Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Central venous-to-arterial carbon dioxide partial pressure difference as a guiding parameter for cardiotonic drug administration in patients with early-stage septic shock.

OBJECTIVE: This study aimed to investigate the effect of the central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) on the administration of cardiotonic drugs in patients with early-stage septic shock. METHODS: A retrospective study was conducted on 120 patients suffering from septic shock. At admission, the left ventricular ejection fraction (LVEF) and Pcv-aCO2 of the patients were obtained. On the premise of mean arterial pressure (MAP) ≥ 65 mmHg, the patients were divided into two groups according to the treatment approaches adopted by different doctors-Control group: LVEF ≤50%; Observation group: Pcv-aCO2 ≥ 6. Both groups received cardiotonic therapy. RESULTS: The two groups of patients had similar general conditions and pre-resuscitation conditions (P > 0.05). Compared to the Control group, the Observation group had a higher MAP, Lac clearance rate, and urine output after six hours of resuscitation (P < 0.05), but a lower absolute value of Lac, total fluid intake in 24 hours, and a lower number of patients receiving renal replacement therapy during hospitalization (P < 0.05). After six hours of resuscitation, the percentages of patients meeting central venous oxygen saturation and central venous pressure targets were not significantly different between the Control and Observation groups (P > 0.05). There was no difference in the 28-day mortality rate between the two groups (P > 0.05). CONCLUSION: Pcv-aCO2 is more effective than LVEF in guiding the administration of cardiotonic drugs in the treatment of patients with septic shock.

Reliability and Validity of the Chinese Version of the Nurses' Cancer Pain Management Competency Scale.

BACKGROUND: The Nurses' Cancer Pain Management Competency Scale (NCPMCS) is a tool to explore nurses' competencies and subjective experiences in cancer pain management, and to help nurses understand their current shortcomings in cancer pain management. The scale, currently available only in English and translated into Chinese for wider adoption abroad, provides a tool for Chinese nurses to assess their level of cancer pain management. Furthermore, based on the scale's specific score, they can evaluate their lack of understanding about cancer pain management, advance research into this area, and enhance their capacity to control cancer pain while providing patient care. OBJECTIVE: The purpose of this study was to translate and localize the new scale, and to measure its reliability and validity. The study was also to provide a way to quickly and accurately measure the competency of cancer pain management among nursing staff in China. METHODS: The Bristling translation approach was used to translate, translate back, and culturally modify the English version of the cancer pain management competency scale for nurses to create the Chinese version. A convenience sample was used for the study, 220 clinical nurses from three Grade III hospitals in Zhengzhou, Henan Province, China, were chosen by convenience sampling. The Chinese version of the scale was used for this investigation. RESULTS: The Cancer Pain Management Competency Scale for Nurses has 14 items over 4 dimensions in its Chinese form. From the exploratory factor analysis, four common components were recovered; the cumulative variance rate was 81.994%, the scale's Cronbach's α coefficient was 0.902, and the Cronbach's α coefficient for each dimension ranged from 0.800 to 0.938. Retest reliability was 0.915, scale content validity was 0.865, and Spearman-Brown's broken half reliability was 0.808. CONCLUSION: Nurses' cancer pain management competency in clinics can be assessed using the Chinese version of the Nurses' Cancer Pain Management Competency Scale, which has strong validity and reliability.

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia.

BACKGROUND: Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously. METHODS: The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration. RESULTS: The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro. CONCLUSIONS: Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.

Association of Triglyceride Glucose-Derived Indexes with Recurrent Events Following Atherosclerotic Cardiovascular Disease.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indexes of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indexes shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion: This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

Combined treatment of All-trans retinoic acid with Tamoxifen suppresses ovarian cancer.

BACKGROUND: Ovarian cancer is a malignant tumor of the female reproductive system, and its mortality rate is as high as 70%. Estrogen receptor α (ERα)-positive ovarian cancer accounted for most of all ovarian cancer patients. ERα can promote the growth and proliferation of tumors. METHODS: The combined effect of All-trans retinoic acid (ATRA) and tamoxifen was obtained by the combination screening of tamoxifen and compound library by MTS. In addition, colony formation assay, flow cytometry analysis, immunofluorescence staining, quantitative real-time polymerase chain reaction (PCR), western blot, and tumor xenotransplantation models were used to further evaluate the efficacy of tamoxifen and ATRA in vitro and in vivo for ER-α-positive ovarian cancer. RESULTS: In our study, we found that All-trans retinoic acid (ATRA) can cooperate with tamoxifen to cause cell cycle arrest and apoptosis and inhibit ERα-positive ovarian cancer in vivo and in vitro. Further exploration of the mechanism found that ATRA can Inhibit genes related to the ERα signaling pathway, enhance the sensitivity of ERα-positive ovarian cancer cells to tamoxifen, and ascertain the effectiveness of tamoxifen and ATRA as treatments for ovarian cancer with an ERα-positive status. CONCLUSION: Combination of ATRA and tamoxifen is a new way for the treatment of ERα-positive ovarian cancer.

Correction: Magnaporthe oryzae fimbrin organizes actin networks in the hyphal tip during polar growth and pathogenesis.

[This corrects the article DOI: 10.1371/journal.ppat.1008437.].

Stochastic processes shape microbial community assembly in biofilters: Hidden role of rare taxa.

Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation.

Single and combined association between brominated flame retardants and cardiovascular disease: a large-scale cross-sectional study.

Introduction: The single and combined association between brominated flame retardants (BFRs) and cardiovascular diseases (CVD) has remained unelucidated. This research aimed at exploring the associations between mixture of BFRs and CVD. Methods: This research encompassed adult participants from the National Health and Nutrition Examination Survey in 2005-2016. The weighted quantile sum (WQS) model and quantile g-computation (QGC) model were applied to examine the combined effects of BFRs mixture on CVD. Results: In this research, overall 7,032 individuals were included. In comparison with the lowest quartile, the highest quartile of PBB153 showed a positive association with CVD, with odds ratio (OR) values and 95% confidence intervals (CI) of 19.2 (10.9, 34.0). Furthermore, the acquired data indicated that PBB153 (OR: 1.23; 95% CI: 1.02, 1.49), PBB99 (OR: 1.29; 95% CI: 1.06, 1.58), and PBB154 (OR: 1.29; 95% CI: 1.02, 1.63) were linked to congestive heart failure. PBB153 was also related to coronary heart disease (OR: 1.29; 95% CI: 1.06, 1.56). Additionally, a positive correlation between the BFRs mixture and CVD (positive model: OR: 1.23; 95% CI: 1.03, 1.47) was observed in the weighted quantile sum (WQS) model and the quantile g-computation (QGC) model. Discussion: Therefore, exposure to BFRs has been observed to heighten the risk of cardiovascular disease in US adults, particularly in the case of PBB153. Further investigation is warranted through a large-scale cohort study to validate and strengthen these findings.

In Situ Root Dataset Expansion Strategy Based on an Improved CycleGAN Generator.

The root system plays a vital role in plants' ability to absorb water and nutrients. In situ root research offers an intuitive approach to exploring root phenotypes and their dynamics. Deep-learning-based root segmentation methods have gained popularity, but they require large labeled datasets for training. This paper presents an expansion method for in situ root datasets using an improved CycleGAN generator. In addition, spatial-coordinate-based target background separation method is proposed, which solves the issue of background pixel variations caused by generator errors. Compared to traditional threshold segmentation methods, this approach demonstrates superior speed, accuracy, and stability. Moreover, through time-division soil image acquisition, diverse culture medium can be replaced in in situ root images, thereby enhancing dataset versatility. After validating the performance of the Improved_UNet network on the augmented dataset, the optimal results show a 0.63% increase in mean intersection over union, 0.41% in F1, and 0.04% in accuracy. In terms of generalization performance, the optimal results show a 33.6% increase in mean intersection over union, 28.11% in F1, and 2.62% in accuracy. The experimental results confirm the feasibility and practicality of the proposed dataset augmentation strategy. In the future, we plan to combine normal mapping with rendering software to achieve more accurate shading simulations of in situ roots. In addition, we aim to create a broader range of images that encompass various crop varieties and soil types.

Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction.

OBJECTIVES: Stress-related glycemic indicators, including admission blood glucose (ABG), stress-hyperglycemia ratio (SHR), and glycemic gap (GG), have been associated with worse outcomes after acute myocardial infarction (AMI). However, data regarding their prognostic value in the oldest old with AMI are unavailable. Therefore, this study aimed to investigate the association of stress-related glycemic indicators with short- and long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with AMI. METHODS: In this prospective study, a total of 933 consecutive old patients with AMI admitted to FuWai hospital (Beijing, China) were enrolled. On admission, ABG, SHR, and GG were assessed and all participants were classified according to their quartiles. Kaplan-Meier, restricted cubic splines (RCS), and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term follow-up. RESULTS: During an average of 1954 patient-years of follow-up, a total of 250 cardiovascular deaths were recorded. Kaplan-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and GG. After adjusting for potential covariates, patients in quartile 4 of ABG, SHR, and GG had a respective 1.67-fold (95% CI: 1.03-2.69; P = 0.036), 1.80-fold (95% CI: 1.16-2.79; P = 0.009), and 1.78-fold (95% CI: 1.14-2.79; P = 0.011) higher risk of long-term CVM risk compared to those in the reference groups (quartile 1 of ABG and quartile 2 of SHR and GG). Furthermore, RCS suggested a J-shaped relationship of ABG and a U-shaped association of SHR and GG with long-term CVM. Additionally, we observed similar associations of these acute glycemic parameters with 30-day CVM. CONCLUSIONS: Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and long-term CVM among the oldest old with AMI, suggesting that they may be useful for risk stratification in this special population.

An online survey on public awareness of drug clinical trials in inland cities of northern China.

Objective: The aims of this survey were to investigate the public awareness of drug clinical trials (DCTs) and willingness to participate the DCTs, and provide references for propaganda and science popularization of DCTs. Methods: A self-designed questionnaire named "an online survey questionnaire on public awareness of DCTs" was used to conduct an online survey from January to March 2022. The demographic characteristics and the response of participants to the awareness and willingness to participate the DCTs were collected. The factors affecting the public awareness of DCTs were analyzed by single factor and binary logistic regression analysis. Results: One thousand three hundred eighty valid questionnaires were collected, and the respondents' awareness rate of DCTs was 61.1%. Thirteen demographic characteristics including age, gender, education, occupation, work fields, household type, marital status, city type, income, medical insurance, medical expenditure, pressure to seek medical care, financial pressure, both significantly affected the qualified rate of participants' awareness of DCTs (p < 0.001) by single factor analysis. Binary logistic regression analysis indicated that education level, work fields, city type, medical insurance, and medical expenditure affected independently the participants' awareness rate of DCTs (p < 0.001). 52.9% of the participants were willing to take part in DCTs. "to promote medical progress" (54.4%) or "believe doctors" (31.1%) were the most frequent reasons for subjects participating in DCTs. Conclusion: The public awareness rate of DCTs and the willingness to participate in drug clinical were significantly affected by the demographic characteristics of subjects. Thus, targeting the needs of the public, propaganda, and science popularization of DCTs should be carried out and served public health.

Range-Wide Phylogeography and Ecological Niche Modeling Provide Insights into the Evolutionary History of the Mongolian Racerunner (Eremias argus) in Northeast Asia.

The Mongolian racerunner, Eremias argus, is a small lizard endemic to Northeast Asia that can serve as an excellent model for investigating how geography and past climate change have jointly influenced the evolution of biodiversity in this region. To elucidate the processes underlying its diversification and demography, we reconstructed the range-wide phylogeographic pattern and evolutionary trajectory, using phylogenetic, population genetic, landscape genetic, Bayesian phylogeographic reconstruction and ecological niche modeling approaches. Phylogenetic analyses of the mtDNA cyt b gene revealed eight lineages that were unbounded by geographic region. The genetic structure of E. argus was mainly determined by geographic distance. Divergence dating indicated that E. argus and E. brenchleyi diverged during the Mid-Pliocene Warm Period. E. argus was estimated to have coalesced at~0.4351 Ma (Marine Isotope Stage 19). Bayesian phylogeographic diffusion analysis revealed out-of-Inner Mongolia and rapid colonization events from the end of the Last Interglacial to the Last Glacial Maximum, which is consistent with the expanded suitable range of the Last Glacial Maximum. Pre-Last Glacial Maximum growth of population is presented for most lineages of E. argus. The Glacial Maximum contraction model and the previous multiple glacial refugia hypotheses are rejected. This may be due to an increase in the amount of climatically favorable habitats in Northeast Asia. Furthermore, E. argus barbouri most likely represents an invalid taxon. The present study is the first to report a range-wide phylogeography of reptiles over such a large region in Northeast Asia. Our results make a significant contribution towards understanding the biogeography of the entire Northeast Asia.

Is recovery enhancement after gastric cancer surgery really a safe approach for elderly patients?

BACKGROUND: This study aimed to evaluate the safety of enhanced recovery after surgery (ERAS) in elderly patients with gastric cancer (GC). AIM: To evaluate the safety of ERAS in elderly patients with GC. METHODS: The PubMed, EMBASE, and Cochrane Library databases were used to search for eligible studies from inception to April 1, 2023. The mean difference (MD), odds ratio (OR) and 95% confidence interval (95%CI) were pooled for analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores. We used Stata (V.16.0) software for data analysis. RESULTS: This study consists of six studies involving 878 elderly patients. By analyzing the clinical outcomes, we found that the ERAS group had shorter postoperative hospital stays (MD = -0.51, I2 = 0.00%, 95%CI = -0.72 to -0.30, P = 0.00); earlier times to first flatus (defecation; MD = -0.30, I² = 0.00%, 95%CI = -0.55 to -0.06, P = 0.02); less intestinal obstruction (OR = 3.24, I2 = 0.00%, 95%CI = 1.07 to 9.78, P = 0.04); less nausea and vomiting (OR = 4.07, I2 = 0.00%, 95%CI = 1.29 to 12.84, P = 0.02); and less gastric retention (OR = 5.69, I2 = 2.46%, 95%CI = 2.00 to 16.20, P = 0.00). Our results showed that the conventional group had a greater mortality rate than the ERAS group (OR = 0.24, I2 = 0.00%, 95%CI = 0.07 to 0.84, P = 0.03). However, there was no statistically significant difference in major complications between the ERAS group and the conventional group (OR = 0.67, I2 = 0.00%, 95%CI = 0.38 to 1.18, P = 0.16). CONCLUSION: Compared to those with conventional recovery, elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.

Predictive value of red blood cell distribution width and hematocrit for short-term outcomes and prognosis in colorectal cancer patients undergoing radical surgery.

BACKGROUND: Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer, the prognostic value of hematocrit for colorectal cancer (CRC) patients has not been determined. The prognostic value of red blood cell distribution width (RDW) for CRC patients was controversial. AIM: To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery. METHODS: Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included. The short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared among the different groups. Cox analysis was also conducted to identify independent risk factors for OS and DFS. RESULTS: There were 4258 CRC patients who underwent radical surgery included in our study. A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group. There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group, respectively. Patients in the higher RDW group had more intraoperative blood loss (P < 0.01) and more overall complications (P < 0.01) than did those in the lower RDW group. Similarly, patients in the lower hematocrit group had more intraoperative blood loss (P = 0.012), longer hospital stay (P = 0.016) and overall complications (P < 0.01) than did those in the higher hematocrit group. The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis (TNM) stage I (OS, P < 0.05; DFS, P = 0.001) and stage II (OS, P = 0.004; DFS, P = 0.01) than the lower RDW group; the lower hematocrit group had worse OS and DFS for TNM stage II (OS, P < 0.05; DFS, P = 0.001) and stage III (OS, P = 0.001; DFS, P = 0.001) than did the higher hematocrit group. Preoperative hematocrit was an independent risk factor for OS [P = 0.017, hazard ratio (HR) = 1.256, 95% confidence interval (CI): 1.041-1.515] and DFS (P = 0.035, HR = 1.194, 95%CI: 1.013-1.408). CONCLUSION: A higher preoperative RDW and lower hematocrit were associated with more postoperative complications. However, only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery, while RDW was not.

Unconventional Surface Doping Effect on the Spin State of an Adsorbed Magnetic Molecule.

Magnetic molecules adsorbed on two-dimensional (2D) substrates have attracted broad attention because of their potential applications in quantum device applications. Experimental observations have demonstrated substantial alteration in the spin excitation energy of iron phthalocyanine (FePc) molecules when adsorbed on nitrogen-doped graphene substrates. However, the underlying mechanism responsible for this notable change remains unclear. To shed light on this, we employ an embedding method and ab initio quantum chemistry calculations to investigate the effects of surface doping on molecular properties. Our study unveils an unconventional chemical bonding at the interface between the FePc molecule and the N-doped graphene. This bonding interaction, stronger than non-covalent interactions, significantly modifies the magnetic anisotropy energy of the adsorbed molecule, consistent with experimental observations. These findings provide valuable insights into the electronic and magnetic properties of molecules on 2D substrates, offering a promising pathway for precise manipulation of molecular spin states.

Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

Molecular mechanism and intervention measures of microvascular complications in diabetes.

Objective: In this article, the epidemiology, molecular mechanism of occurrence and development, risk factors, and treatment of diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy were discussed, providing the theoretical basis for more accurate elucidation of the pathogenesis and treatment of diabetic microvascular complications. Methods: The electronic database of PubMed was searched, and retrieved papers were screened for eligibility by two independent reviewers. Data were extracted using a standardized data extraction form and the quality of included papers was assessed. Results: Thirty-eight articles were included. Diabetes nephropathy, diabetes peripheral neuropathy, and diabetes retinopathy are the most common and serious microvascular complications of diabetes in clinical patients. Renin-angiotensin system blockers, beta drugs, statins, antivascular endothelial growth factor drugs, and antioxidants can inhibit the occurrence of microvascular complications in diabetes. Conclusions: However, there has been no breakthrough in the treatment of diabetic microvascular complications. Therefore, prevention of diabetic microvascular complications is more important than treatment.

In situ chemoimmunotherapy hydrogel elicits immunogenic cell death and evokes efficient antitumor immune response.

BACKGROUND: Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application. METHODS: Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated. RESULTS: This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. CONCLUSIONS: Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.