108 patients who underwent surgery with successful patient-derived tumor organoid culture and drug testing were recruited between June 2018 and June 2019. INTERVENTIONS: Patient-derived tumor organoid culture and chemotherapeutic drug testing. MAIN OUTCOMES MEASURES: Progression-free survival. RESULTS: According to the patient-derived tumor organoid-based drug test, 38 patients were drug sensitive and 76 patients were drug resistant. The median progression-free survival was 16.0 months in the drug-sensitive group and 9.0 months in the drug resistant group ( p < 0.001). Multivariate analyses showed that drug resistance (HR, 3.38; 95% CI, 1.84-6.21; p < 0.001), right-sided colon (HR, 3.50; 95% CI, 1.71-7.15; p < 0.001), mucinous adenocarcinoma (HR, 2.47; 95% CI, 1.34-4.55; p = 0.004), and non-R0 resection (HR, 2.70; 95% CI, 1.61-4.54; p < 0.001) were independent predictors of progression-free survival. The new patient-derived tumor organoid-based drug test model, which includes the patient-derived tumor organoid-based drug test, primary tumor location, histological type, and R0 resection, was more accurate than the traditional clinicopathological model in predicting progression-free survival ( p = 0.001). LIMITATIONS: A single-center cohort study. CONCLUSIONS: Patient-derived tumor organoids can predict progression-free survival in patients with stage IV colorectal cancer after surgery. Patient-derived tumor organoid drug resistance is associated with shorter progression-free survival, and the addition of patient-derived tumor organoid drug tests to existing clinicopathological models improves the ability to predict progression-free survival.

A prognostic nomogram for predicting overall survival in colorectal mucinous adenocarcinoma patients based on the SEER database.

A nomogram was constructed to predict the survival of patients with colorectal mucinous adenocarcinoma based on data extracted from the Surveillance, Epidemiology and End Result (SEER) database. Data collected between 2010 and 2018 were obtained from the SEER database. The log-rank test and multivariate Cox regression were performed to identify the independent prognostic factors for overall survival, which were further used to construct a nomogram model to predict 1-, 3-, and 5-year overall survival. In total, 10846 patients diagnosed with colorectal mucinous adenocarcinoma were enrolled in the study. The following 11 variables were associated with survival and were further incorporated into the nomogram: age at diagnosis, primary site, grade, tumour size, lymph node dissection, T stage, N stage, M stage, surgery for primary site, chemotherapy, and household income. The concordance index (C-index) value was 0.725 (95% confidence interval 0.716-0.734), and the receiver operating characteristic curves and calibration curves showed satisfactory predictive accuracy. Both the C-index and time-independent area under the curve values were greater than those of the American Joint Committee on Cancer 7th TNM classification system (both P < 0.001). In the validation group, the results were consistent with those of the training group, with a C-index value of 0.726 (95% confidence interval 0.713-0.739). This study constructed a practical nomogram to predict 1-, 3-, and 5-year OS for patients with colorectal colorectal mucinous adenocarcinoma based on SEER data.

Effect of the home care model in orthopedic wounds management.

Objective: To explore the effect of home care on orthopedic wound management. Materials and Methods: Patients with orthopedic wounds admitted from January 2020 to December 2022 were divided into a control group and a nursing group, with 23 cases in each group. After discharge, the control group was given routine health guidance and the nursing group was given home care. The mood score of the two groups of patients was evaluated, the time and cost were compared, and the patients' degree of trust and satisfaction with the medical staff were investigated. Results: The patients received home care had higher scores in mood, degree of trust and satisfaction with medical staff, and spent less time (P < .05). However, the cost was significantly higher than that of the control group (P < .05). Conclusions: Home care for patients with orthopedic wounds can significantly reduce the time spent on medical treatment. Moreover, improve patients' moods and trust and satisfaction with medical staff in a certain extent. However, better service often means more economic cost.

Selumetinib - a potential small molecule inhibitor for osteoarthritis treatment.

Objectives: Osteoarthritis (OA) is a common disease that mainly manifests as inflammation and destruction of cartilage and subchondral bone. Recently, necroptosis has been reported to play an important role in the development of OA. Selumetinib displays a contrasting expression pattern to necroptosis-related proteins. The present study aimed to investigate the potential therapeutic effects of selumetinib in OA process. Methods: In vitro experiments, interleukin-1ß (IL-1ß) was used to induce necroptosis of chondrocytes. We used high-density cell culture, Western Blot and PT-PCR to observe the effect of different concentrations of selumetinib on the extracellular matrix of cartilage. Afterwards, we visualized the effect of selumetinib on osteoclast formation by TRAP staining and F-actin rings. In vivo experiment, we induced experimental osteoarthritis in mice by surgically destabilizing the medial meniscus (DMM) while administering different concentrations of selumetinib intraperitoneally. Results: Selumetinib promoted cartilage matrix synthesis and inhibited matrix decomposition. We found that selumetinib exerted a protective function by inhibiting the activation of RIP1/RIP3/MLKL signaling pathways in chondrocytes. Selumetinib also inhibited the activation of RANKL-induced NF-κB and MAPK signaling pathways in BMMs, thereby interfering with the expression of osteoclast marker genes. In the DMM-induced OA model, a postsurgical injection of selumetinib inhibited cartilage destruction and lessened the formation of TRAP-positive osteoclasts in subchondral bone. Conclusion: Selumetinib can protect chondrocytes by regulating necroptosis to prevent the progression of OA and reduce osteoclast formation. In summary, our findings suggest that selumetinib has potential as a therapeutic agent for OA.

Epidemiological analysis of septic shock in the plateau region of China.

Purpose: Little epidemiological data exist on patients with severe infection in the plateau region of China, and the data that do exist are lacking in quality. Using the medical records of patients with severe infection in the Department of Intensive Medicine (intensive care unit; ICU) of the People's Hospital of Tibet Autonomous Region, this study analyzed the epidemiological and clinical characteristics of patients with septic shock in plateau area (Tibet), with the ultimate aim of reducing the incidence and mortality from this condition. Methods: Clinical data on 137 patients with septic shock in the studied ICU from November 2017 to October 2019 were retrospectively analyzed using SPSS, Version 21.0. Results: Among the 137 patients with septic shock, there were 47 survivors and 90 in-hospital or post-discharge deaths. There were 91 male patients and 46 female patients. The incidence of septic shock was 11.3%, and mortality rate was 65.7%. Median age was 55 years old, median APACHE-II score on the day of admission was 17, median SOFA score was 11, and median number of organ injuries was one. APACHE-II score (P = 0.02), SOFA score (P < 0.001), and the number of organ injuries (P < 0.001) were higher among patients who died than among survivors. The infections were mainly pulmonary and abdominal, and the main pathogen was gram-negative bacteria. Conclusion: The incidence and mortality of septic shock in ICU wards in Tibet are very high. The APACHE-II score, SOFA score, and the number of organ damage on the first day after diagnosis are independent risk factors for septic shock. To some extent, this study reflects the epidemiological characteristics of septic shock in the plateau region of China (≥ 3,650 m above sea level) and provides data that can support the prevention and treatment of sepsis in the future. More and deeper epidemiological studies of septic shock are necessary.

Efficacy and safety of triplet chemotherapy plus anti-EGFR agents in metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: To date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported in studies exploring the efficacy of triplet chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) target agents. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from December 2004 to October 2021 for studies examining the efficacy of triplet chemotherapy plus anti-EGFR target agents in mCRC patients. The primary outcomes were the objective response rate (ORR) and R0 resection rate (R0RR), and the secondary outcomes were median progression-free survival (mPFS), median overall survival (mOS), and toxicity. Data were analyzed with R software 4.1.2. RESULTS: Fourteen studies comprising 762 patients with mCRC were included in this meta-analysis. Analysis with a random effects model revealed that after treatment with triplet chemotherapy plus anti-EGFR target agents, the pooled ORR was 82% (95% CI= 76-88%, I2= 76%), and the pooled R0RR of colorectal liver metastasis (CLM) was 59% (95% CI= 49-68%, I2= 60%). The mPFS ranged from 9.5 to 17.8 months, and the mOS ranged from 24.7 to 62.5 months. A total of 648 grade 3 or 4 adverse events were reported; the most commonly reported events were diarrhea (174/648), neutropenia (157/648), and skin toxicity (95/648), which had pooled prevalence rates of 29% (95% CI= 20-39%, I2= 84%), 28% (95% CI= 20-37%, I2= 77%), and 17% (95% CI= 11-24%, I2= 66%), respectively. CONCLUSIONS: Triplet chemotherapy plus anti-EGFR agents therapy seems to be capable of increasing the ORR of mCRC patients and the R0RR of CLM patients. The toxicity of this treatment is manageable. High-quality randomized controlled trial (RCT) studies are required for further validation.