The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity.

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.

Initial experience of visualized biliary cannulation during ERCP.

BACKGROUND : Selective biliary cannulation is the most challenging step in endoscopic retrograde cholangiopancreatography (ERCP) because only indirect radiographic images can be obtained. Therefore, we developed a novel endoscopic retrograde direct cholangioscopy (ERDC) technology to facilitate visible biliary cannulation. METHODS : In this case series, we used ERDC to treat 21 patients with common bile duct stones who were enrolled consecutively between July 2022 and December 2022. The procedure details and complications were recorded, and all patients were followed up for 3 months after the procedure. The learning curve effect was analyzed by comparing the early and later cases. RESULTS : Biliary cannulation was successful in all patients, and the stones were removed completely. The median (interquartile range [IQR]) time for cholangioscopy-guided biliary cannulation was 240.0 (10.0-430.0) seconds, and the median (IQR) number of cannulation procedures was 2 (1-5). Despite there being one episode of post-ERCP pancreatitis, one of cholangitis, and three patients developing asymptomatic hyperamylasemia, all of the patients recovered after symptomatic treatment, being discharged and with no serious adverse events occurring during the 3-month follow-up period. Compared with the early cases, the number of intubations and the use of guidewire guidance decreased in later cases. CONCLUSION : Our research confirms that ERDC is a feasible technology for biliary cannulation under direct vision.

Artificial intelligence empowers the second-observer strategy for colonoscopy: a randomized clinical trial.

Background: In colonoscopy screening for colorectal cancer, human vision limitations may lead to higher miss rate of lesions; artificial intelligence (AI) assistance has been demonstrated to improve polyp detection. However, there still lacks direct evidence to demonstrate whether AI is superior to trainees or experienced nurses as a second observer to increase adenoma detection during colonoscopy. In this study, we aimed to compare the effectiveness of assistance from AI and human observer during colonoscopy. Methods: A prospective multicenter randomized study was conducted from 2 September 2019 to 29 May 2020 at four endoscopy centers in China. Eligible patients were randomized to either computer-aided detection (CADe)-assisted group or observer-assisted group. The primary outcome was adenoma per colonoscopy (APC). Secondary outcomes included polyp per colonoscopy (PPC), adenoma detection rate (ADR), and polyp detection rate (PDR). We compared continuous variables and categorical variables by using R studio (version 3.4.4). Results: A total of 1,261 (636 in the CADe-assisted group and 625 in the observer-assisted group) eligible patients were analysed. APC (0.42 vs 0.35, P = 0.034), PPC (1.13 vs 0.81, P < 0.001), PDR (47.5% vs 37.4%, P < 0.001), ADR (25.8% vs 24.0%, P = 0.464), the number of detected sessile polyps (683 vs 464, P < 0.001), and sessile adenomas (244 vs 182, P = 0.005) were significantly higher in the CADe-assisted group than in the observer-assisted group. False detections of the CADe system were lower than those of the human observer (122 vs 191, P < 0.001). Conclusions: Compared with the human observer, the CADe system may improve the clinical outcome of colonoscopy and reduce disturbance to routine practice (Chictr.org.cn No.: ChiCTR1900025235).

Perioperative Renin-Angiotensin System Inhibitors Improve Major Outcomes of Heart Failure Patients Undergoing Cardiac Surgery: A Propensity-Adjusted Cohort Study.

OBJECTIVE: The aim of this study was to study the association of perioperative administration of renin angiotensin system inhibitors (RASi) and clinical outcomes of patients with heart failure (HF) undergoing cardiac surgery. SUMMARY BACKGROUND DATA: It is controversial whether the perioperative RASi should be administered in HF patients undergoing cardiac surgery. METHODS: A total of 2338 patients with HF and undergoing CABG and/or valve surgeries at multiple hospitals from 2001 to 2015 were identified from STS database. After adjustment using propensity score and instrumental variable, logistic regression was conducted to analyze the influence of preoperative continuation of RASi (PreRASi) on short-term in-hospital outcomes. Independent risk factors of 30-day mortality, major adverse cardiovascular events (MACE), and renal failure were analyzed by use of stepwise logistic regression. The effects of pre- and postoperative use of RASi (PostRASi) on long-term mortality were analyzed using survival analyses. Stepwise Cox regression was conducted to analyze the independent risk factors of 6-year mortality. The relationships of HF status and surgery type with perioperative RASi, as well as PreRASi-PostRASi, were also evaluated by subgroup analyses. RESULTS: PreRASi was associated with lower incidences of 30-day mortality [ P < 0.0001, odds ratio (OR): 0.556, 95% confidence interval (CI) 0.405-0.763], stroke ( P =0.035, OR: 0.585, 95% CI: 0.355-0.962), renal failure ( P =0.007, OR: 0.663, 95% CI: 0.493-0.894). Both PreRASi ( P =0.0137) and PostRASi ( P =0.007) reduced 6-year mortality compared with the No-RASi groups. CONCLUSIONS: Pre- and postoperative use of RASi was associated with better outcomes for the patients who have HF and undergo CABG and/or valve surgeries. Preoperative continuation and postoperative restoration are warranted in these patients.

Serum CTRP9 and high-molecular weight adiponectin are associated with ischemic stroke.

BACKGROUND: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke. METHODS: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured. RESULTS: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke and increased during stage III (11th day to one month) and stage IV (1 month after), compared to control. In the non-hyperlipidemia group, serum CTRP9, tAPN, and HMW were decreased in ischemic stroke patients compared to control (P < 0.05). Serum CTRP9 is closely related to serum tAPN and HMW (r = 0.992, 0.991). Serum CTRP9 are protective against ischemic stroke (OR = 0.400, 95% CI 0.197-0.810, P < 0.05). CONCLUSIONS: Lower serum CTRP9, tAPN, LMW, and HMW are significantly associated with increased ischemic stroke risk in non-hyperlipidemia subjects. CTRP9, tAPN, and HMW isoforms may be valuable clinical indicators for patients with ischemic stroke.

Adjuvant treatment for patients with incidentally resected limited disease small cell lung cancer-a retrospective study.

Background: With the exception of very early-stage small cell lung cancer (SCLC), surgery is not typically recommended for this disease; however, incidental resection still occurs. After incidental resection, adjuvant salvage therapy is widely offered, but the evidence supporting its use is limited. This study aimed to explore proper adjuvant therapy for these incidentally resected SCLC cases. Methods: Patients incidentally diagnosed with SCLC after surgery at the Shanghai Pulmonary Hospital in China from January 2005 to December 2014 were included in this study. The primary outcome was overall survival. Patients were classified into different group according to the type of adjuvant therapy they received and stratified by their pathological lymph node status. Patients' survival was analyzed using a Kaplan-Meier analysis and Cox regression analysis. Results: A total of 161 patients were included in this study. Overall 5-year survival rate was 36.5%. For pathological N0 (pN0) cases (n=70), multivariable analysis revealed that adjuvant chemotherapy (ad-chemo) was associated with reduced risk of death [hazard ratio (HR): 0.373; 95% confidence interval (CI): 0.141-0.985, P=0.047] compared to omission of adjuvant therapy. For pathological N1 or N2 (pN1/2) cases (n=91), taking no adjuvant therapy cases as a reference, the multivariable analysis showed that ad-chemo was not associated with a lower risk of death (HR: 0.869; 95% CI: 0.459-1.645, P=0.666), while adjuvant chemo-radiotherapy (ad-CRT) was associated with a lower risk of death (HR: 0.279; 95% CI: 0.102-0.761, P=0.013). Conclusions: Patients who incidentally receive surgical resection and are diagnosed with limited disease SCLC after resection should be offered adjuvant therapy as a salvage treatment. For incidentally resected pN0 cases, ad-chemo should be considered and for pN1/2 cases, ad-CRT should be received.

Scale development of apparel customization brand value: From the perspectives of practitioners and consumers.

China apparel customization brands (CACBs) have been recently growing in massive quantities despite being in their infancy stages of brand value building. Although scholars have proven brand value's importance in sustainable brand growth, studies on the specific context of CACBs are still limited. This research proposes a conceptual framework of CACBs' brand value measured dimension based on previous studies and divides brand value into both general and specific dimensions. Accordingly, qualitative (semi-structured interviews) and quantitative (online survey) studies were conducted from the perspectives of practitioners and consumers. Ultimately, a scale of 30 items with nine dimensions was generated. Results reveal that brand association in the general dimensions and brand service in the special dimensions were the largest promoters of CACB brand value. Hence, practitioners should pay more attention to dimensions of cognitive conflicts. Practical suggestions for apparel customization marketers are proposed to build and enhance brand value.

Hyperlipidemic plasma molecules bind and inhibit adiponectin activity.

INTRODUCTION: Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. Here, we took an unbiased approach to identify whether hyperlipidemic plasma molecules exist that bind and inhibit adiponectin function, contributing to adiponectin resistance and diabetic vascular injury. METHODS: Adult rats were randomly assigned to receive either a normal or a high-fat diet for 8 weeks. Plasma was co-immunoprecipitated with anti-APN antibody and analyzed by mass spectrometry. The APN binding molecules and their effect upon APN biological activity were determined. RESULTS: As expected, the high-fat-diet increased plasma triglyceride, total cholesterol, and low-density lipoprotein. Importantly, the circulating APN level was significantly increased at this time point. Mass spectrometry identified 18 proteins with increased APN binding in hyperlipidemic plasma, among which four proteins critical in lipid metabolism, including apolipoprotein A1 (APOA1), APOA4, APOC1, and paraoxonase 1, were further investigated. Incubating recombinant APN with APOA1 markedly (P < 0.01), and incubating with APOC1 significantly (P < 0.05), inhibited APN activity as evidenced by the reduced AMPK activation in HUVECs. APOA4 and paraoxonase 1 incubation had no effect upon APN activity. Finally, plasma APOA1 was significantly increased (P < 0.05) in hyperlipidemic plasma compared with the control plasma. CONCLUSIONS: It was demonstrated for the first time that increased APOA1 and APOC1 in hyperlipidemic plasma binds and inhibits APN activity. This result not only identifies a novel molecular mechanism responsible for adiponectin resistance during early stage diabetes, but also provides additional new insight into the diverse/controversial (protective and harmful) functions of high-density lipoprotein.

Evaluating nitric oxide produced by rat inflamed microglial cell Lline, CHME-5, under the effect of IMOD.

Nitric oxide (NO), as a free radical, is produced by inflamed microglia cells and is one of the destructive factors of the immune system and a factor in myelin degradation. Therefore, inhibition of microglia activity is a chief strategy in reducing neurotoxic damage to the central nervous system. In this study, an herbal Immunomodulatory Drug (IMOD) was used to evaluate the effects of this drug in controlling the amount of nitric oxide. Nitric oxide induction was performed by bacterial lipopolysaccharide (LPS) in rat inflamed microglial cell line, CHME-5. ELISA test was used to measure the produced nitric oxide at 24, 48, and 72 hours. The results showed that the high concentrations of IMOD (1.2, and 4% V/V) had anti-inflammatory effects on microglial cells and were able to reduce the amount of nitric oxide in these cells but the effective dose of IMOD was in the range of 1.2% V/V. Therefore, the safest dose and the best time for the effect of IMOD on inflammatory cell groups are 1.2% V/V and 72h, respectively. Hence, with further studies, IMOD can be considered as an herbal anti-inflammatory drug that is effective in controlling neurodegenerative diseases.

Evaluation of Efficacy of Corticosteroid and Corticosteroid Combined with Botulinum Toxin Type A in the Treatment of Keloid and Hypertrophic Scars: A Meta-Analysis.

BACKGROUND: Both keloid and hypertrophic scars are common benign skin lesions manifested by hyperplasia of fibroblasts. Clinically, this will not only have physiological effects on patients, but also cause psychological damage. However, there is no unified standard treatment method at present. Intralesional corticosteroid injection alone and corticosteroid combined with botulinum toxin type A has been gradually found to be useful for the treatment of keloid and hypertrophic scars, but the difference in efficacy between the two is controversial. METHODS: A systematic search was made of the relevant experiments from Web of Science, PubMed, Scopus, Google Scholar, Cochrane Library, and China National Knowledge Infrastructure (CNKI). RESULTS: The scores of Visual Analog Scale (VAS), Vancouver Scar Score sheet (VSS), scar thickness, itching degree and patient satisfaction after the combination of corticosteroid and botulinum toxin type A were superior than those after corticosteroid (P<0.05). CONCLUSION: Compared with corticosteroid alone, corticosteroid combined with botulinum toxin type A is more effective in the treatment of keloid and hypertrophic scar. Although clinical case studies for the treatment of keloid or hypertrophic scars are limited, it is necessary and helpful to understand the effectiveness of corticosteroid combined with botulinum toxin type A in the treatment of keloid or hypertrophic scars. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Effects of fertilizer application on yield and fertilizer utilization of Coffea arabica in southwest dry-hot region of China under different shading levels]. / 不同遮荫条件下施肥量对西南干热区小粒咖啡产量和肥料利用的影响.

The fertilizer and shading management of Coffea arabica in dry-hot area is extensive, resulting in lower yield and fertilizer utilization efficiency. A field experiment was carried out to find the coupling mode of shading and fertilizer for fertilizer-saving and high yield of C. arabica in dry-hot region. Four shading levels (100% NR, 75% NR, 60% NR, 45% NR, NR was natural radiation) and four fertilizer levels (No fertilization and 666.67, 1000, 1333.33 kg·hm-2) were set to examine the effects of different radiations and fertilizer treatments on canopy structure, yield, ferti-lizer use efficiency, soil nutrient content and microbial biomass carbon of C. arabica. The results showed that canopy structure, yield, fertilizer use efficiency, soil nutrient content and microbial biomass carbon were significantly affected by shading and fertilizer treatments. Soil nutrient content and microbial biomass carbon decreased with the increases of shading levels. Soil nutrient content increased with the increases of fertilizer application, while microbial biomass carbon increased first and then decreased, with a peak at the rate of 1000 kg·hm-2(200.30 mg·kg-1). Shading and fertilizer had significant effects on the canopy structure including leaf area index and openness. There were significant negative correlations of leaf area index with openness, gap fraction, total fixed-point factor and total radiation under canopy. Results of response surface analysis and spatial analysis showed that the combination of shading level and fertilizer application were 80% NR and 666.67 kg·hm-2, 79% NR and 1286.81 kg·hm-2, 79% NR and 967.74 kg·hm-2, 82% NR and 1075.27 kg·hm-2, respectively, when partial fertilizer productivity, yield, fertilizer agronomic efficiency and yield increase of fertilizer reached the maximum. The ranges of shading and fertilizer were 68%-77% NR and 946.24-1178.79 kg·hm-2 when the yield, agronomic efficiency and yield increasing rate by fertilizer reached 80% of the maximum value. In this experiment, the optimum combination of shading level and fertilizer application was 75% NR and 1000 kg·hm-2.

Preventive Effects of Nicorandil Against Contrast-Induced Nephropathy in Patients With Moderate Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

We investigated the preventive effect of nicorandil on contrast-induced nephropathy (CIN) in patients with moderate renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 250 patients with a creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to either a nicorandil group (nicorandil 10 mg 3 times/d and hydration; n = 125) or a control group (hydration only; n = 125). The first end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or ≥25% within 72 hours after exposure to the contrast medium. The secondary end points were (1) changes in Scr, blood urea nitrogen, and crCl and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 1.6% (2/125) in the nicorandil group and 9.6% (12/125) in the control group (P = .011). There was no obvious difference in the incidence of major adverse events during hospitalization between the nicorandil and the control group (4.0% vs 4.8%, P = 1.000). Multivariate logistic regression analysis showed that nicorandil was a protective factor for CIN (odds ratios = 0.126, 95% confidence interval: -19.996 to -0.932, P = .012). Prophylactic administration of nicorandil may prevent against CIN in patients with moderate renal insufficiency undergoing PCI.

Consensus on the digestive endoscopic tunnel technique.

With the digestive endoscopic tunnel technique (DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria (MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal (GI) tract. At present, the tunnel technique application range covers the following: (1) Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis; (2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and (3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment. The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism, and significance of DETT, prevention of infection and concepts of DETT-associated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract (indications and contraindications, procedures, pre- and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

The good, the bad, and the ugly of calcium supplementation: a review of calcium intake on human health.

Calcium is an important integrative component of the human body and critical for human health. It has been well established that calcium intake is helpful in the prevention and treatment of osteoporosis, which has become one of the most serious public health problems across the world. However, community-dwelling adults with and without osteoporosis are rarely concerned or even not aware of the potential side effects of high or inappropriate doses of calcium intake. Some recent studies have revealed that excessive calcium intake might increase the risks of cardiovascular diseases. The purpose of this article was to review the health benefits, costs, and consequences of calcium supplementation on osteoporosis/osteoporotic fractures, cardiovascular events, kidney stones, gastrointestinal diseases, and other important diseases. In the end, we suggest that calcium supplementation should be prescribed and taken cautiously, accounting for individual patients' risks and benefits. Clearly, further studies are needed to examine the health effects of calcium supplementation to make any solid recommendations for people of different genders, ages, and ethnicities.