HPS6 Deficiency Leads to Reduced Vacuolar-Type H+-ATPase and Impaired Biogenesis of Lamellar Bodies in Alveolar Type II Cells.

Lamellar bodies (LBs) are tissue-specific lysosome-related organelles in type II alveolar cells that are the main site for the synthesis, storage, and secretion of pulmonary surfactants. Defects in pulmonary surfactants lead to a variety of respiratory and immune-related disorders. LB biogenesis is closely related to their function, but the underlying regulatory mechanism is largely unclear. Here, we found that deficiency of HPS6, a subunit of BLOC-2 (biogenesis of lysosome-related organelles complex-2), led to a reduction of the steady-state concentration of vacuolar-type H+-ATPase and an increase in the luminal pH of LBs. Furthermore, we observed increased LB size, accumulated surfactant proteins, and altered lipid profiling of lung tissue and BAL fluid due to HPS6 deficiency. These findings suggest that HPS6 regulates the distribution of vacuolar-type H+-ATPase on LBs to maintain its luminal acidity and LB homeostasis. This may provide new insights into the LB pathology.

Effects of IFN-γ on the immunological microenvironment and TAM polarity in stage IA non-small cell lung cancer and its mechanisms.

OBJECTIVE: To investigate the effect of interferon-γ (IFN-γ) on the immune microenvironment and the polarity of tumor-associated macrophages (TAMs) in stage IA non-small cell lung cancer (NSCLC) and its mechanisms. METHODS: Human non-small cell lung cancer A549 cells were treated with a series of IFN-γ concentrations (0, 50, 100, 150, 200, 250, and 300 ng/mL). Tumor tissues from patients with stage IA NSCLC were cultured using the air-liquid interface culture technique to establish a tumor microenvironment (TME) organ model. The NSCLC model was constructed by subcutaneously embedding small tumor pieces into the back of nonobese diabetic severe combined immune deficiency (NOD SCID) mice. The size and weight of the tumors were recorded, and the tumor volume was calculated. CCK-8 assays were used to investigate cell proliferation, flow cytometry and TUNEL staining were used to evaluate cell apoptosis, colony formation was investigated by cloning experiments, and cell invasion and migration were evaluated by Transwell assays and scratch tests. The expression of apoptosis-related proteins (Bax, Bcl-2 and C-caspase 3), M2 polarization-related markers (CD163, CD206 and IDO1), and marker proteins of cytotoxic T cells and helper T cells (CD8 and CD4) was detected by Western blot. The expression of Ki-67 and IDO1 was detected by immunohistochemistry, and the levels of IL-6, IL-10, IL-13 and TNF-α were measured by ELISA. The expression of CD68 was measured by RT‒qPCR, and the phagocytosis of TAMs was evaluated by a Cell Trace CFSE kit and cell probe staining. RESULTS: The proliferation activity of A549 cells increased with increasing IFN-γ concentration and peaked when the concentration reached 200 ng/mL, and the proliferation activity of A549 cells was suppressed thereafter. After treatment with 200 ng/mL IFN-γ, the apoptosis rate of cells decreased, the number of cell colonies increased, the invasion and migration of cells were promoted, the expression of Bax and C-caspase 3 was downregulated, and the expression of Bcl-2 was upregulated in cells and the TME model. In the TME model, CD163, CD206, IDO1 and Ki-67 were upregulated, CD8 and CD4 were downregulated, apoptosis was reduced, the levels of IL-6 and TNF-α were decreased, and the levels of IL-10 and IL-13 were increased. IL-4 induced TAMs to express CD163 and CD206, reduced the levels of IL-6 and TNF-α, increased the levels of IL-10 and IL-13, and weakened the phagocytic function of TAMs. IFN-γ treatment further enhanced the effect of IL-4 and enhanced the viability of A549 cells. IDO1 decreased the viability of T cells and NK cells, while suppressing the effect of IFN-γ. In mice, compared with NSCLC mice, the tumor volume and weight of the IFN-γ group were increased, the expression of CD163, CD206, IDO1, Ki-67 and Bcl-2 in tumor tissue was upregulated, the expression of Bax and C-caspase 3 was downregulated, and apoptosis was reduced. The levels of IL-6 and TNF-α were decreased, and the levels of IL-10 and IL-13 were increased in the serum of mice. CONCLUSION: In stage IA NSCLC, a low concentration of IFN-γ promotes the polarization of TAMs to the M2 phenotype in the TME model by upregulating the expression of IDO1, promoting the viability of cancer cells, inhibiting the viability of T cells and NK cells, and thus establishing an immune microenvironment conducive to tumor progression.

Electroacupuncture at Baliao point alleviates post-operative pain and anal distension after procedure for prolapse and hemorrhoids (stapled hemorrhoidopexy): a prospective randomized clinical trial.

PURPOSE: The purpose of this study was to explore the effect of electroacupuncture (EA) at Baliao point on short-term complications, such as anal pain and swelling, after procedure for prolapse and hemorrhoids (PPH) in patients with mixed hemorrhoids. METHODS: A total of 124 eligible patients undergoing PPH surgery were included in this study and randomly divided into a control group (n = 67) and an EA group (n = 57), with patients in the control group receiving only PPH surgery and patients in the EA group receiving PPH surgery and EA at Baliao point. RESULTS: The visual analogue scale (VAS) scores of EA group at 8, 24, 48, and 72 h after operation were significantly lower than those of control group. The anal distension scores at 8, 48, and 72 h after operation were also significantly lower than those of control group. The number of postoperative analgesic drug administration per patient was also significantly lower in the EA group. The incidence of urinary retention and tenesmus in EA group was significantly lower than that in control group within the first day after surgery. CONCLUSION: EA treatment at the Baliao point can alleviate short-term anal pain and anal swelling after the procedure for prolapse and hemorrhoids, reduce the incidence of urinary retention, and decrease the use of postoperative analgesic drugs. TRIAL REGISTRATION: This study was approved and registered by the Chinese Clinical Trial Center, Registration number: ChiCTR2100043519, Registration time: February 21, 2021 ( https://www.chictr.org.cn/ ).

Effect of Q-Box size on liver stiffness measurement by two-dimensional shear wave elastography.

PURPOSE: To investigate the effect of the Q-Box size on liver stiffness (LS) measurement by two-dimensional shear wave elastography (2D SWE). METHODS: Ninety-eight patients with chronic liver disease were enrolled. Each patient was continuously measured five times. The Q-Box diameter was adjusted to 10, 20, and 30 mm each time. The liver stiffness values (LSVs) at different diameters were compared in the following groups: LSVs ≤6.2 kPa, 6.2 kPa < LSVs ≤11 kPa, LSVs >11 kPa. The reliability and repeatability of LS measurement at different diameters were evaluated. RESULTS: The differences in LSVs at different Q-Box diameters were statistically significant only when LSV ≤6.2 kPa (p = 0.004). There were no statistically significant differences in standard deviation (SD), SD/median, coefficient of variation (CV), and interquartile range (IQR)/median at different Q-Box diameters (p > 0.05). There were statistical differences in minimum LSVs and percentage of minimum LSVs ≤0.2 kPa as well as in stability index (SI) and percentage of SI <90% at different Q-Box diameters (p < 0.05). The intraclass correlation coefficients (ICCs) were up to 0.98 at Q-Box diameters of 10, 20, and 30 mm. CONCLUSIONS: Our study showed that Q-Box size may lead to significant differences in LSVs, especially when LSVs ≤6.2 kPa. The Q-Box size had a large effect on the reliability of a single LS measurement but did not affect the repeatability of multiple measurements.

Prediction of harmful algal blooms in large water bodies using the combined EFDC and LSTM models.

Harmful algal blooms (HABs) is a worldwide water environmental problem. HABs usually happens in short time and is difficult to be controlled. Early warning of HABs using data-driven models is prospective in making time for taking precaution against HABs. High-frequency water quality monitoring data are necessary to improve the reliability of the model, but it is expensive. This research used environmental fluid dynamics code (EFDC) to extend one-point data obtained by only one instrument to the whole 249 ha water area instead of multi-instruments monitoring, followed by Long short-term memory (LSTM) to predict the HABs in the whole water body. Correlation analysis and principal component analysis were used to reduce the data dimension and improve model accuracy. Finally, the LSTM model was calibrated to predict chlorophyll-a (Chl-a) for the next 1 to 3 time steps. The Nash-Sutcliffe efficiency coefficient (NSE) and mean absolute percentage error (MAPE) of EFDC-LSTM were 0.797-0.991 and 2.74-13.16%, respectively, suggesting the promising utilization of this model in early warning systems for HABs. EFDC-LSTM achieves high-precision HABs forecasting in a cost-effective manner, providing a reliable way to detect HABs in advance.

Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment.

Reactive oxygen species (ROS) are rapidly eliminated and reproduced in organisms, and they always play important roles in various biological functions and abnormal pathological processes. Evaluated ROS have frequently been observed in various cancers to activate multiple pro-tumorigenic signaling pathways and induce the survival and proliferation of cancer cells. Hydrogen peroxide (H2O2) and superoxide anion (O2•-) are the most important redox signaling agents in cancer cells, the homeostasis of which is maintained by dozens of growth factors, cytokines, and antioxidant enzymes. Therefore, antioxidant enzymes tend to have higher activity levels to maintain the homeostasis of ROS in cancer cells. Effective intervention in the ROS homeostasis of cancer cells by chelating agents or metal complexes has already developed into an important anti-cancer strategy. We can inhibit the activity of antioxidant enzymes using chelators or metal complexes; on the other hand, we can also use metal complexes to directly regulate the level of ROS in cancer cells via mitochondria. In this review, metal complexes or chelators with ROS regulation capacity and with anti-cancer applications are collectively and comprehensively analyzed, which is beneficial for the development of the next generation of inorganic anti-cancer drugs based on ROS regulation. We expect that this review will provide a new perspective to develop novel inorganic reagents for killing cancer cells and, further, as candidates or clinical drugs.

Effectiveness of concomitant use of green tea and polyethylene glycol in bowel preparation for colonoscopy: a randomized controlled study.

BACKGROUND: Polyethylene glycol solution (PEG) is widely used for bowel preparation prior to colonoscopies. However, patients often exhibited adverse events as nausea, vomit and distention due to its uncomfortable tastes and potential side affects. This study aimed to evaluate the effectiveness and safety of concomitant use of green tea (GT) with PEG in bowel preparation prior to colonoscopy. METHODS: This was a prospective, randomized controlled study. It was conducted at an outpatient setting of colorectal surgery in a tertiary hospital. Patients aged 18 through 80 who were scheduled to undergo colonoscopy between August 2015 and February 2016 were randomly assigned into two groups, admitting either 2 L-PEG solutions with 1 L GT liquids or 2 L-PEG solutions only for bowel preparation. Admitted doses of PEG solutions, taste evaluation, adverse reactions (nausea and vomiting, distention and abdominal pain) were investigated by questionnaires. The bowel cleanliness of each patient was evaluated according to the Aronchick indicators. RESULTS: A total of 116 patients were enrolled in this study (PEG+GT 59, PEG 57). Full compliances were achieved in 93.2% patients of group PEG+GT and 59.6% of group PEG (p < 0.001). Mean Aronchick scale between two groups were 2.0 ± 0.9 versus 2.2 ± 0.7 respectively (PEG+GT vs PEG, p = 0.296). Rates of adverse events as nausea and vomiting, abdominal pain in bowel preparation were significantly different between two groups (55.9% vs 77.2%, p = 0.015 and 13.6% vs 33.3%, p = 0.012). Patients in group PEG+GT who have probabilities to receive repeating colonoscopy had a higher willingness to accept PEG+GT again for bowel preparation, compared with PEG group (94.9% vs 57.9%, p < 0.001). CONCLUSIONS: Concomitant use of green tea and polyethylene glycol may effectively reduce incidence of adverse events, increase compliances, with comparable bowel cleanliness in bowel preparation. TRIAL REGISTRATION: This trial was retrospectively registered on Feb 1st, 2019 (ChiCTR1900021178).

Does Operator Experience and the Q-Box Diameter Affect the Repeatability of Liver Stiffness Measurements Obtained by 2-Dimensional Shear Wave Elastography?

OBJECTIVES: The purpose of this research was to evaluate whether operator experience and the quantitative analysis system (Q-Box; SuperSonic Imagine, Aix-en-Provence, France) diameter affect the repeatability of liver stiffness measurements. METHODS: We enrolled 417 outpatients. All measurements were performed by 2 operators, including an expert and a novice. Each patient was continuously measured 3 times by the 2 operators. The Q-Box diameter was adjusted to 10, 20, and 30 mm each time, and the mean elasticity values were recorded. Intraobserver repeatability was evaluated by the intraclass correlation coefficient (ICC). Interobserver repeatability was evaluated by the ICC, coefficient of variation (CV), and Bland-Altman plots. RESULTS: The study group included 241 male and 176 female patients. The expert operator had higher ICCs than the novice operator at each Q-Box diameter. The overall interobserver agreement was excellent, and the results showed that compared to other groups, the ICC was the lowest and the CV was the largest for the 30-mm-diameter group. The ICC and CV values were similar between the 10- and 20 mm-diameter groups. The Bland-Altman plots showed that the mean difference was -0.2 kPa for the 10-, 20-, and 30 mm-diameter groups. However, the limits of agreement were the largest in the 30-mm-diameter group and were similar between the 10- and 20-mm-diameter groups. CONCLUSIONS: The repeatability of liver stiffness measurements is affected not only by experience but also by the Q-Box diameter.

Elevated G-Protein Receptor 125 (GPR125) Expression Predicts Good Outcomes in Colorectal Cancer and Inhibits Wnt/ß-Catenin Signaling Pathway.

BACKGROUND G-protein receptor 125 (GPR125), as a transmembrane signal transducer, is involved in regulating cancer development. Although GPR125 is related with several cancers, its role in colorectal cancer (CRC) and the underlying mechanism are still unknown. Here, we investigated the clinical significance of GPR125 in CRC. MATERIAL AND METHODS We assessed the expression level of GPR125 in CRC tissues by analyzing 3 datasets in the Gene Expression Omnibus (GEO) database and in human samples. The correlation between GPR125 expression and clinicopathological features was further analyzed. Survival analysis was performed to assess the association between GPR125 expression and recurrence-free survival (RFS). Cox logistic regression analysis was used to analyze the role of GPR125 expression in overall survival (OS). Moreover, we activated the Wnt pathway in HCT116 cells to investigate their potential mechanism. RESULTS Analysis of the GEO database showed that the expression of GPR125 was down-regulated in CRC tissues, consistent with our human samples experiments, and patients with higher GPR125 expression had a longer RFS. Also, we found that high GPR125 expression was associated with better tumor outcomes in clinical stage, metastasis, and KRAS status. Cox logistic regression analysis demonstrated that GPR125 was an independent prognostic factor for favorable outcome. Mechanistically, GPR125 overexpression inhibited the ß-catenin transcriptional activity, and down-regulated the expression levels of the Wnt downstream proteins-Axin2, c-Myc, cylinD1, and lef-1. CONCLUSIONS GPR125 may be a potential prognosis-related anti-oncogene and its effects on inactivating Wnt/ß-catenin signaling pathway might be a key link to inhibiting CRC formation.

Preparation and Effect of CO2 Response Gel for Plugging Low-Permeability Reservoirs.

In order to solve the problem of gas channeling during CO2 flooding in low-permeability reservoirs, a novel CO2 responsive gel channeling system was prepared by using carrageenan, branched polyethylene imide and ethylenediamine under laboratory conditions. Based on the Box-Behnken response surface design method, the optimal synthesis concentration of the system was 0.5 wt% carrageenan, 2.5 wt% branchized polyethylenimide and 6.5 wt% ethylenediamine. The micromorphology of the system before and after response was characterized by scanning electron microscopy. The rheology and dehydration rate were tested under different conditions. The channeling performance and enhanced oil recovery effect of the gel system were simulated by a core displacement experiment. The experimental results show that the internal structure of the system changes from a disordered, smooth and loosely separated lamellae structure to a more uniform, complete and orderly three-dimensional network structure after exposure to CO2. The viscosity of the system was similar to aqueous solution before contact with CO2 and showed viscoelastic solid properties after contact with CO2. The experiment employing dehydration rates at different temperatures showed that the internal structure of the gel would change at a high temperature, but the gel system had a certain self-healing ability. The results of the displacement experiment show that the plugging rate of the gel system is stable at 85.32% after CO2 contact, and the recovery rate is increased by 17.06%, which provides an important guide for the development of low-permeability reservoirs.

Numerical Modeling of Foam Carrying Sand Transport in Multifactor Horizontal Wells.

The solution of wellbore multiphase flow models has an important position in oil-gas field development. However, the solution of multiphase flow models often involves a series of complicated situations such as interphase mass and energy transfer, surface problems, and so on. Foam carrying sand particles in the wellbore is a solid, liquid, and gas three-phase cylinder flow problem. To solve this problem, we developed a computational fluid dynamics-discrete element method model based on the traditional N-S equations to track the streamline of the foam fluid and sand particles in the wellbore. On this basis, we investigated the influence of three factors, i.e., foam and sand properties and wellbore parameters, on the sand carrying rate of foam. The results show that whether the sand mound at the bottom of wells that can be dispersed is mainly affected by the properties of foam. The location of sand deposition in the wellbore and the effectiveness of foam in sand transportation are mainly influenced by the wellbore parameters and sand properties.

Clinical and molecular heterogeneity associated with tumor sidedness in colorectal liver metastasis: a multicenter propensity cohort study.

Background: Colorectal liver metastasis (CRLM) exhibits highly heterogeneity, with clinically and molecularly defined subgroups that differ in their prognosis. The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM. Methods: This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1, 2012, to December 31, 2020. Propensity score matching with 1:1 ratio matching was performed. The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status. Moreover, whole-exome sequencing (WES) of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles. Results: The median follow-up was 68 months. Matching yielded 481 pairs of patients. Compared to right-sided CRLM, left-sided patients experienced with better 5-year overall survival (OS) in surgery responsiveness, with a 14.6 lower risk of death [hazard ratio (HR), 1.36, 95% confidence interval (CI), 1.10-1.69, P=0.004]. Interaction between tumor sidedness and KRAS status was statistically significant: left-sidedness was associated with better prognosis among KRAS wild-type patients (HR 1.71; 95% CI: 1.20-2.45; P=0.003), but not among KRAS mutated-type patients. Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53, APC, KRAS, and BRAF alterations, and identified a critical role of KRAS mutation in correlation with their survival differences. Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors (29.3% vs. 15.5%, P=0.03). Conclusions: We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors. Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.

Application of the intestine diversion tube with a double-balloon without ileostomy in low rectal cancer.

Background: Ileostomy is often used in low rectal cancer to protect the anastomosis and reduce the incidence of anastomotic leakage. However, the closure of the stoma causes physical and psychological damage to patients. An intestine diversion tube with a double-balloon was designed to remove the need for ileostomy and a secondary surgery, and we sought to verify its effectiveness and safety. Methods: An intestine diversion tube with a double-balloon was designed, and the experiment was performed in 5 groups of experiment pigs by the same group of physicians. The tube was placed into the ileum through the cecum during surgery. All the animals were anatomized after being anesthetized on the 14th day postoperatively to check the anastomosis and abdominal cavity. The postoperative complications included anastomotic leakage, abdominal or pelvic infection, anastomotic stenosis, postoperative bleeding, intestinal obstruction, reoperation, electrolyte disorder, drainage tube blockage, and drainage tube fall off. Results: No serious postoperative complications occurred in the 5 animal groups. The average daily drainage tube volume was 188.6 mL, the average drainage tube removal time was 13.4 days, and the average first defecation time was 2.6 days. Postoperative drainage was smooth, and no anastomotic leakage, other complications, or animal deaths occurred. Conclusions: The use of the intestine diversion tube with a double-balloon was feasible in animal experiments and was safe and effective. The procedure is simple, and suitable for popularization and application in the clinic.

Artifacts in two-dimensional shear wave elastography of liver.

BACKGROUND: Artifacts are common when using two-dimensional shear wave elastography (2-D SWE) to measure liver stiffness (LS), but they are poorly recognized. AIM: To investigate the presence and influence of artifacts in 2-D SWE of liver. METHODS: We included 158 patients with chronic liver disease, who underwent 2-D SWE examination by a novice and an expert. A cross line at the center of the elastogram was drawn and was divided it into four locations: top-left, top-right, bottom-left, and bottom-right. The occurrence frequency of artifacts in different locations was compared. The influence of artifacts on the LS measurements was evaluated by comparing the elastogram with the most artifacts (EMA) and the elastogram with the least artifacts (ELA). RESULTS: The percentage of elastograms with artifacts in the novice (51.7%) was significantly higher than that of the expert (19.6%) (P < 0.001). It was found that both operators had the highest frequency of artifacts at bottom-left, followed by top-left and bottom-right, and top-right had the lowest frequency. The LS values (LSVs) and standard deviation values of EMAs were significantly higher than those of ELAs for both operators. An intraclass correlation coefficient value of 0.96 was found in the LSVs of EMAs of the two operators, and it increased to 0.98 when the LSVs of the ELAs were used. Both operators had lower stability index values for EMAs than ELAs, but the difference was only statistically significant for the novice. CONCLUSION: Artifacts are common when using 2-D SWE to measure LS, especially for the novice. Artifacts may lead to the overestimation of LS and reduce the repeatability and reliability of LS measurements.

Rapid Fabrication of Flexible Cu@Ag Flake/SAE Composites with Exceptional EMIS and Joule Heating Performance.

High electromagnetic interference shielding (EMIS) effectiveness and good thermal management properties are both required to meet the rapid development of integrated electronic components. However, it remains challenging to obtain environmentally friendly and flexible films with high EMIS and thermal management performance in an efficient and scalable way. In this paper, an environmentally friendly strategy is proposed to synthesize multifunctional waterborne Cu@Ag flake conductive films using water as the solvent and silicone-acrylic emulsion (SAE) as a matrix. The obtained films show high electrical conductivity and exceptional EMI SE and electrothermal conversion properties. The EMI SE in the X-band is higher than 76.31 dB at a thickness of 60 µm owing to the ultrahigh electrical conductivity of 1073.61 S cm-1. The film warms up quickly to 102.1 °C within 10 s under a low voltage of 2.0 V. In addition, the shielding coating is sufficiently flexible to retain a conductivity of 93.4% after 2000 bending-release cycles with a bending radius of 3 mm. This work presents an alternative strategy to produce high EMIS effectiveness and Joule heating films for highly integrated and flexible electronic components in a green, scalable, and highly efficient way.

Clinical study on risk factors related to postoperative recurrence or metastasis of rectal cancer: a retrospective cohort study.

Background: Rectal cancer is usually treated by surgery, but recurrence or metastasis seriously affect the quality of life and survival of patients. Identifying the risk factors for postoperative recurrence or metastasis of rectal cancer has important guiding value for the treatment of rectal cancer. However, the research on risk factors of postoperative recurrence or metastasis of rectal cancer has not been unified. Methods: The data of all patients undergoing rectal cancer surgery in The Fifth People's Hospital of Shanghai, Fudan University, from 2016 to 2020 were collected and analyzed. A total of 185 patients were included for statistical analysis and were divided into a recurrence or metastasis group and a non-recurrence or metastasis group. Patients were followed up according to National Comprehensive Cancer Network (NCCN) guidelines by enhanced CT or MRI, and colonoscopy. The cut-off of the research was recurrence, metastasis, or death. Logistic regression analysis and Cox regression analysis were used to analyze the risk factors related to postoperative recurrence or metastasis of rectal cancer, and the survival curve was drawn. Results: Multiple logistic regression analysis showed involvement of the mesorectal fascia (MRF) [OR (odds ratio) =2.9, 95% confidence interval (CI): 1.16-7.29, P=0.023], nerve and vascular invasion (OR =1.7, 95% CI: 1.08-2.59, P=0.022), intraoperative blood transfusion (OR =3.7, 95% CI: 1.45-9.40, P=0.006), and Dukes staging (OR =2.3, 95% CI: 1.26-4.35, P=0.007) were independent risk factors for postoperative recurrence or metastasis of rectal cancer. Involvement of mesenteric fascia infiltration (OR =11.5, 95% CI: 1.49-88.79, P=0.019) and Dukes stage (OR =3.0, 95% CI: 1.46-6.26, P=0.003) were independent risk factors for liver metastasis, while nerve and vascular invasion (OR =2.4, 95% CI: 1.19-5.00, P=0.015) was an independent risk factor for pulmonary metastasis. Conclusions: Postoperative recurrence or metastasis of rectal cancer is related to many factors. These findings have clinical guiding value and significance for the follow up and prognosis of patients with rectal cancer after surgery. Large-scale prospective clinical studies are needed.

Association of Simultaneous vs Delayed Resection of Liver Metastasis With Complications and Survival Among Adults With Colorectal Cancer.

Importance: Simultaneous or delayed resection of synchronous liver metastasis (SLM) with primary colorectal cancer (CRC) remains a controversial topic. Objective: To investigate the outcomes of simultaneous vs delayed resection in patients with resectable SLM. Design, Setting, and Participants: This comparative effectiveness research study included 1569 patients with resectable SLM who underwent curative-intent liver resection at 3 independent centers in China between January 1, 2000, to December 31, 2019. A 1:1 propensity score matching was performed. Follow-up was completed on August 31, 2021, and the data were analyzed from April 1 to 30, 2022. Main Outcomes and Measures: Primary outcome was the percentage of patients with at least 1 major complication within 60 days after surgery. Secondary outcomes were intraoperative and postoperative complications, overall survival (OS), and cancer-specific survival (CSS) rates. Results: Among the 1569 patients included, 1057 (67.4%) underwent delayed resection (719 men [68.0%] with a mean [SD] age of 57.4 [11.2] years), and 512 patients (310 men [60.5%] with a mean [SD] age of 57.1 [10.5] years) underwent simultaneous resection. Matching yielded 495 pairs of patients underwent simultaneous resection. The percentage of major perioperative complications did not differ between the simultaneous and delayed resection groups (34.1% vs 30.0%; P = .89). The OS rates were 65.2% at 3 years, 47.1% at 5 years, and 38.0% at 8 years for the delayed resection group and 78.0% at 3 years, 65.4% at 5 years, and 63.1% at 8 years for the simultaneous resection group (hazard ratio [HR], 1.42; 95% CI, 1.10-1.85, P = .003). The CSS rates were 68.3% at 3 years, 48.5% at 5 years, and 37.1% at 8 years for the delayed resection group and 79.2% at 3 years, 67.2% at 5 years, and 65.9% at 8 years for the simultaneous resection group (HR, 1.45; 95% CI, 1.14-1.98; P = .004). On subgroup analysis comparing the 2 strategies according to the KRAS sequence variation status, the OS rates (HR, 1.61; 95% CI, 1.45-2.18; P < .001) and CSS rates (HR, 1.62; 95 CI, 1.40-1.87; P = .003]) in the simultaneous resection group were significantly better than those in the delayed resection group in patients with KRAS wild-type tumors. Conclusions and Relevance: Results of this study suggest that complication rates did not differ when CRC and SLM were resected simultaneously and that the survival benefits of simultaneous resection were restricted to patients with KRAS wild-type tumors. Integrating molecular features into the treatment decision is a basis for accurate, individualized treatments.

Copper-thiosemicarbazone complexes conjugated-cellulose fibers: Biodegradable materials with antibacterial capacity.

Personal protective equipment (PPE) is vital in battling bacteria crisis, but conventional PPE materials lack antimicrobial activities and environmental friendliness. Our work focused on developing biodegradable and antibacterial fibers as promising bioprotective materials. Here, we grafted highly effective antibacterial copper-thiosemicarbazone complexes (CT1-4) on cellulose fibers via covalent linkages. Multiple methods were used to characterize the chemical composition or morphology of CT1-4 conjugated-fibers. Conjugation of CT1-4 maintains the mechanical properties (Breaking strength: 2.35-2.45 cN/dtex, Breaking elongation: 7.19 %-7.42 %) and thermal stability of fibers. CT1 can endow cellulose fibers with the excellent growth inhibition towards Escherichia coli (E. coli) (GIR: 61.5 % ± 1.28 %), Staphylococcus aureus (S. aureus) (GIR: 85.7 % ± 1.93 %), and Bacillus subtilis (B. subtilis) (GIR: 87.6 % ± 1.44 %). We believe that the application of CT1 conjugated-cellulose fibers is not limited to the high-performance PPE, and also can be extended to various types of protective equipment for food and medicine safety.

Stress Evaluation of Welded Joints with Metal Magnetic Memory Testing Based on Tension-Compression Fatigue Test.

Metal magnetic memory testing (MMMT) is an effective nondestructive technique for fatigue damage monitoring of weldments because of its capacity for stress evaluation. An experimental investigation of the effect of the applied fatigue stress on MMMT signals, including the tangential component Bx and the normal component Bz, during tension-compression fatigue tests in welded joints was carried out systematically. The Bx and Bz signals at different fatigue cycles and fatigue stresses were collected and analyzed, and the results showed that there was a peak of Bx and abnormal peaks of Bz that existed at the welded joint before loading. After loading, the peak of Bx and the abnormal peaks of Bz reversed, and the Bx signals moved upward and the Bz signals rotated anticlockwise dramatically in the first few fatigue cycles. After the fatigue cycle number was larger than 1000, Bx and Bz were stable, with very little fluctuation. In addition, the characteristics of Bx signals, the mean value, and the peak value of the average of Bx had an extremely significant linear relationship with the applied fatigue stress during the stable stage of the fatigue test, which indicates that MMMT is a feasible method for fatigue stress evaluation and even residual fatigue life estimation for weldments in service.

Long non-coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2-mediated epigenetic modification.

Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine-resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine-resistant PC cells (PANC-1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild-type PC cells and in gemcitabine-resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p-Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation-quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p-Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2-mediated epigenetic modification.