Personalizing age of gastric cancer screening based on comorbidity in China: Model estimates of benefits, affordability and cost-effectiveness optimization.

The benefits of gastric cancer screening are related to age and comorbidity status, but reliable estimates are lacking in China. This study aimed to estimate the benefits and affordability of the gastric cancer screening strategy by level of comorbidity to inform decisions to screening age. We assessed six current gastric cancer screening strategies in China using a microsimulation model with different starting and stopping ages and comorbidity profiles, for a total of 378 strategies. 1,000,000 individuals were simulated in the model and followed the alternative strategies. Primary outcomes included gastric cancer incidence, the number of endoscopy and complications, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Future costs and QALYs are discounted by 5% per year. Sensitivity analyses were used to evaluate model uncertainty. Strategies with longer screening durations were associated with higher benefits of life-year gained and gastric cancer deaths averted, but were also accompanied by a large number of endoscopy screening, and complication events. Using the threshold of US$18,575 per QALY gained, at the no, moderate, and severe comorbidity level, the leading cost-effectiveness strategies were the new gastric cancer screening scoring system strategy (NGCS) screening from age 40 years to 60 years (40-60), 40-55-NGCS, and 40-55-NGCS strategy, respectively. The results are robust in sensitivity analyses. Our study illustrates the importance of considering comorbidity conditions and age when determining the starting and stopping screening age for gastric cancer and informs the discussion on personalizing decisions. The trade-off between benefits and harms can also be referenced when necessary.

Catastrophic health expenditure and health-related quality of life among older adults in Shandong, China: the moderation effect of daily care by adult children.

BACKGROUND: Catastrophic health expenditure (CHE) has a considerable impact on older people in later life, but little is known about the relationship between catastrophic health expenditure and health-related quality of life (HRQOL). The aim of this study was to examine the relationship between catastrophic health expenditure and health-related quality of life in older people, and to explore whether the daily care provided by adult children is a moderator in this relationship. METHODS: Data from the sixth National Health Services Survey in Shandong Province, China. The sample consisted of 8599 elderly people (age ≥ 60 years; 51.7% of female). Health-related quality of life was measured by the health utility value of EQ-5D-3 L. Interaction effects were analyzed using Tobit regression models and marginal effects analysis. RESULTS: The catastrophic health expenditure prevalence was 60.5% among older people in Shandong, China. catastrophic health expenditure was significantly associated with lower health-related quality of life (ß= - 0.142, P < 0.001). We found that adult children providing daily care services to their parents mitigated the effect of catastrophic health expenditure on health-related quality of life among older people (ß = 0.027, P = 0.040). CONCLUSIONS: Our findings suggested that catastrophic health expenditure was associated with health-related quality of life and the caring role of older adult children moderated this relationship. Reducing the damage caused by catastrophic health expenditure helps to improve health-related quality of life in older people. Adult children should increase intergenerational contact, provide timely financial and emotional support to reduce the negative impact of catastrophic health expenditure on health-related quality of life.

The mediating effect of sleep quality on solid cooking fuel use and psychological distress among rural older adults: evidence from Shandong, China.

BACKGROUND: Exposure to indoor air pollution from solid cooking fuel use may increase mental disorders risk through pathways such as oroxidative stress, neuroinflammation, or cerebrovascular damage. However, few studies have explored the underlying mechanism between solid cooking fuel use and psychological distress. The present study aims to investigate the mediating role of sleep quality on the relationship between solid cooking fuel use and psychological distress among older adults in rural Shandong, China. METHODS: This study used the cross-sectional data from the second follow-up survey of the Shandong Rural Elderly Health Cohort (SREHC). A total of 3,240 rural older adults were included in the analysis. Logistic regression and the Karlson, Holm, and Breen (KHB) mediation analyses were performed to investigate the relationship between solid cooking fuel use and psychological distress, as well as the mediating role of sleep quality in this association. RESULTS: This study found that solid cooking fuel use was significantly and positively associated with psychological distress among older adults in rural Shandong, China (OR = 1.38, 95% CI: 1.12,1.70). Mediation analysis revealed that sleep quality mediated the association between solid cooking fuel use and psychological distress among older adults (ß = 0.06, P = 0.011). The mediation effect accounted for 16.18% of the total effect. CONCLUSIONS: Our study showed that solid cooking fuel use was associated with psychological distress among rural older adults, and sleep quality mediated this association. Interventions should focus on addressing cooking fuel types and poor sleep quality to reduce psychological distress. In the future, more aggressive environmental protection policies would be needed to lessen the adverse effects of indoor air pollution on the health of older adults in rural China.

Activities of daily living limitations and the use of physical examination among older adults with informal care in China: do gender and residence make differences?

BACKGROUND: This study investigated the relationship between activities of daily living (ADL) limitations and the use of physical examination among older adults receiving informal care, and to further examine whether this relationship varies by gender and urban-rural areas. METHODS: The data in this study were obtained from the sixth Health Service of Shandong province, China. In total, 8,358 older adults aged 60 years or older who received informal care were included in the analysis. Binary logistic regression models were conducted to explore the association between ADL limitations and the use of physical examination and examine the differences between gender and urban-rural areas. RESULTS: The prevalence of limitations in ADL and physical examination utilization rate among older adults receiving informal care in Shandong Province were 14.12% and 72.31%, respectively. After adjusting for confounders, ADL limitations were negatively correlated with the utilization of physical examination services among older adults receiving informal care (OR = 0.74, 95% CI: 0.64, 0.87, P < 0.001), and there were gender and rural-urban differences. The association between ADL limitations and the use of physical examination was statistically significant in older women receiving informal care (OR = 0.65, 95% CI: 0.53, 0.80, P < 0.001). And only among urban older adults receiving informal care, those with ADL limitations had lower utilization of physical examination services than participants without ADL limitations (OR = 0.59, 95% CI: 0.47, 0.74, P < 0.001). CONCLUSIONS: Our study suggested that the relationship between ADL limitations and the use of physical examination among older adults receiving informal care differed by gender and urban-rural areas in Shandong, China. These findings implied that the government should provide more health resources and personalized physical examination service programs, especially to meet the differential needs of women and urban old adults receiving informal care, to contribute to the implementation of healthy aging strategies.

Interaction Between Hypoxia-Inducible Factor 1-alpha Gene Polymorphism and Helicobacter pylori Infection on Gastric Cancer in a Chinese Tibetan Population.

To investigate the impact of four single nucleotide polymorphisms (SNPs) of the HIF1α gene and its interaction with Helicobacter pylori (H. pylori) infection on susceptibility to gastric cancer (GC).Logistic regression was used to test the relationship between four SNPs of HIF1α gene and the susceptibility of GC. A generalized multifactor dimensionality reduction (GMDR) model was used to assess the HIF1α gene-H. pylori infection interaction.Logistic regression analysis indicated that both the rs11549465-CT genotype and the T allele were associated with an increased risk of GC, adjusted OR (95% CI) were 1.63 (1.09-2.20) (CT vs. CC) and 1.70 (1.13-2.36) (T vs. C), respectively. We also found that both the rs11549467-A allele and rs11549467-GA genotype were associated with an increased risk of GC, and adjusted OR (95% CI) were 2.21 (1.61-2.86) (GA vs. GG), 2.13 (1.65-2.65) (A vs. G), respectively. However, no statistically significant impact of rs2057482 or rs1957757 on risk of GC was found. The GMDR model indicated a statistically significant two-dimensional model combination (including rs11549467 and H. pylori infection). The selected model had testing balanced accuracy of 0.60 and the best cross-validation consistencies of 10/10 (p = 0.0107). Compared with H. pylori infection negative participants with rs11549467-GG genotype, H. pylori positive participants with the rs11549467-GA genotype had the highest GC risk, the OR (95% CI) was 3.04 (1.98-4.12).The rs11549467-A allele and rs11549467-GA genotype was associated with increased GC risk. Additionally, the gene-environment interaction between HIF-1α-rs11549467 and H. pylori infection was also correlated with an increased risk of GC.

Quantitative analysis of adipose tissue for predicting Crohn's disease postoperative endoscopic recurrence and anastomotic ulcer.

OBJECTIVE: Inflammation and ulcers at the anastomotic site are frequently observed after intestinal resection surgery for Crohn's disease (CD), which often signify postoperative recurrence. Crohn's disease causes abnormalities in whole-body fat metabolism, and alterations in subcutaneous and visceral fat are potential indicators of disease development. This study aimed to quantify the areas of subcutaneous (SFA) and visceral fat (VFA) and investigate the relationship between fat tissue and endoscopic recurrence and anastomotic ulceration after Crohn's disease surgery. METHODS: We conducted a retrospective analysis of clinical data from 279 patients diagnosed with Crohn's disease. Using abdominal CT (Computed Tomography) scans at the level of the umbilicus, we measured the area of subcutaneous and visceral fat, and calculated the Mesenteric Fat Index (MFI), which is defined as the ratio of the area of visceral fat to subcutaneous fat. We compared the changes in fat tissue between surgical Crohn's disease patients and non-surgical patients in remission, as well as changes in fat tissue before and after surgery, and between patients with and without endoscopic recurrence after surgery. RESULTS: The MFI value of the surgical group was higher than that of the non-surgical group(0.88(1.27 ± 1.26) VS 0.39(0.44 ± 0.21), P < 0.001), while the SFA value was lower(70.16(92.97 ± 78.23) VS 157.64(175.96 ± 101.58), P < 0.001). Of the 134 surgical patients who underwent abdominal CT examination after surgery, the SFA value was significantly higher after surgery(143.61 ± 81.86 VS 90.87 ± 71.93, P < 0.001), and the MFI value decreased accordingly(0.57 ± 0.36 VS 1.30 ± 1.35, P < 0.001). Multivariate Cox analysis indicated that high VFA and MFI values, smoking history, and preoperative biologic therapy were all risk factors for postoperative endoscopic recurrence(p < 0.05), while high MFI values and preoperative biologic therapy were also risk factors for anastomotic ulcers(p < 0.05). The Kaplan-Meier analysis showed that these factors increased the risk of reaching the endpoint with time(p < 0.05). The ROC curve results showed that MFI value had high diagnostic value for postoperative endoscopic recurrence [AUC:0.831, 95% CI: 0.75-0.91, p < 0.001] and anastomotic ulcers [AUC:0.801, 95% CI: 0.71-0.89, p < 0.001]. CONCLUSIONS: Surgical CD patients have significantly higher MFI values but the values decline after surgery. When the preoperative MFI value is > 0.82, the risk of postoperative endoscopic recurrence increases significantly, and when the MFI value is ≥ 1.10, the risk of anastomotic ulceration after surgery increases significantly. Meanwhile, biologic therapy preoperatively also is a high-risk factor for early postoperative endoscopic recurrence or anastomotic ulcers after intestinal resection surgery.

The Effect of Polymer Blends on the In Vitro Release/Degradation and Pharmacokinetics of Moxidectin-Loaded PLGA Microspheres.

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC0-t = 596.53 ng/mL·d, Cave (day 30-day 60) = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.

Quercetin Reprograms Immunometabolism of Macrophages via the SIRT1/PGC-1α Signaling Pathway to Ameliorate Lipopolysaccharide-Induced Oxidative Damage.

The redox system is closely related to changes in cellular metabolism. Regulating immune cell metabolism and preventing abnormal activation by adding antioxidants may become an effective treatment for oxidative stress and inflammation-related diseases. Quercetin is a naturally sourced flavonoid with anti-inflammatory and antioxidant activities. However, whether quercetin can inhibit LPS-induced oxidative stress in inflammatory macrophages by affecting immunometabolism has been rarely reported. Therefore, the present study combined cell biology and molecular biology methods to investigate the antioxidant effect and mechanism of quercetin in LPS-induced inflammatory macrophages at the RNA and protein levels. Firstly, quercetin was found to attenuate the effect of LPS on macrophage proliferation and reduce LPS-induced cell proliferation and pseudopodia formation by inhibiting cell differentiation, as measured by cell activity and proliferation. Subsequently, through the detection of intracellular reactive oxygen species (ROS) levels, mRNA expression of pro-inflammatory factors and antioxidant enzyme activity, it was found that quercetin can improve the antioxidant enzyme activity of inflammatory macrophages and inhibit their ROS production and overexpression of inflammatory factors. In addition, the results of mitochondrial morphology and mitochondrial function assays showed that quercetin could upregulate the mitochondrial membrane potential, ATP production and ATP synthase content decrease induced by LPS, and reverse the mitochondrial morphology damage to a certain extent. Finally, Western blotting analysis demonstrated that quercetin significantly upregulated the protein expressions of SIRT1 and PGC-1α, that were inhibited by LPS. And the inhibitory effects of quercetin on LPS-induced ROS production in macrophages and the protective effects on mitochondrial morphology and membrane potential were significantly decreased by the addition of SIRT1 inhibitors. These results suggested that quercetin reprograms the mitochondria metabolism of macrophages through the SIRT1/PGC-1α signaling pathway, thereby exerting its effect of alleviating LPS-induced oxidative stress damage.

[Expression of Cyclooxygenase-2 in Patients With Snow-White Sign of Advanced Colorectal Adenomas].

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age (P=0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P>0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas (P=0.004),large adenomas (P=0.006),adenomas in distal colon (P=0.015),protruding polyps (P=0.044),and late-stage pathology (P=0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification (P=0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign (P<0.001,P=0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign (P=0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign (P=0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

MiR-196a promotes the proliferation and migration of esophageal cancer via the UHRF2/TET2 axis.

The aim of this study was to investigate the functions and molecular mechanism of miR-196a in esophageal cancer (EC). miR-196a as well as UHRF2 and TET2 mRNA and protein levels in EC tissues and cells were detected using quantitative real-time PCR or western blot, respectively. Cell proliferation was evaluated via MTT assay. Transwell assays were used to detect cell migration. In addition, the targeted relationship between miR-196a and UHRF2 was assessed through a dual luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the levels of the cytosine intermediates 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). We found increased miR-196a expression in EC tissues and cells but decreased UHRF2 and TET2 expression. Next, functional experiments showed that knockdown of miR-196a or UHRF2 overexpression suppress EC cell proliferation and migration. miR-196a negatively regulates TET2 expression by directly targeting UHRF2. UHRF2 overexpression decreased 5mC levels but increased 5hmC levels. Furthermore, TET2 downregulation reversed the functions of miR-196a inhibition on EC cell proliferation and migration. Collectively, our study suggested that miR-196a was closely related to the progression of EC possibly by regulating the UHRF2/TET2 axis. Thus, miR-196a represents a potential new EC therapeutic target.

Diagnosis and treatment of Helicobacter pylori infection by physicians in China: A nationwide cross-sectional study.

BACKGROUND: To investigate the current state of knowledge and practice of Helicobacter pylori (H. pylori) infection management in China. MATERIALS AND METHODS: This nationwide, multicenter, cross-sectional questionnaire survey was conducted between March and April 2021 with respect to the diagnosis and treatment of H. pylori infection in 31 provinces, encompassing over 1000 hospitals in mainland China. General physician information, diagnostic and detection status, eradication treatment, reexamination and follow-up after treatment, and basic knowledge of physicians were collected and compared with the Fifth Chinese National Consensus Report on Management of H. pylori infection and the 2016 Maastricht V/Florence guidelines. The subgroup analysis was also performed. RESULTS: Of the 6873 questionnaire respondents, 48.8% were males, and 51.2% were females. Approximately, 26.5% of respondents indicated that their hospitals had dedicated clinics for managing H. pylori infection. Moreover, 88.0% of respondents prescribed a bismuth-containing quadruple regimen as the initial eradication treatment, and 92.7% deemed the gastric acid suppression critical. Furthermore, 91.0% of respondents routinely recommended a reexamination 1-2 months after eradication therapy, and 95.1% advised patients to stop PPI treatment at least 2 weeks before reexamination. The detail of following (the choice of target population/methods; the choice/availability of drugs/regimens, indications for eradication, factors influencing eradication efficacy/improvement methods and factors influencing adherence, management options/factors influencing relapse; the timing and methods, awareness of reinfection rates/prevention measures, and the approach to continuing education, awareness of guidelines, and acceptance of current core concepts of management) was also described. Subgroup analysis further revealed that significant differences were existed in being gastroenterologist or not, different education level, professional title, years of working, and provincial administrative regions. CONCLUSIONS: Chinese physicians' skills and knowledge about the diagnosis and treatment of H. pylori infection could be improved. More works on education are needed in future.

Safety and efficacy of surgical and endoscopic resection in the treatment of duodenal subepithelial lesions.

BACKGROUND: Duodenal subepithelial lesions (D-SELs) are rare and their resection is challenging. Unfortunately, data on surgical and endoscopic resection of D-SELs are scarce. This study aimed to assess the safety and efficacy of surgical resection and endoscopic resection (ER) for D-SELs. METHODS: We retrospectively analyzed clinical data of patients with non-ampullary D-SELs who underwent ER or surgery and compared the outcomes between ER and surgery with no/low-risk SELs over 15 mm from March 2010 to August 2020. Clinicopathologic findings, procedure-related parameters, and follow-up data were analyzed. RESULTS: A total of 107 patients (108 lesions) were enrolled; 52 patients (53 lesions) received ER and 55 patients (55 lesions) received surgery. In ER group, en bloc resection rate and R0 resection rate were 94 and 89%, respectively. Major adverse events rate was 6%. One (2%) patient experienced local recurrence. In surgery group, R0 resection was achieved in all cases. Major adverse events rate was 20%. Recurrence rate and distant metastases rate were 4 and 8%, respectively. One (2%) patient died from septicemia during follow-up. Thirty-three patients in each group were enrolled in the comparison. There were no significant differences in age, sex, lesion size and location (P > 0.05). More histologically GISTs and muscularis propria-originated lesions were treated by surgery (P < 0.05). ER was significantly associated with a shorter operation time, shorter hospital stay, lower cost, less estimated blood loss, and lower major adverse events rate compared to the surgery group (P < 0.05). However, R0 resection rate, mortality, recurrence rate, and metastases rate were not significant different (P > 0.05). CONCLUSIONS: ER is an effective and safe treatment modality for selected patients with non-ampullary D-SELs by expert endoscopists. Surgery is a radical method for D-SELs that should be reserved for D-SELs not amenable to ER.

Proteomic analysis of small extracellular vesicles from the plasma of patients with hepatocellular carcinoma.

PURPOSE: Liver cancer is one of the most common tumors with the seventh-highest incidence and the third-highest mortality. Many studies have shown that small extracellular vesicles (sEVs) play an important role in liver cancer. Here, we report comprehensive signatures for sEV proteins from plasma obtained from patients with hepatocellular carcinoma (HCC), which might be valuable for the evaluation and diagnosis of HCC. METHODS: We extracted sEVs from the plasma of controls and patients with HCC. Differentially expressed proteins in the sEVs were analyzed using label-free quantification and bioinformatic analyses. Western blotting (WB) was used to validate the abovementioned sEV proteins. RESULTS: Proteomic analysis was performed for plasma sEVs from 21 patients with HCC and 15 controls. Among the 335 identified proteins in our study, 27 were significantly dysregulated, including 13 upregulated proteins that were involved predominantly in the complement cascade (complement C1Q subcomponent subunit B (C1QB), complement C1Q subcomponent subunit C (C1QC), C4B-binding protein alpha chain (C4BPA), and C4B-binding protein beta chain (C4BPB)) and the coagulation cascade (F13B, fibrinogen alpha chain (FGA), fibrinogen beta chain (FGB), and fibrinogen gamma chain (FGG)). We verified increased levels of the C1QB, C1QC, C4BPA, and C4BPB proteins in the plasma sEVs from patients with HCC in both the discovery cohort and validation cohort. CONCLUSIONS: The complement cascade in sEVs was significantly involved in HCC progression. C1QB, C1QC, C4BPA, and C4BPB were highly abundant in the plasma sEVs from patients with HCC and might represent molecular signatures.

Structural Characteristics, Antioxidant, and Immunostimulatory Activities of an Acidic Polysaccharide from Raspberry Pulp.

The extraction and characterization of new bioactive plant-derived polysaccharides with the potential for use as functional foods and medicine have attracted much attention. In the present study, A novel acidic polysaccharide (RPP-3a) with a weight-average molecular weight (Mw) of 88,997 Da was isolated from the raspberry pulp. RPP-3a was composed of rhamnose, arabinose, galactose, glucose, mannose, and galacturonic acid at a molar ratio of 13.1:28.6:16.8:1.4:6.2:33.9. Structural analysis suggested that the RPP-3a backbone was composed of repeating units of →4)-ß-Galp-(1→3,4)-α-Rhap-(1→[4)-α-GalAp-(1→4)-α-GalAp-(1→]n with branches at the C-4 position of rhamnose. The side chain of RPP-3a, containing two branch levels, was comprised of α-Araf-(1→, →5)-α-Araf-(1→, →3,5)-α-Araf-(1→, →3)-ß-Galp-(1→, →3,6)-ß-Galp-(1→, →4)-ß-Glcp-(1→, and →2,6)-α-Manp-1→ residues. RPP-3a exhibited moderate reducing power and strong hydroxyl and superoxide anion radical scavenging abilities. RPP-3a significantly promoted the viability of RAW264.7 macrophages by increasing the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) at both the expression and transcriptional levels. In summary, the immunostimulatory and antioxidant activities make RPP-3a a viable candidate as a health-beneficial functional dietary supplement.

Isolation, Structural Characterization and Macrophage Activation Activity of an Acidic Polysaccharide from Raspberry Pulp.

The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is widely distributed, cultivated, and consumed worldwide. In the present study, a homogeneous acidic polysaccharide (RPP-2a), with a weight-average molecular weight (Mw) of 55582 Da, was isolated from the pulp of raspberries through DEAE-Sepharose Fast Flow and Sephadex G-200 chromatography. RPP-2a consisted of rhamnose, arabinose, galactose, glucose, xylose, galacturonic acid and glucuronic acid, with a molar ratio of 15.4:9.6:7.6:3.2:9.1:54.3:0.8. The results of Fourier transform infrared spectroscopy (FT-IR), gas chromatography-mass spectrometer (GC-MS), 1D-, and 2D-nuclear magnetic resonance (NMR) analyses suggested that the backbone of RPP-2a was primarily composed of →2)-α-L-Rhap-(1→, →2,4)-α-L-Rhap-(1→, →4)-α-D-GalAp-(1→, and →3,4)-α-D-Glcp-(1→ sugar moieties, with side chains of α-L-Araf-(1→, α-L-Arap-(1→, and ß-D-Galp-(1→3)-ß-D-Galp-(1→ residues linked to the O-4 band of rhamnose and O-3 band of glucose residues. Furthermore, RPP-2a exhibited significant macrophage activation activity by increasing the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and the expression of inducible nitric oxide synthase (iNOS) and cytokines at the transcriptional level in RAW264.7 cells. Overall, the results indicate that RPP-2a can be utilized as a potential natural immune-enhancing agent.

Thalidomide Attenuates Colitis and Is Associated with the Suppression of M1 Macrophage Polarization by Targeting the Transcription Factor IRF5.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The TNF-α inhibitor thalidomide is reported to be effective for inducing remission in pediatric Crohn's disease (CD) and adults with refractory CD. The mechanisms underlying the immunomodulatory and anti-inflammatory properties of thalidomide are unclear. METHODS: Histological assessments were firstly performed in thalidomide treated UC patients. Then the effect of thalidomide in vivo was detected in DSS-induced murine colitis. The mechanism involving IRF5, and M1 macrophage polarization was investigated by using plasmid transfection, western blotting, and real-time PCR. Finally, AOM/DSS model was used to detect the role of thalidomide in colitis associated cancer. RESULTS: We first found that treatment with thalidomide could ameliorate colon inflammation for 8 weeks and promote mucosal healing in human UC. Moreover, treatment with thalidomide protected mice from dextran sodium sulfate (DSS)-induced acute colitis, with treated mice presenting with a higher body weight, lower histological score, and lower DAI. Concomitantly, in comparison with control mice, mice treated with thalidomide showed accelerated recovery following colitis after 10 days of thalidomide treatment. Mechanistically, we observed that thalidomide could increase epithelial cell self-renewal capacity and modulate M1/M2 polarization by decreasing M1 markers CD86 and CCR7 and increasing M2 protein signatures CD206 and Arg-1. Thalidomide controls M1 macrophage polarization by targeting the transcription factor IRF5. Finally, by using the classical AOM/DSS model, we found that thalidomide-treated mice presented with a lower incidence and growth of colitis-associated carcinoma (CAC) than negative control mice. CONCLUSIONS: In summary, thalidomide suppresses M1 polarization in the inflammatory microenvironment, which not only attenuates colonic inflammation to facilitate mucosal healing after DSS-induced injury but also represses the progression of CAC.

Four Variants of SLCO2A1 Identified in Three Chinese Patients with Chronic Enteropathy Associated with the SLCO2A1 Gene.

BACKGROUND: Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is an enteropathy characterized by multiple small intestinal ulcers of nonspecific histology, also known as chronic nonspecific multiple ulcers of the small intestine. The SLCO2A1 gene encodes a prostaglandin transporter (PGT). AIMS: The aim of this study was to investigate the clinical characteristics of ten Chinese patients with intestinal ulcers of unknown origin, screen them for variants of SLCO2A1, and to investigate the expression of PGT in the small intestinal mucosa of patients with CEAS. METHODS: Ten Chinese patients with intestinal ulcers of unknown origin were included in this study. Blood samples were collected for whole-exome sequencing and Sanger sequencing of candidate gene variants. Immunohistochemical staining was used to investigate the expression of PGT. RESULTS: These ten patients were clinically diagnosed with intestinal ulcers of unknown origin based on criteria established according to earlier publications. Three of them were genetically diagnosed as having CEAS and four candidate variants of the SLCO2A1 gene were identified, among which c.941-1G>A, c.178G>A and c.1681C>T were detected in patients with CEAS for the first time. The terminal ileum was involved in all three patients with CEAS in our study, which was different from the results of Japanese patients. The expression of PGT in the vascular endothelial cells of the intestinal mucosa tissues of patients with CEAS was negative or intermediate. CONCLUSION: We summarized the clinical data of ten Chinese patients with intestinal ulcers of unknown origin and identified three novel SLCO2A1 variants from three patients with CEAS. This study improves our understanding of CEAS and broadens the spectrum of SLCO2A1 variants known to cause CEAS.

Factors that predict the technical difficulty during endoscopic full-thickness resection of a gastric submucosal tumor.

BACKGROUND AND AIM: endoscopic full-thickness resection (EFTR) is widely accepted for the treatment of gastric submucosal tumors (SMTs). However, technical difficulties sometimes occur. The aim of the present study was to assess the safety and efficacy of EFTR for gastric SMTs and to explore risk factors for technical difficulty. METHODS: the clinical data of patients who received EFTR for gastric SMTs was retrospectively collected from April 2011 to September 2019. Efficacy was defined as an en bloc resection. Difficult EFTR was defined as a procedure time ≥ 120 minutes and/or the occurrence of major adverse events, such as major bleeding, abdominal pain or peritonitis. Finally, risk factors for technical difficulty of EFTR such as gender, age, tumor location, size, symptomatic, regular, outgrowth, operator experience and pathology were analyzed in a univariate and multivariate analysis. RESULTS: one hundred SMTs were removed by EFTR. The average surgery time was 75.73 ± 45.9 (range: 20-250) minutes and the average tumor size was 16.23 ± 7.73 (range: 6-40) mm. With regard to efficacy, en bloc resection was achieved in 98 cases (98 %). A total of ten patients (9.9 %) had complications, namely two intra-operative bleeding, one delayed bleeding and seven patients had abdominal pain (overt peritonitis). EFTR was ceased in one patient due to massive intra-operative bleeding and conversion to laparoscopic surgery was necessary. One patient required laparoscopic surgery due to delayed bleeding, and other complications were resolved with a conservative treatment. A total of 18 cases (17.8 %) encountered a difficult EFTR: tumor size ≥ 3 cm (p = 0.008) and location at the gastric corpus (p = 0.007) were risk factors for a difficult EFTR according to the logistic analysis. CONCLUSION: EFTR is safe and effective for the treatment of gastric SMTs. Tumor size of ≥ 3 cm and location at the gastric corpus are risk factors for a difficult EFTR.

Gastric per-oral endoscopic myotomy (G-POEM) is a promising treatment for refractory gastroparesis: a systematic review and meta-analysis.

AIM: to evaluate the efficacy and safety of gastric per-oral endoscopic myotomy (G-POEM) for the treatment of refractory gastroparesis. METHODS: PubMed, Embase and Cochrane databases were searched and used for study inclusion. Clinical studies since January 2013 to October 2019 were identified as suitable for inclusion. Conference papers, review articles, case reports, animal studies, letters, studies with repetitive data, studies that did not mention the Gastroparesis Cardinal Symptom Index (GCSI) score/gastric emptying scintigraphy (GES) hours or were not indicated in the standard form were excluded. GCSI score, GCSI reduction, gastric emptying scintigraphy at four hours (GES-4h) and GES time (GET) reduction were considered as major indexes and the meta-analysis was achieved using Review Manager 5.3. Research bias was measured according to Cochrane handbook. RESULTS: nine studies were included with a total of 235 patients that underwent G-POEM, and the technical success rate was 100%. After G-POEM, patients reported changes in GCSI score (6/9 studies, mean difference 1.41 [CI: 0.93, 1.88], p < 0.0001), GCSI reduction (8/9 studies, odds ratio 3.00 [CI: 2.24, 4.03], p < 0.0001), GES-4h (8/9 studies, mean difference 23.78 [CI: 19.88, 27.68], p < 0.00001) and GET reduction (6/9 studies, odds ratio 3.50 [CI: 2.12, 5.78], p < 0.00001). The intra-procedure complication rate was 5.1% (12/235), including capnoperitoneum (seven cases) and accidental mucotomy (five cases). The post-procedure complication rate was 6.8% (16/235), including abdominal pain (three cases), bleeding (three cases), ulcer (one case), difficulty swallowing (one case) and others (eight cases). Both per- and post-procedure complications were easily managed by conservative or endoscopic treatments. CONCLUSION: the results show that gastroparesis patients can benefit from G-POEM, the success rate was impressive and the complication rate was relatively low. However, caution is necessary when interpreting the results, primarily due to the limitations of uncontrolled studies. Randomized control studies are still needed for further evaluations.