Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids.

Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.

High albumin-bilirubin grade predicts worse short-term complications in gastric cancer patients with metabolic syndrome: a retrospective study.

Background: Preoperative albumin-bilirubin (ALBI) grade has been proposed and applied in recent years to evaluate the prognosis of liver cancer, but its role in gastric cancer (GC) is still unclear. This research aimed to examine the prognostic value of ALBI grade after gastrectomy among patients with GC complicated with metabolic syndrome (MetS). Methods: There were 628 patients who received radical resection for GC. Laboratory data and short-term results were collected prospectively, and preoperative ALBI grades were calculated from the albumin and bilirubin levels. The appropriate ALBI cutoff value was calculated by receiver operating characteristic (ROC) curve analysis, which we used to put patients into high (>-2.54) and low (≤-2.54) ALBI grade groups. The differences between the short-term complication rates of the two groups were analyzed with the chi-square test. Results: Of the included patients, 133 (21.2%) and 495 (78.8%) had high and low ALBI grades, respectively. A high ALBI grade (P=0.001), body mass index (BMI) ≥25 kg/m2 (P=0.001), and hypertension (P=0.018) were independent risk factors for postoperative complications. In GC patients with and without MetS, the high ALBI subgroup showed more overall complications than the low ALBI subgroup (P=0.028 and P=0.001). Among GC patients with MetS, those with a high ALBI grade showed a higher incidence of serious complications than those with a low ALBI grade (P=0.001); a similar, nonsignificant trend occurred in non-MetS patients (P=0.153). Conclusions: The preoperative ALBI grade is important in the prognosis of GC patients with MetS after gastrectomy. GC patients with MetS can lower their incidence of serious complications by adjusting their preoperative ALBI grade.

Detection of Rickettsia spp. and Anaplasma ovis in Melophagus ovinus from southern Xinjiang, China.

Melophagus ovinus is a hematophagous insect that is distributed worldwide and plays a crucial role in transmitting disease-causing pathogens. From June 2021 to March 2022, a total of 370 M. ovinus were collected from 11 sampling points in southern Xinjiang, China. The specimens were identified using morphological and molecular analyses. Rickettsia spp. and Anaplasma ovis were detected from all the samples using seven Rickettsia-specific genetic markers and the msp-4 gene of A. ovis. Approximately 11% of the M. ovinus specimens were positive for Rickettsia spp., and Candidatus Rickettsia barbariae was the most predominant species (35/41; 85.4%), while R. massiliae was least prevalent (6/41; 14.6%). Approximately 10.5% (39/370) of the M. ovinus specimens were positive for A. ovis of genotype III, which was co-detected with Candidatus R. barbariae in M. ovinus (3/370; 0.8%). To the best of our knowledge, this is the first report of the detection of R. massiliae and Candidatus R. barbariae in M. ovinus globally. The detection and control of insect-borne diseases originating from M. ovinus should be strengthened in southern Xinjiang, an area important to animal husbandry and production.

Detection of Babesia Spp., Theileria Spp., and Anaplasma Ovis in Ornithodoros Lahorensis from Southern Xinjiang, China.

Introduction: Ticks are blood-sucking arthropods that have negative economic impacts and can spread a variety of diseases through their bites. There are few reports on soft ticks (Acari: Argasidae) and tick-borne pathogens in southern Xinjiang, China. This investigation supplements the available information for this region and is concerned with an argasid tick, apicomplexan parasites of the Babesia and Theileria genera and a bacterium of the Anaplasma genus. Material and Methods: In this study, 330 soft ticks were collected from nine sampling sites in southern Xinjiang between 2020 and 2021. The ticks were identified according to their morphological characteristics and confirmed as Ornithodoros lahorensis using mitochondrial 16S rDNA sequences. Babesia and Theileria were identified at the species level based on two fragments of the 18S rRNA gene, and one set of primers targeting the 16S rRNA gene was used to identify the Anaplasma genus. Results: Among the 330 samples, one Babesia species (Babesia sp.), two Theileria species (T. ovis and T. annulata), and one Anaplasma (A. ovis) species were detected. Conclusion: This study provides fundamental evidence for the occurrence of Babesia, Theileria and Anaplasma spp. in soft ticks. To the best of our knowledge, this is the first report of the detection of Babesia sp. and T. annulata in O. lahorensis. Therefore, the potential threat of soft ticks to livestock and humans should not be ignored.

Distribution and Molecular Epidemiology of Anaplasma ovis in Melophagus ovinus and Small Ruminants in Border Regions of South Xinjiang, China.

Background: Anaplasma ovis are obligate intracellular bacteria that can endanger human and animal health, and they can be transmitted by arthropod vectors, such as Melophagus ovinus and ticks. Materials and Methods: In this study, 433 specimens, including 370 M. ovinus and 63 sheep blood samples, were collected from nine districts of South Xinjiang to investigate the distribution and molecular epidemiology of A. ovis in M. ovinus and small ruminant. Results: DNA of A. ovis was detected in 109 (25.2%, 109/433) of the 433 samples using PCR and sequencing. The analysis of A. ovis msp4 sequences revealed four different genotypes, including genotype III (47.7%; 52/109), GB3 (34.0%; 37/109), AoGOv3 (15.6%; 17/109), and XJ9 (2.8%; 3/109). Conclusions: To the best of our knowledge, A. ovis genotypes GB3, AoGOv3, and XJ9 detected in this study are the first to be reported in M. ovinus, and our data indicate that XJ9 is a novel A. ovis genotype presented herein for the first time. These findings provide important references for the new understanding and prevention of A. ovis in border counties in China.

The Association Between Visceral Obesity and Postoperative Outcomes in Elderly Patients With Colorectal Cancer.

Background: The impact of visceral obesity on the postoperative complications of colorectal cancer in elderly patients has not been well studied. This study aims to explore the influence of visceral obesity on surgical outcomes in elderly patients who have accepted a radical surgery for colorectal cancer. Methods: Patients aged over 65 year who had undergone colorectal cancer resections from January 2015 to September 2020 were enrolled. Visceral obesity is typically evaluated based on visceral fat area (VFA) which is measured by computed tomography (CT) imaging. Univariate and multivariate analyses were performed to analyze parameters related to short-term outcomes. Results: A total of 528 patients participated in this prospective study. Patients with visceral obesity exhibited the higher incidence of total (34.1% vs. 18.0%, P < 0.001), surgical (26.1% vs. 14.6%, P = 0.001) and medical (12.6% vs. 6.7%, P = 0.022) complications. Based on multivariate analysis, visceral obesity and preoperative poorly controlled hypoalbuminemia were considered as independent risk factors for postoperative complications in elderly patients after colorectal cancer surgery. Conclusions: Visceral obesity, evaluated by VFA, was a crucial clinical predictor of short-term outcomes after colorectal cancer surgery in elderly patients. More attentions should be paid to these elderly patients before surgery.

ZIC2 promotes colorectal cancer growth and metastasis through the TGF-ß signaling pathway.

ZIC2 is involved in the tumor progression of many types of cancers. The role of ZIC2 in the metastasis of colorectal cancer and its mechanism are not yet clear. In this study, we found that high ZIC2 expression was not only associated with poor prognosis, relapse-free survival and advanced metastasis but was also an independent prognostic factor in colorectal cancer patients. Moreover, ZIC2 knockdown inhibited cell proliferation, migration and invasion, while the upregulation of ZIC2 had the opposite effect in vitro. ZIC2 overexpression induced TGF-ß1 expression and increased Smad3 phosphorylation. The carcinogenic effects of elevated ZIC2 expression can be eliminated by interfering with the TGF-ß1 receptor with inhibitors. This further verified the promoting effect of ZIC2 on the TGF-ß signaling pathway. In vivo experiments have also confirmed that ZIC2 can promote liver metastases of colorectal cancer. The results suggest that ZIC2 is associated with poor prognosis and relapse-free survival in colorectal cancer patients. Moreover, ZIC2 promoted colorectal cancer progression and metastasis by activating the TGF-ß signaling pathway. Hence, ZIC2 is expected to be a new therapeutic and prognostic target for colorectal cancer in the future.

Global leadership initiative in malnutrition (GLIM) criteria using hand-grip strength adequately predicts postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer.

BACKGROUND: The present study aims to investigate whether malnutrition defined by the Global Leadership Initiative in Malnutrition (GLIM) criteria using hand-grip strength (HGS) adequately predict postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer in a similar manner to GLIM-defined malnutrition using skeletal muscle index (SMI). METHODS: Patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included in this study. Clinical data were prospectively collected. Malnutrition was diagnosed based on the two-step approach following the GLIM criteria. Skeletal muscle mass was assessed using SMI based on abdominal computed tomography (CT) scans, or assessed using HGS. RESULTS: A total of 1359 patients were included in this study, in which 36.2% of the patients were at risk of malnutrition (Nutritional Risk Screening 2002 scores ≥3). The incidence of malnutrition was 28.2% and 27.5% using SMI and HGS, respectively. There was a high agreement between the two criteria of malnutrition (kappa = 0.863, P < 0.001). Both of the two criteria of malnutrition were independently associated with postoperative complications (SMI-GLIM, P = 0.041; HGS-GLIM, P = 0.023), overall survival (P < 0.001, both), and disease-free survival (P < 0.001, both), with similar odds ratio or hazard ratio after adjusting for the same confounding variables. HGS-GLIM malnutrition (P = 0.046) but not SMI-GLIM malnutrition (P = 0.270) was associated with a higher incidence of severe complications. CONCLUSIONS: GLIM criteria using HGS is a useful tool to diagnose malnutrition and has a similar or even better predictive value for postoperative complications and long-term survival after radical gastrectomy for gastric cancer compared with GLIM criteria using SMI.

Effect of GLIM-defined malnutrition on postoperative clinical outcomes in patients with colorectal cancer.

BACKGROUND: Malnutrition is common in colorectal cancer patients. Malnutrition is recognized as a risk factor for adverse postoperative outcomes, yet there are no consistent diagnostic criteria for it. Thus, the Global Leadership Initiative on Malnutrition published new universal criteria. We aimed to investigate the prevalence of malnutrition with the application of Global Leadership Initiative on Malnutrition criteria, and explore the correlations between Global Leadership Initiative on Malnutrition-defined malnutrition and postoperative clinical outcomes in colorectal cancer patients. METHODS: We included a cohort of 918 patients who underwent radical resection surgery for colorectal cancer from July 2014 to October 2019. Malnutrition was diagnosed based on the Global Leadership Initiative on Malnutrition criteria. The associations between nutritional status and postoperative clinical outcomes were analyzed by the Kaplan-Meier method, logistic and Cox regression analyses. RESULTS: Among the included patients, 23.6% were diagnosed as malnutrition based on Global Leadership Initiative on Malnutrition criteria. Global Leadership Initiative on Malnutrition-defined malnutrition was associated with total postoperative complications [odds ratio: 1.497 (1.042-2.152), P = 0.029]. Further, Global Leadership Initiative on Malnutrition-diagnosed malnutrition was an independent risk factor for overall survival [hazard ratio: 1.647 (1.048-2.587), P = 0.030] and disease-free survival [hazard ratio: 1.690 (1.169-2.441), P = 0.005]. CONCLUSIONS: The Global Leadership Initiative on Malnutrition criteria is effective to assess malnutrition. Preoperative malnutrition is associated with postoperative complications, overall survival and disease-free survival in colorectal cancer patients after radical resection surgery.

Double MOF gradually activated S bond induced S defect rich MILN-based Co(z)-NiMoS for efficient electrocatalytic overall water splitting.

Herein, cactus like nanorods with rich S defects and functional group MILN-based Co(z)-NiMoS are synthesized through a facile method. First, we prepared MIL-88B precursor to give a fairly dispersed frame structure, and then Con+ was doped into disulfides, which are rich in sulfur bonds, and the imidazole group was cleverly connected into graphitized carbon via self-etching of ZIF-67. The doping of Con+ and functional groups makes tiny changes in the sulfide lattice, which promotes the unsaturation degree of the S bond and activates it gradually. The prepared semi frame sulfide with a unique structure, on the one hand, ensures the hydrophilicity and multiple active specific surface area, which lays superior functions in morphology. On the other hand, coupling metals that have strong valence change ability and functional groups by active S bonds play an important role in the process of electrocatalytic reaction. Amazingly, disintegration and self-reconstruction of MILN-based Co(z)-NiMoS occurs during oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) due to the activation of the S bond, which provides a new perspective for the overall water splitting mechanism. The electrochemical results show that the MILN-based Co(z)-NiMoS electrocatalyst exhibits overpotentials of HER, OER, and overall water splitting (OWS) to be 169 mV, 170 mV, and 1.466 V, respectively, making it a promising electrode material for OWS applications.

The relationship between the GLIM-defined malnutrition, body composition and functional parameters, and clinical outcomes in elderly patients undergoing radical gastrectomy for gastric cancer.

OBJECTIVE: The present study aims to determine the correlations between Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition and body composition and functional parameters, and to comprehensively analyze the predictive value of GLIM-defined malnutrition for postoperative outcomes in the context of detailed measurement of body composition and functional parameters in elderly patients who underwent radical gastrectomy for gastric cancer. METHODS: Elderly patients (aged ≥65 years) who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index (SMI), skeletal muscle density (SMD), subcutaneous fat area (SFA), and visceral fat area (VFA) were analyzed using abdominal computed tomography (CT) images. Handgrip strength and 6-m gait speed were measured. RESULTS: A total of 597 elderly patients were included in this study, in which 45.7% were at risk of malnutrition identified using Nutritional Risk Screening 2002 (NRS 2002), and 34.5% were diagnosed with malnutrition. Patients with malnutrition had lower SMI, SMD, SFA, VFA, lower handgrip strength and gait speed. Low handgrip strength and age ≥80 years were independent risk factors for postoperative complications, rather than GLIM-defined malnutrition. GLIM-defined malnutrition was independently associated with overall survival and disease-free survival after adjusting to the body composition and functional parameters in the multivariate analyses. CONCLUSIONS: GLIM-defined malnutrition was a better predictive factor than single parameters of body composition or physical function for survival in elderly gastric cancer patients. Handgrip strength can be used as a supportive measure to further improve the definition of malnutrition.

Value of muscle quality, strength and gait speed in supporting the predictive power of GLIM-defined malnutrition for postoperative outcomes in overweight patients with gastric cancer.

BACKGROUND: The present study aims to investigate the prognostic value of Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition in overweight patients who underwent gastrectomy for gastric cancer, and to explore whether the addition of muscle quality, strength and gait speed could improve the predictive power for postoperative outcomes. METHODS: Overweight patients (body mass index (BMI) ≥23 kg/m2) who underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the two-step approach following the GLIM criteria. Skeletal muscle mass and quality was assessed using computed tomography (CT) determined skeletal muscle index (SMI) and skeletal muscle density (SMD), respectively. Hand-grip strength and 6-m gait speed were measured before surgery. RESULTS: A total of 587 overweight patients were included, in which 262 patients were identified as having obesity (BMI ≥25 kg/m2). The prevalence of malnutrition was 11.9% and 10.7% for overweight and obese patients, respectively. GLIM-defined malnutrition alone was not predictive for postoperative complications in overweight patients. The addition of low gait speed or muscle quality to GLIM-defined malnutrition led to a significant predictive value for postoperative complications. Low gait speed plus GLIM-defined malnutrition remained significant in the multivariate analysis. GLIM-defined malnutrition was predictive for overall survival (OS) and disease-free survival (DFS). Addition of low gait speed to GLIM-defined malnutrition increased the hazard ratio (HR) for the prediction of OS and DFS (univariate analysis: 2.880 vs. 2.238 for OS, 2.410 vs. 1.937 for DFS; multivariate analysis: 2.836 vs. 1.841 for OS, 2.433 vs. 1.634 for DFS). Addition of low hand-grip strength to GLIM-defined malnutrition led to a higher HR for the prediction of OS (2.144 vs. 1.841) in the multivariate analysis. CONCLUSION: Muscle quality, strength and gait speed added prognostic value to GLIM-defined malnutrition for the prediction of postoperative complications and/or survival in overweight patients who underwent radical gastrectomy for gastric cancer, especially gait speed, which could be incorporated into nutritional assessment protocols.

Measurement of muscle quantity/quality has additional predictive value for postoperative complications and long-term survival after gastrectomy for gastric cancer in patients with probable sarcopenia as defined by the new EWGSOP2 consensus: Analysis from a large-scale prospective study.

OBJECTIVES: We investigated whether measurement of muscle quantity/quality has additional predictive value for postoperative complications and long-term survival after gastrectomy for gastric cancer in patients with probable sarcopenia, as defined by the new European Working Group on Sarcopenia in Older People 2 consensus. METHODS: We conducted a prospective study of patients who underwent a radical gastrectomy for gastric cancer between August 2014 and June 2019. Muscle strength was measured using a handgrip dynamometer. Computed tomography images at the third lumbar vertebra level were used to assess muscle quantity and quality by the measuring cross-sectional muscle area and mean muscle attenuation, respectively. Probable sarcopenia was defined by low muscle strength. Sarcopenia was diagnosed by additional low muscle quantity or quality. Clinical outcomes were obtained by prospective data collection and follow up. RESULTS: Probable sarcopenia was identified in 419 patients, including 285 patients with sarcopenia. Patients with sarcopenia had a higher incidence of postoperative complications, higher costs, longer length of postoperative hospital stay, and worse overall survival (OS) and disease-free survival (DFS) compared with patients with low muscle strength only. The multivariate logistic analysis showed that sarcopenia and hypoproteinemia were independent risk factors for postoperative complications in patients with probable sarcopenia. Moreover, multivariate Cox analyses showed that sarcopenia remained an independent risk factor for OS and DFS in patients with probable sarcopenia. CONCLUSIONS: The measurement of muscle quantity/quality has additional predictive value for postoperative complications, OS, and DFS after gastrectomy for gastric cancer in patients with probable sarcopenia.

Influence of body composition, muscle strength, and physical performance on the postoperative complications and survival after radical gastrectomy for gastric cancer: A comprehensive analysis from a large-scale prospective study.

BACKGROUND: Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer. METHODS: A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery. RESULTS: There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI <25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients. CONCLUSION: There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival.

Impact of Body Composition and Physical Function on Quality of Life After Gastrectomy for Gastric Cancer.

PURPOSE: Patients with gastric cancer after gastrectomy often suffer from a decline in their quality of life (QoL), but the relationship between body composition (BC) and physical function on QoL has rarely been studied. This study aims to evaluate and determine the changes in QoL after gastrectomy and the impact of BC and physical function on QoL. METHODS: A total of 311 gastric cancer patients completed EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires before and 1, 3, 6 months post-surgery. Data including BC, handgrip strength (HGS) and 6-m gait speed (GS) were collected prospectively. Multiple linear regression analysis was used to determine the correlation between QoL and BC, HGS and GS. RESULTS: Patients had significantly worse scores after surgery on most function and symptom scales (p < 0.001), but most of these scales recovered within 6 months after surgery. A higher subcutaneous fat area (SFA)was associated with increased symptom scores 1 month after surgery. A higher GS is associated with a better global health status symptom. CONCLUSION: Patients suffer from a decline in their QoL after gastrectomy for gastric cancer. Intervention strategies aiming at reducing SFA and improving GS may improve the QoL in patients underwent gastrectomy for gastric cancer.

Highly Stretchable and Wearable Strain Sensor Based on Printable Carbon Nanotube Layers/Polydimethylsiloxane Composites with Adjustable Sensitivity.

Strain sensors that are capable of monitoring complex human motions with high accuracy are highly desirable for developing wearable electronics. This paper reports the fabrication of highly stretchable and sensitive multidirectional strain sensors with tunable strain gauge factors by employing a digitally controlled printer to incorporate carbon nanotube (CNT) layers into polydimethylsiloxane (PDMS) substrates. The fabricated sensors exhibit a high stretchability (up to 45%) and sensitivity with a gauge factor of 35.75. The gauge factors could be easily modulated by tuning the number of CNT printing cycles to accommodate diverse requirements. The cyclic loading-unloading test results revealed that the composite strain sensors exhibited excellent long-term durability. Particularly, in this work, for the first time, human-motion-induced strain was measured by a motion capture system and compared with the strain data obtained from the fabricated strain sensors. The deviation of strains measured by composite sensors is less than 20%, indicating the great accuracy of CNT/PDMS sensors to quantify the amount of motion-induced strain. Of significant importance is that due to the flexibility of the printing technique used, rosette-type sensors were fabricated to simultaneously measure strains along multiple axes. These superior sensing capabilities of the fabricated CNT/PDMS strain sensors give them great application potential in motion-detecting systems.