Tolypocladium sinense Mycelium Polysaccharide Alleviates Obesity, Lipid Metabolism Disorder, and Inflammation Caused by High Fat Diet via Improving Intestinal Barrier and Modulating Gut Microbiota.

SCOPE: Tolypocladium sinense is a fungus isolated from Cordyceps. Cordyceps has some medicinal value and is also a daily health care product. This study explores the preventive effects of T. sinense mycelium polysaccharide (TSMP) on high-fat diet-induced obesity and chronic inflammation in mice. METHODS AND RESULTS: Here, the study establishes an obese mouse model induced by high-fat diet. In this study, the mice are administered TSMP daily basis to evaluate its effect on alleviating obesity. The results show that TSMP can significantly inhibit obesity and alleviate dyslipidemia by regulating the expression of lipid metabolism-related genes such as liver kinase B1 (LKB1), phosphorylated AMP-activated protein kinase (pAMPK), peroxisome proliferator activated receptor α (PPARα), fatty acid synthase (FAS), and hydroxymethylglutaryl-CoA reductase (HMGCR) in the liver. TSMP can increase the protein expression of zona occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon, improve the intestinal barrier dysfunction, and reduce the level of serum LPS, thereby reducing the inflammatory response. 16S rDNA sequencing shows that TSMP alters the intestinal microbiota by increasing the relative abundance of Akkermansia, Lactobacillus, and Prevotellaceae_NK3B31_group, while decreasing the relative abundance of Faecalibaculum. CONCLUSION: The findings show that TSMP can inhibit obesity and alleviates obesity-related lipid metabolism disorders, inflammatory responses, and oxidative stress by modulating the gut microbiota and improving intestinal barrier.

Hematuria after nocturnal exercise of a man: A case report.

BACKGROUND: A man experienced multiple episodes of macroscopic hematuria following nocturnal exercise. Urinary stones and tumors were considered the two most likely causes. The patient had two hobbies: Consuming health care products in large quantities and engaging in late-night running. CASE SUMMARY: Health care products contain a large amount of calcium phosphate, and we hypothesize that this could induce the formation of small phosphate stones. After exercise, the urinary system is abraded, resulting in bleeding. The patient was advised to stop using the health care products. Consequently, the aforementioned symptoms disappeared immediately. However, the patient resumed the above two habits one year later; correspondingly, the macroscopic hematuria reappeared. CONCLUSION: This finding further confirmed the above inference and allowed for a new avenue to determine the cause of the patient's hematuria.

Optimal peritoneal cancer index cutoff point for predicting surgical resectability of pseudomyxoma peritonei in treatment-naive patients.

BACKGROUND: The peritoneal cancer index (PCI) has been used to predict surgical outcomes for pseudomyxoma peritonei (PMP). The present study aimed to establish the optimal cutoff point for PCI to predict surgical resectability of PMP. METHODS: A total of 366 PMP patients were included. The patients were divided into low-grade and high-grade groups. Based on the completeness of the cytoreduction (CC) score, both low-grade and high-grade PMP patients were further divided into complete cytoreductive surgery (CRS) and maximal tumor debulking (MTD) subgroups. The ability to predict surgical resectability of total and selected PCI (regions 2 + 9 to 12) was analyzed through receiver operating characteristic (ROC) curves. RESULTS: Both total and selected PCI demonstrated excellent discriminative ability in predicting surgical resectability for low-grade PMP patients (n = 266), with the ROC-AUC of 0.940 (95% CI: 0.904-0.965) and 0.927 (95% CI: 0.889-0.955). The corresponding optimal cutoff point was 21 and 5, respectively. For high-grade PMP patients (n = 100), both total and selected PCI exhibited good performance in predicting surgical resectability, with the ROC-AUC of 0.894 (95% CI: 0.816-0.946) and 0.888 (95% CI: 0.810-0.943); correspondingly, the optimal cutoff point was 25 and 8, respectively. The discriminative ability between total and selected PCI in predicting surgical resectability did not show a statistical difference. CONCLUSIONS: Both total and selected PCI exhibited good performance and similarity in predicting complete surgical resection for both low-grade and high-grade PMP patients. However, the selected PCI was simpler and time-saving in clinical practice. In the future, new imaging techniques or predictive models may be developed to better predict PCI preoperatively, which might assist in confirming whether complete surgical resection can be achieved.

Bland-Altman agreement analysis between CT predicted and surgical peritoneal cancer index in pseudomyxoma peritonei of appendiceal origin.

Peritoneal cancer index (PCI) is the surgical variable most commonly used to quantify the extent of peritoneal metastases for pseudomyxoma peritonei (PMP) patients. The present study aimed to investigate the agreement between CT predicted and surgical PCI by the Bland-Altman method for PMP of appendiceal origin. A total of 167 PMP patients of appendiceal origin were included between 2016 and 2021. Bland-Altman analysis was performed for both total PCI and selected PCI (regions 2 + 9-12). After the Bland-Altman plot was drawn, the mean bias and its 95% limit of agreements (LoAs) was quantified. Besides, the correlation coefficients between CT-PCI and surgical PCI were also been calculated. The Bland-Altman plot showed the mean bias ± SD between total CT-PCI and surgical PCI as 0.431 ± 3.005, with the LoAs from - 5.459 to 6.321. There were nine points of difference in total PCI exceeded the 95% LoAs, with the rate of 5.39% (9/167). As for selected CT-PCI, Bland-Altman plot showed the mean bias ± SD between selected CT-PCI and surgical PCI as - 0.287 ± 1.955, with the LoAs from - 4.118 to 3.544. There were ten points of difference in selected PCI exceeded the 95% LoAs, with the rate of 5.99% (10/167). The Spearman's rank correlation coefficient between total CT-PCI and surgical PCI was 0.911, P < 0.001, as for selected CT-PCI and surgical PCI, the coefficient was 0.909, P < 0.001. Although there was a strong correlation for both total and selected CT-PCI with surgical PCI, however, the agreement is still not good in Bland-Altman analysis, which suggested that CT-PCI cannot predict surgical PCI accurately even in professional PMP treatment centers. In brief explanation, CT makes it difficult to distinguish the borderline between tumor tissue and mucus and to detect tumor lesions in the small intestine regions, which caused overestimation or underestimation by CT-PCI. In the future, a multiple linear regression model based on CT-PCI might accurately predict surgical PCI preoperatively.

Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice.

Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.

Preoperative plasma D-Dimer level is correlated with peritoneal cancer index of patients with pseudomyxoma peritonei.

PURPOSE: Accurate assessment of preoperative tumor burden contribute to formulate a scientific surgical plan for patients with pseudomyxoma peritonei (PMP). Present study aimed to assess whether the preoperative plasma D-Dimer level could reflect tumor burden for PMP patients. METHODS: A total of 253 PMP patients were included between June 1, 2013 and March 1, 2022. According to the peritoneal cancer index (PCI), all participants were divided into extensive (PCI ≥ 28) and none-extensive (PCI < 28) subgroups. The D-Dimer and tumor markers were compared between the two subgroups. The correlation between the abovementioned biomarkers and PCI will be calculated, and further compared with each other. Two-sided P value less than 0.05 is considered statistically significant. RESULTS: The level of D-Dimer (ng/ml) between extensive and none-extensive subgroup were 600 (328, 1268) vs. 339 (128, 598), Z = -5.425, p < 0.001. The Spearman correlation between D-Dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), CA 19 - 9 and PCI were 0.487, 0.509, 0.469, and 0.499, respectively (all p < 0.001). The correlation coefficients were compared with each other according to Meng, Rosenthal and Rubin's method, however, there was no significant difference. CONCLUSION: Preoperative plasma D-Dimer could moderately reflect tumor burden for PMP. In the future, a multivariate prediction model will be developed to help surgeons to formulate a more precise surgical plan for the PMP patients.

Nomogram to Predict Incomplete Cytoreduction for Pseudomyxoma Peritonei.

BACKGROUNDS: The completeness of cytoreduction is one of the most important prognostic factors for patients with pseudomyxoma peritonei (PMP). To date, no nomograms have been established to predict incomplete cytoreduction (IC) for patients with PMP. The current study therefore proposed a nomogram to predict individual IC risk for PMP patients. METHODS: Between 1 June 2013, and 22 November 2019, 144 consecutive PMP patients who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the first time in our center were included in a retrospective study. Possible predictors of cytoreducibility were analyzed using logistic regression modeling to predict IC for PMP patients. A nomogram was developed based on the multivariate analysis and further investigated for internal validation. RESULTS: After CRS, the 144 participants were divided into complete CRS (CCRS) (n = 46) and IC (n = 98) subgroups. Four independent predictors (sex, disease duration, anemia, and carbohydrate antigen 19-9 (CA 199)) were included in the prediction model. Then, a nomogram predicting IC was established based on the aforementioned variables, which demonstrated good predictive accuracy (C-index, 0.837; 95 % confidence interval [CI], 0.764-0.894). The predicted probability was close to the actual observed outcome according to the calibration plot. CONCLUSIONS: The current work led to the development of a nomogram capable of predicting IC for PMP patients who demonstrated good performance. Risk stratification by the established nomogram had ability to optimize individual IC prediction and help physicians to establish meticulous preoperative plans.

Alterations and correlations of gut microbiota, fecal, and serum metabolome characteristics in a rat model of alcohol use disorder.

Background: Growing evidence suggests the gut microbiota and metabolites in serum or fecal may play a key role in the process of alcohol use disorder (AUD). However, the correlations of gut microbiota and metabolites in both feces and serum in AUD subjects are not well understood. Methods: We established a rat model of AUD by a chronic intermittent ethanol voluntary drinking procedure, then the AUD syndromes, the gut microbiota, metabolomic profiling in feces and serum of the rats were examined, and correlations between gut microbiota and metabolites were analyzed. Results: Ethanol intake preference increased and maintained at a high level in experimental rats. Anxiety-like behaviors was observed by open field test and elevated plus maze test after ethanol withdraw, indicating that the AUD rat model was successfully developed. The full length 16S rRNA gene sequencing showed AUD significantly changed the ß-diversity of gut microbial communities, and significantly decreased the microbial diversity but did not distinctly impact the microbial richness. Microbiota composition significantly changed in AUD rats, such as the abundance of Romboutsia and Turicibacter were significantly increased, whereas uncultured_bacterium_o_Mollicutes_RF39 was decreased. In addition, the untargeted metabolome analysis revealed that many metabolites in both feces and serum were altered in the AUD rats, especially involved in sphingolipid metabolism and glycerophospholipid metabolism pathways. Finally, multiple correlations among AUD behavior, gut microbiota and co-changed metabolites were identified, and the metabolites were directly correlated with the gut microbiota and alcohol preference. Conclusion: The altered metabolites in feces and serum are important links between the gut microbiota dysbiosis and alcohol preference in AUD rats, and the altered gut microbiota and metabolites can be potentially new targets for treating AUD.

Nomogram to predict overall survival of patients with pseudomyxoma peritonei of appendiceal origin: A retrospective cohort study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease, with the rate of overall survival (OS) influenced by many factors. The present study aimed to define independent predictors and establish a nomogram for individual risk prediction in PMP patients. METHODS: One hundred forty-seven PMP patients were consecutively included between June 1, 2013, and November 22, 2019. The log-rank test was used to compare the OS rate between groups; subsequently, variables with p < .10 were subjected to multivariate Cox modeling for defining independent prediction indicators. Finally, a nomogram was established based on independent prognosticators and assessed for internal validation. RESULTS: Multivariate Cox analysis showed that D-dimer level, carbohydrate antigen (CA) 125 level, CA 19-9 level, degree of radical surgery, and histological grade were all independently associated with OS in PMP patients. A nomogram was plotted and underwent internal validation. The discrimination ability of the nomogram revealed a good predictive ability as indicated by the C-index value (0.825), and calibration plots confirmed good consistency between the predicted and observed survival probabilities. CONCLUSIONS: Five independent prognostic factors for predicting the survival of PMP patients were identified, and the nomogram based on these independent indicators showed a reasonable discrimination ability for individual risk prediction.

Comparison of detection rate of 16 sampling methods for respiratory viruses: a Bayesian network meta-analysis of clinical data and systematic review.

BACKGROUND: Respiratory viruses (RVs) is a common cause of illness in people of all ages, at present, different types of sampling methods are available for respiratory viral diagnosis. However, the diversity of available sampling methods and the limited direct comparisons in randomised controlled trials (RCTs) make decision-making difficult. We did a network meta-analysis, which accounted for both direct and indirect comparisons, to determine the detection rate of different sampling methods for RVs. METHODS: Relevant articles were retrieved comprehensively by searching the online databases of PubMed, Embase and Cochrane published before 25 March 2020. With the help of R V.3.6.3 software and 'GeMTC V.0.8.2' package, network meta-analysis was performed within a Bayesian framework. Node-splitting method and I2 test combined leverage graphs and Gelman-Rubin-Brooks plots were conducted to evaluate the model's accuracy. The rank probabilities in direct and cumulative rank plots were also incorporated to rank the corresponding sampling methods for overall and specific virus. RESULTS: 16 sampling methods with 54 438 samples from 57 literatures were ultimately involved in this study. The model indicated good consistency and convergence but high heterogeneity, hence, random-effect analysis was applied. The top three sampling methods for RVs were nasopharyngeal wash (NPW), mid-turbinate swab (MTS) and nasopharyngeal swab (NPS). Despite certain differences, the results of virus-specific subanalysis were basically consistent with RVs: MTS, NPW and NPS for influenza; MTS, NPS and NPW for influenza-a and b; saliva, NPW and NPS for rhinovirus and parainfluenza; NPW, MTS and nasopharyngeal aspirate for respiratory syncytial virus; saliva, NPW and MTS for adenovirus and sputum; MTS and NPS for coronavirus. CONCLUSION: This network meta-analysis provides supporting evidences that NPW, MTS and NPS have higher diagnostic value regarding RVs infection, moreover, particular preferred methods should be considered in terms of specific virus pandemic. Of course, subsequent RCTs with larger samples are required to validate our findings.

The Old Supracondylar Fracture of Femur Treated by Gradual Deformity Correction Using the Ilizarov Technique Followed by the Second-Stage Internal Fixation in an Elderly Patient With Osteoporosis.

BACKGROUND: The supracondylar nonunion of femur in elderly individuals is rare and challenging to manage. Nothing in English literatures or guidelines is available regarding this particular fracture characterized by osteoporosis, soft-tissue contracture, shortening, and joint stiffness. We report a case of an elderly patient with a supracondylar nonunion of the femur, which was successfully treated using staged Ilizarov techniques and dual plating. CASE PRESENTATION: An 84-year-old female patient was admitted to our orthopedic department for her pain and soft-tissue swelling around the right knee with claudication and shortening deformity of the affected extremity. She denied any specific history of trauma and had sought traditional Chinese medical attention for 6 months before she presented to our hospital. Diagnosis of the right femoral supracondylar nonunion was made based on the X-ray and computed tomography. Ilizarov external fixator was carried out for successive and slow distraction and gradual correction of the shortening deformity, in consideration of the nonunion was still present. Subsequently, internal fixation with dual plating of the distal femur was performed. Excellent function and patient satisfaction were observed at 6 months of follow-up. CONCLUSION: The protocol of Ilizarov technique with subsequent internal fixation of dual plating seems to be an efficient solution to the supracondylar nonunion of femur in elderly patients with osteoporosis. The advantage of the protocol is that it allows knee joint motion, avoids neurovascular complications, and gentle correction of soft-tissue contractures.

Transient EDTA-Dependent Pseudothrombocytopenia Phenomenon in a Patient with Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with arterial/venous thrombosis and pregnancy loss; thrombocytopenia is another common manifestation of APS. In the present study, we discovered a transient ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) phenomenon in APS, which has not yet been reported in the literature.

Urinary Myeloperoxidase to Creatinine Ratio as a New Marker for Diagnosis of Urinary Tract Infection.

Objective To determine whether urinary myeloperoxidase to creatinine ratio (MCR) can serve as a marker for diagnosis of urinary tract infection (UTI).Methods Patients suspected of UTI were consecutively enrolled and further divided into the culture positive and the sterile groups according to urine culture results. Subsequently, MCR, white blood cell (WBC) and bacteria in the urinary samples from patients were detected and compared between the two groups.Results Finally, 253 patients were enrolled including 157 urine culture positive patients and 96 urine culture negative patients (sterile group). After logarithmic transformation in 2 as the base, the MCR, WBC, and bacteria were separately presented as log2 MCR, log2 WBC(quantitative) , and log2 bacteria. The values of log2 MCR(8.6±2.5 vs. 5.4±1.5, t=-12.453, P=0.001), log2 WBC(quantitative) (8.0±2.5 vs. 5.2±1.8, t=-10.332, P=0.001), log2 bacteria (11.4±2.5 vs. 8.2±2.8, t=-9.297, P=0.001) and WBC (semi-quantitative) [2 (interquartile range 1, 3) vs. 1 (interquartile range 0.5, 1), Z=-7.580, P=0.001] showed significant difference between the urine culture positive group and the sterile group. Among the urine culture positive group, the values of log2 MCR of the gram positive and gram negative subgroups were 7.2±2.5 and 9.0±2.4 (t=4.016, P=0.001), respectively. The correlation between log2 MCR and log2 WBC (quantitative), log2 bacteria, WBC (semi-quantitative) was 0.708 (Pearson correlation, P=0.001), 0.381 (Pearson correlation, P=0.001), and 0.606 (Spearman correlation, P=0.001), respectively. Conclusions MCR is positively correlated with WBC counts and could be served as a promising biomarker for diagnosis of UTI. MCR could be even used for initial inference of infectious bacteria types of UTI.

Urinary myeloperoxidase to creatinine ratio as a new marker for monitoring treatment effects of urinary tract infection.

OBJECTIVE: We want to determine whether urinary myeloperoxidase to creatinine ratio could be served as a new marker for monitoring treatment effects of urinary tract infection or not. METHODS: A total of 328 patients suspected of UTI were enrolled in present study. Patients been received antibiotic therapy within two weeks were excluded (n = 26). Patients with urine contaminated specimens (n = 49) and negative urine culture results (n = 96) were also excluded, the remaining culture positive subjects (n = 157) were followed up for 7 to 14 days, finally, a total of 49 subjects were followed up and further divided into cure (n = 35) and none-cure (n = 14) subgroups according to urine culture results. MPO concentration was determined by immunoturbidimetric method and creatinine level was measured by creatinine enzyme method. Two sided P values < 0.05 were considered statistically significant. RESULTS: Urinary MCR level between before and after antibiotic treatment of cure group were (1437.1 ±â€¯1777.9 vs.48.3 ±â€¯59.3, t = 4.608, P = 0.001), respectively. Urinary MCR level between before and after antibiotic treatment of none-cure group were (1633.1 ±â€¯2168.7 vs. 999.4 ±â€¯1708.0, t = 1.809, P = 0.094), respectively. CONCLUSIONS: Urinary MCR could be served as a promising marker for monitoring treatment effects of urinary tract infection.

Neutrophil and Eosinophil Granule Proteins as Potential Biomarkers of Assessing Disease Activity and Severity in Patients With Ulcerative Colitis.

BACKGROUND: Colonoscopy can assess disease activity and severity of ulcerative colitis (UC) accurately, but it is invasive and costly. Role of noninvasive biomarkers of intestinal inflammation in evaluation of patients with UC is not well understood. In this study, we assessed fecal eosinophil cationic protein (FECP), fecal myeloperoxidase (FMPO), and fecal calprotectin (FC) as surrogate markers of disease activity and severity in patients with UC, and then evaluated effect of the combination of these markers. METHODS: Sixty-three UC patients and 59 cases of age-matched controls were investigated. All patients underwent clinical, endoscopic, and histological assessment for disease activity and severity. Fecal samples were analyzed for FECP, FC, and FMPO. RESULTS: All three fecal biomarkers were elevated in patients compared with controls (P = 0.000). Significant differences were found between inactive UC and controls (P = 0.000). Cases with severe UC had significantly higher FECP levels than those with mild UC (p < 0.05), but there were no significant differences in FC and FMPO levels among disease severity groups. All three biomarkers showed positive correlation with Ulcerative Colitis Activity Index (UCAI). The areas under the ROC curve of FECP, FC, and FMPO were 0.939, 0.783, and 0.785, respectively. Sensitivity and specificity of fecal biomarkers in assessing disease activity were FECP-88.46%, 89.47%; FC-80.77%, 68.42%; and FMPO-84.62%, 63.16%. CONCLUSIONS: All three fecal biomarkers could be used as surrogate markers for assessing disease activity of UC, and FECP provided superior discrimination than FMPO and FC. Moreover, FECP could distinguish between mild disease and severe disease group.

Mean Platelet Volume Could Reflect Disease Activity of Adult Patients With Systemic Lupus Erythematosus.

BACKGROUND: In recent years, research regarding mean platelet volume (MPV) has been expanded to numerous diseases. The aim of the present study was to assess whether MPV could reflect disease activity of adult patients with systemic lupus erythematosus (SLE). METHODS: A total of 128 adult patients with SLE were enrolled in the present study and allocated into two subgroups (99 with active phase and 29 with inactive phase) according to SLE disease activity index (SLEDAI). Demographic data, MPV, complement 3 (C3), and complement 4 (C4) were recorded. Independent sample t-test was used for comparison of quantitative variables between the active and inactive groups. Pearson's correlation test was used to evaluate the correlation between the above laboratory indices and the SLEDAI score. RESULTS: The mean MPV level in active patients was significantly higher than inactive subjects (8.3 ± 1.3 vs. 7.7 ± 0.7, p < 0.001). The correlation between MPV level and SLEDAI score was moderate (r = 0.520, p < 0.001). CONCLUSIONS: MPV might be a promising marker to reflect disease activity of adult patients with SLE.