Lipid alterations play a role in the integration of PD-1/PD-L1 inhibitors and anlotinib for the treatment of advanced non-small-cell lung cancer.

BACKGROUND: Studies have shown that integrating anlotinib with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors enhances survival rates among progressive non-small-cell lung cancer (NSCLC) patients lacking driver mutations. However, not all individuals experience clinical benefits from this therapy. As a result, it is critical to investigate the factors that contribute to the inconsistent response of patients. Recent investigations have emphasized the importance of lipid metabolic reprogramming in the development and progression of NSCLC. METHODS: The objective of this investigation was to examine the correlation between lipid variations and observed treatment outcomes in advanced NSCLC patients who were administered PD-1/PD-L1 inhibitors alongside anlotinib. A cohort composed of 30 individuals diagnosed with advanced NSCLC without any driver mutations was divided into three distinct groups based on the clinical response to the combination treatment, namely, a group exhibiting partial responses, a group manifesting progressive disease, and a group demonstrating stable disease. The lipid composition of patients in these groups was assessed both before and after treatment. RESULTS: Significant differences in lipid composition among the three groups were observed. Further analysis revealed 19 differential lipids, including 2 phosphatidylglycerols and 17 phosphoinositides. CONCLUSION: This preliminary study aimed to explore the specific impact of anlotinib in combination with PD-1/PD-L1 inhibitors on lipid metabolism in patients with advanced NSCLC. By investigating the effects of using both anlotinib and PD-1/PD-L1 inhibitors, this study enhances our understanding of lipid metabolism in lung cancer treatment. The findings from this research provide valuable insights into potential therapeutic approaches and the identification of new therapeutic biomarkers.

A combined radiomic model distinguishing GISTs from leiomyomas and schwannomas in the stomach based on endoscopic ultrasonography images.

BACKGROUND: Endoscopic ultrasonography (EUS) is recommended as the best tool for evaluating gastric subepithelial lesions (SELs); nonetheless, it has difficulty distinguishing gastrointestinal stromal tumors (GISTs) from leiomyomas and schwannomas. GISTs have malignant potential, whereas leiomyomas and schwannomas are considered benign. PURPOSE: This study aimed to establish a combined radiomic model based on EUS images for distinguishing GISTs from leiomyomas and schwannomas in the stomach. METHODS: EUS images of pathologically confirmed GISTs, leiomyomas, and schwannomas were collected from five centers. Gastric SELs were divided into training and testing datasets based on random split-sample method (7:3). Radiomic features were extracted from the tumor and muscularis propria regions. Principal component analysis, least absolute shrinkage, and selection operator were used for feature selection. Support vector machine was used to construct radiomic models. Two radiomic models were built: the conventional radiomic model included tumor features alone, whereas the combined radiomic model incorporated features from the tumor and muscularis propria regions. RESULTS: A total of 3933 EUS images from 485 cases were included. For the differential diagnosis of GISTs from leiomyomas and schwannomas, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve were 74.5%, 72.2%, 78.7%, and 0.754, respectively, for the EUS experts; 76.8%, 74.4%, 81.0%, and 0.830, respectively, for the conventional radiomic model; and 90.9%, 91.0%, 90.6%, and 0.953, respectively, for the combined radiomic model. For gastric SELs <20 mm, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the combined radiomic model were 91.4%, 91.6%, 91.1%, and 0.960, respectively. CONCLUSIONS: We developed and validated a combined radiomic model to distinguish gastric GISTs from leiomyomas and schwannomas. The combined radiomic model showed better diagnostic performance than the conventional radiomic model and could assist EUS experts in non-invasively diagnosing gastric SELs, particularly gastric SELs <20 mm.

Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Gut microbiota alterations in chronic pancreatitis (CP) are seldomly described systematically. It is unknown whether pancreatic exocrine insufficiency (PEI) and different etiologies in patients with CP are associated with gut microbiota dysbiosis. METHODS: The fecal microbiota of 69 healthy controls (HCs) and 71 patients with CP were compared to investigate gut microbiome alterations in CP and the relationship among gut microbiome dysbiosis, PEI and different etiologies. Fecal microbiomes were analyzed through 16S ribosomal RNA gene profiling, based on next-generation sequencing. Pancreatic exocrine function was evaluated by determining fecal elastase 1 activity. RESULTS: Patients with CP showed gut microbiota dysbiosis with decreased diversity and richness, and taxa-composition changes. On the phylum level, the gut microbiome of the CP group showed lower Firmicutes and Actinobacteria abundances than the HC group and higher Proteobacteria abundances. The abundances of Escherichia-Shigella and other genera were high in gut microbiomes in the CP group, whereas that of Faecalibacterium was low. Kyoto Encyclopedia of Genes and Genomes pathways (lipopolysaccharide biosynthesis and bacterial invasion of epithelial cells) were predicted to be enriched in the CP group. Among the top 5 phyla and 8 genera (in terms of abundance), only Fusobacteria and Eubacterium rectale group showed significant differences between CP patients, with or without PEI. Correlation analysis showed that Bifidobacterium and Lachnoclostridium correlated positively with fecal elastase 1 (r = 0.2616 and 0.2486, respectively, P < 0.05). CONCLUSIONS: The current findings indicate that patients with CP have gut microbiota dysbiosis that is partly affected by pancreatic exocrine function.

Comparison of smear cytology and liquid-based cytology in EUS-guided FNA of pancreatic lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via EUS-guided FNA (EUS-FNA) are still insufficient, mainly because results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China. METHODS: A retrospective database search (January 2015 to January 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytologic, and endosonographic data were collected from 819 patients; 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were compared. Rapid on-site evaluation was not available in all cases. RESULTS: Three hundred eighty-five cases (74.90%) had confirmed malignancy, and 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and negative predictive value (NPV) of LBC were higher than those of SC with statistical significance (71.4% vs 55.1%, 76.1% vs 61.6%, and 40.6% vs 27.7%, respectively). The sensitivity, accuracy, and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% vs 71.4%, 86.5% vs 76.1%, and 56.8% vs 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions (P = .003), solid lesions (P < .001), 22-gauge needle size (P < .001), and number of needle passage >3 (P = .041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage >3 (P = .017) was associated with higher diagnostic sensitivity using SC. CONCLUSIONS: LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesions with higher NPV when rapid on-site evaluation is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle, and more than 3 passes were associated with higher sensitivity when using LBC. Performing more than 3 passes is associated with higher sensitivity when using SC.

A novel gene arrangement among the Stylommatophora by the complete mitochondrial genome of the terrestrial slug Meghimatium bilineatum (Gastropoda, Arionoidea).

Stylommatophora is a main clade of Gastropoda that encompasses approximately 112 gastropod families and may exceed a total of 30,000 species. Twenty-four complete stylommatophoran mitogenomes have been sequenced to date, yet our understanding of mitochondrial evolution in stylommatophorans is still in its infancy. To further expand the set of available mitogenomes, we sequenced the mitogenome of Meghimatium bilineatum (Arionoidea: Philomycidae), a widespread land slug in East Asia. This is the first report on a mitogenome of the superfamily Arionoidea, and indeed on a terrestrial slug. The mitogenome of Meghimatium bilineatum comprises 13,972 bp and exhibits a novel, highly distinctive gene arrangement among the Stylommatophora. Phylogenetic reconstructions based on the sequences of all protein-coding genes consistently recovered Meghimatium bilineatum as sister-group of the Succineidae. A phylogenetic reconstruction based on gene order, however, suggested a highly divergent tree topology, which is less credible when taking into account prior knowledge of stylommatophoran relationships. Our CREx (Common interval Rearrangement Explorer) analysis suggested that three successive events of tandem duplication random loss (TDRL) best explain the evolutionary process of gene order rearrangement in Meghimatium bilineatum from an ancestral stylommatophoran mitogenome. The present example offers new insights into the mechanisms of mitogenome rearrangements in gastropods at large and into the usefulness of mitogenomic gene order as a phylogenetic marker.

Towards a global phylogeny of freshwater mussels (Bivalvia: Unionida): Species delimitation of Chinese taxa, mitochondrial phylogenomics, and diversification patterns.

The Yangtze River Basin in China is one of the global hotspots of freshwater mussel (order Unionida) diversity with 68 nominal species. Few studies have tested the validity of these nominal species. Some taxa from the Yangtze unionid fauna have not been adequately examined using molecular data and well-positioned phylogenetically with respect to the global Unionida. We evaluated species boundaries of Chinese freshwater mussels, and disentangled their phylogenetic relationships within the context of the global freshwater mussels based on the multi-locus data and complete mitochondrial genomes. Moreover, we produced the time-calibrated phylogeny of Unionida and explored patterns of diversification. COI barcode data suggested the existence of 41 phylogenetic distinct species from our sampled 40 nominal taxa inhabiting the middle and lower reaches of the Yangtze River. Maximum likelihood and Bayesian inference analyses on three loci (COI, 16S, and 28S) and complete mitochondrial genomes showed that the subfamily Unioninae sensu stricto was paraphyletic, and the subfamily Anodontinae should be subsumed under Unioninae. In addition, we described two new tribes (Aculamprotulini tribe nov. and Lepidodesmini tribe nov.) in the subfamily Unioninae and one new genus (Parvasolenaiagen. nov.) in the subfamily Gonideinae. Molecular dating analysis suggested freshwater mussels diversified at 346.1 Mya (HPD = 286.6-409.9). The global diversification rate for Unionida was estimated to be 0.025 species/Myr. Our study found only a single well-supported rate shift in Unionida diversification, occurring at the base of the subfamily Ambleminae. The evolution of active host-attraction may have triggered the burst of speciation in Ambleminae, and the environment and geography of the Mississippi River Basin likely sustained this radiation.

Identification of flavonoids in Dendrobium huoshanense and comparison with those in allied species of Dendrobium by TLC, HPLC and HPLC coupled with electrospray ionization multi-stage tandem MS analyses.

Dendrobium huoshanense, a unique species in the genus Orchidaceae, is only found in China and is known as "mihu". Due to the lack of quality control, the use of D. huoshanense in the herbal market has been limited. In this study, methods based on thin-layer chromatography, high-performance liquid chromatography and high-performance liquid chromatography coupled with electrospray ionization multi-stage tandem mass spectrometry were used to identify the flavonoids in D. huoshanense and distinguish this species from other Dendrobium species. Using thin-layer chromatography, a characteristic band was observed for D. huoshanense, and this band was absent from the thin-layer chromatography plates of other Dendrobium species. Then, using high-performance liquid chromatography, nine peaks of flavonoids were observed in the chromatograms of ten batches of D. huoshanense. Ultimately, 22 flavonoids in D. huoshanense were identified by multi-stage tandem mass spectrometry, and 11 of these compounds are being reported from D. huoshanense for the first time. In addition, two compounds both with molecular weights of 710, were identified as being unique to D. huoshanense; one of these compounds, apigenin-6-C-α-L-rhamnosyl-(1→2)-ß-D-glucoside-8-C-α-L-arabinoside, was proven to be responsible for the characteristic thin-layer chromatography band of D. huoshanense. These analysis methods can be applied for the identification and quality control of D. Huoshanense.

Is ERCP-BD or EUS-BD the preferred decompression modality for malignant distal biliary obstruction? A meta-analysis of randomized controlled trials.

BACKGROUND: endoscopic retrograde cholangiopancreatography (ERCP)-guided biliary drainage (ERCP-BD) with transpapillary stent placement is the standard palliative treatment for malignant distal biliary obstruction. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been evaluated for efficacy and safety as an alternative for failed ERCP. PURPOSE: we aimed to determine whether ERCP-BD or EUS-BD is the preferred treatment modality for decompressing malignant distal biliary obstruction. METHODS: we systematically searched for relevant published, prospective, and randomized trials comparing ERCP-BD with EUS-BD in decompressing malignant distal biliary obstruction in databases (i.e., PubMed and Cochrane). Technical success, treatment success, and procedure duration were primary outcome measurements; overall adverse events, post-ERCP pancreatitis (PEP), and stent reintervention rate were the secondary outcomes. RESULTS: three trials with 220 patients met the inclusion criteria. Technical success, treatment success, procedure duration, and overall adverse event rate were similar between ERCP-BD and EUS-BD. However, ERCP-BD had a significantly higher PEP rate than EUS-BD (9.2% vs. 0%), the difference being significant (risk ratio [RR] = 8.5; 95% confidence interval (CI): 1.03-69.91, p = 0.05). Similarly, ERCP-BD had a higher stent reintervention rate than EUS-BD (28.4% vs. 4.5%), although the difference was not significant (RR = 1.91; 95% CI: 0.94-3.88, p = 0.07). CONCLUSION: technical success, treatment success, procedure duration, and overall adverse event rate were comparable between ERCP-BD and EUS-BD in decompressing malignant distal biliary obstruction. Nevertheless, EUS-BD had a significantly lower rate of PEP and a lower tendency toward stent reintervention than ERCP-BD. Therefore, EUS-BD might be a suitable alternative to ERCP-BD when performed by experts.

Reclassification of Lamprotula rochechouartii as Margaritifera rochechouartiicomb. nov. (Bivalvia: Margaritiferidae) revealed by time-calibrated multi-locus phylogenetic analyses and mitochondrial phylogenomics of Unionoida.

The family Margaritiferidae encompasses 12 valid species, which are distributed widely but disjunctively in the Northern Hemisphere. A lack of a well resolved and temporally calibrated phylogenetic framework of Margaritiferidae has made it difficult to discuss the evolutionary pattern and process. Phylogenetic relationships between five major clades, which were revealed in earlier studies, remain elusive and unresolved. Lamprotula rochechouartii has long been classified within the family Unionidae based on shell morphology, but our preliminary molecular study on this species made us hypothesize that it has an affinity with margaritiferids. Hence, five loci (COI, 16S, 18S, 28S and histone H3) were used to investigate the phylogenetic position of L. rochechouartii and intra-familial relationships within Margaritiferidae using various partitioning strategies. Moreover, two mitochondrial genomes were newly obtained to further resolve and validate the five-clade relationships within Margaritiferidae in a broad view of Unionoida evolution. Both five-gene and mitogenome datasets strongly advocated treating Lamprotula rochechouartii as Margaritifera rochechouartiicomb. nov. Maximum likelihood and Bayesian inference analyses using partitioned five-gene dataset resulted in various topologies, but five well-supported clades were obtained. The most probable cladistic relationships generated by five-gene dataset analyses were identical to subsequent whole mitogenome analyses except the position of M. monodonta. M. rochechouartii and M. laosensis had a well-supported sister relationship and formed a basal clade splitting from the rest of the family. Based on six reliable fossils, crown age of the extant Margaritiferidae was estimated during the Late Cretaceous at 88.3 Ma (95% HPD = 66.2-117.4). But we hypothesized a much earlier origin of this family due to the Permian stem age (mean = 257 Ma, 95% HPD = 230.0-296.0) and a high extinction rate in the whole order. Biogeographic scenarios supported a Laurasian origin of extant Margaritiferidae during the Late Cretaceous, and suggested that Asian margaritiferids may have had two origins, having either Asia (M. rochechouartii, M. laosensis) or North America (M. dahurica, M. laevis, and M. middendorffi) as ancestral. The newly added Margaritiferidae species M. rochechouartii expands our recognized distribution range of modern margaritiferids. Our results indicate that whole mitogenome sequences can be used to reconstruct robust phylogenetic relationships for freshwater mussels, especially with the help of adding M-type mitogenomes.

A Biomimetic Supramolecular Approach for Charge Transfer between Donor and Acceptor Chromophores with Aggregation-Induced Emission.

Supramolecular assembly of chromophores with inherent resistance to aggregation-induced self-quenching is significant to applications such as chemical sensing and organic light emitting diodes (OLEDs). In this work, molecular gels with aggregation-induced emission (AIE) are constructed by simply coassembling AIE chromophores (electron donor or acceptor) with a nonfluorescent molecular gelator. The binary gels are fluorescent even at very low concentrations of the AIE chromophores, indicating that the rotation of their aromatic cores is restricted in the gel network. In tertiary gels, the fluorescence of the donor chromophore can be efficiently reduced by the acceptor chromophore through a combination of static and dynamic quenching process, via charge transfer from the donor to the acceptor. This work demonstrates a convenient approach to fabricate a supramolecular charge transfer system using an AIE donor and acceptor.

Rosmarinic acid protects on rat bone marrow mesenchymal stem cells from hydrogen peroxide-induced apoptosis.

To investigate the anti-oxidant activities and mechanism of rosmarinic acid (RA) on rat bone marrow mesenchymal stem cells (rBMSCs) from ischemia-induced apoptosis in vitro, which was established using H2O2-damage and analyzed for cell viability, cell apoptosis, ROS, morphological changes, and levels of apoptosis proteins. Pretreatment with RA significantly suppressed the generation of ROS, protected the morphological changes of cells, decrease the ratio of cell apoptosis, down-regulated the level of caspase-3, caspase-9, Bax/Bcl-2, and up-regulated the level of p-PI3K. These findings suggest that RA may protect rBMSCs from H2O2-induced apoptosis by partly regulating PI3K/Akt signaling pathway and can be developed as a potential anti-apoptotic agent for therapy in cardiovascular diseases.

Overexpressed HSPA2 correlates with tumor angiogenesis and unfavorable prognosis in pancreatic carcinoma.

Heat shock-related 70-kDa protein 2 (HSPA2) is known to correlate with tumor development and progression. This work aimed to determine the expression and prognostic roles of HSPA2 in pancreatic carcinoma. Tumor and their corresponding non-tumor tissues were obtained from 80 patients with pancreatic carcinoma. HSPA2 expression in tumor and non-tumor tissues was evaluated by immunohistochemistry. Expression of vascular endothelial growth factor (VEGF) and CD31 in tumor tissues were also evaluated by immunostaining. The relationships of HSPA2 with clinicopathological data, tumor angiogenesis and prognosis were analyzed. The results showed that HSPA2 expression was significantly elevated in tumor tissues compared with adjacent non-tumor tissues (P < 0.05). High HSPA2 expression was significantly associated with aggressive clinicopathological characteristics. HSPA2 staining was positively correlated with VEGF (r = 0.466, P < 0.001) and microvessel density (MVD) (r = 0.366, P = 0.001) in tumor tissues. Patients with high HSPA2 expression showed worse relapse-free survival (RFS) (P < 0.001) and overall survival (OS) (P < 0.001) than those with low HSPA2 expression. Multivariate analysis indicated that high HSPA2 expression was an independent predictor for poor RFS (P < 0.001) and OS (P = 0.001). Taken together, overexpressed HSPA2 is correlated with tumor angiogenesis and poor prognosis in pancreatic carcinoma. HSPA2 may play an important role in tumor progression, and serve as a potential biomarker for the prediction of adverse prognosis in pancreatic carcinoma.

Online restricted-access material combined with high-performance liquid chromatography and tandem mass spectrometry for the simultaneous determination of vanillin and its vanillic acid metabolite in human plasma.

An automated online solid-phase extraction with restricted-access material combined with high-performance liquid chromatography and tandem mass spectrometry was developed and validated for the simultaneous quantification of vanillin and its vanillic acid metabolite in human plasma. After protein precipitation by methanol, which contained the internal standards, the supernatant of plasma samples was injected to the system, the endogenous large molecules were flushed out, and target analytes were trapped and enriched on the adsorbent, resulting in a minimization of sample complexity and ion suppression effects. Calibration curves were linear over the concentrations of 5-1000 ng/mL for vanillin and 10-5000 ng/mL for vanillic acid with a coefficient of determination >0.999 for the determined compounds. The lower limits of quantification of vanillin and vanillic acid were 5.0 and 10.0 ng/mL, respectively. The intra- and inter-run precisions expressed as the relative standard deviation were 2.6-8.6 and 3.2-10.2%, respectively, and the accuracies expressed as the relative error were in the range of -6.1 to 7.3%. Extraction recoveries of analytes were between 89.5 and 97.4%. There was no notable matrix effect for any analyte concentration. The developed method was proved to be sensitive, repeatable, and accurate for the quantification of vanillin and its vanillic acid metabolite in human plasma.

Improved autophagic flux is correlated with mTOR activation in the later recovery stage of experimental acute pancreatitis.

BACKGROUND/OBJECTIVES: Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms. METHODS: AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity. RESULTS: AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury. CONCLUSIONS: Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.

Practical method for the rapid screening of xanthine oxidase inhibitors in herbal extracts by high-performance liquid chromatography based on on-line precolumn enzymatic reaction.

A high-performance liquid chromatography method with on-line precolumn enzymatic reaction for the screening of xanthine oxidase inhibitors in natural extracts was developed. In this method, the enzymatic reaction occurred at the capillary inlet during a predetermined waiting period, after which the reaction product, uric acid, was separated and detected by liquid chromatography using ultraviolet absorption at 295 nm. Enzyme inhibition can be read out directly from the reduced peak area of uric acid in comparison to a reference chromatogram obtained in the absence of any inhibitor. In the present study, the availability of on-line precolumn enzymatic reaction with ultraviolet detection was firstly evaluated by determining the inhibitory mechanism and IC50 values of allopurinol, a commercially available positive drug. Then, the newly developed method was applied to screening of ten natural extracts from traditional Chinese medicine and as a result, the extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim was found to be most positive for xanthine oxidase inhibition. The results obtained were compared with those obtained by offline enzyme assay and the effectiveness of the present method was confirmed. A rapid, low-cost, and fully automated method for xanthine oxidase inhibitor screening was proposed.

Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial.

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

Transparent cap adjusted the stent placed for stenosis after endoscopic injection of esophageal varices: A case report.

BACKGROUND: The stent embedded in the esophageal mucosa is one of the complications after stenting for esophageal stricture. We present a case of stent adjustment with the aid of a transparent cap after endoscopic injection of an esophageal varices stent. CASE SUMMARY: A 61-year-old male patient came to the hospital with discomfort of the chest after the stent implanted for the stenosis because of endoscopic injection of esophageal varices. The gastroscopy was performed, and the stent embedded into the esophageal mucosa. At first, we pulled the recycling line for shrinking the stent, however, the mucosa could not be removed from the stent. Then a forceps was performed to remove the mucosa in the stent, nevertheless, the bleeding form the mucosa was obvious. And then, we used a transparent cap to scrape the mucosa along the stent, and the mucosa were removed successfully without bleeding. CONCLUSION: A transparent cap helps gastroscopy to remove the mucosa embedded in the stent after endoscopic injection of the esophageal varices stent.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

Protective effects of edaravone on experimental chronic pancreatitis induced by dibutyltin dichloride in rats.

BACKGROUND/AIMS: To investigate the effects of edaravone, a potent free radical scavenger, on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and pancreatic fibrosis. METHODS: Male Sprague-Dawley rats were randomly divided into four groups (n = 16 each): control, DBTC, DBTC + edaravone, and control + edaravone. Edaravone or normal saline at a daily dose of 6 mg/kg body weight was given intraperitoneally from day 5 to day 28 after DBTC administration. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression of cytokines in pancreas TGF-ß, IL-6 and TNF was detected using RT-PCR. The activation of nuclear factor (NF)-κB in pancreatic tissue was evaluated by immunostaining and western-blot for NF-κB p65. α-smooth muscle actin (α-SMA) expression was also evaluated by immunostaining and western-blot to investigate the activation of pancreatic stellate cells (PSCs). RESULT: Edaravone treatment improved the rats' body weight (p < 0.01) and feed intake levels (p < 0.05), improved the histological scores and alleviated the fibrosis of pancreas samples (p < 0.05), as well as markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). The expression of cytokines TGF-ß, IL-6 and TNF in pancreas of DBTC group was also down-regulated by edaravone after treatment. Edaravone inhibited the activation of NF-κB and PSCs and exhibited protective effects on pancreatic tissue damage in CP. CONCLUSIONS: This antioxidant may be a promising therapeutic intervention for human CP.

A modified rat model of exercise-induced renal injury and the protective effects of losartan and yishen huanji decoction.

We modified a rat model of exercise-induced renal injury by forcing 4-week-old male Sprague-Dawley (SD) rats (the MOD group) running on a treadmill for 8 weeks under conditions of high temperature, high humidity, bearing weight with some additional stimulations. Compared with the control (CON) group, the traditional running group (TRA), the losartan potassium intervention running group (LOS) and the traditional Chinese medicine "Yishen Huanji Decoction" intervention running group (CHI), the urinary, biochemistry indicators, the concentrations of angiotensin II (Ang II) were significantly higher in the MOD group than in the TRA group. After 3--4 weeks and 8-week training program, the 24-h urine protein and NAG levels in the LOS group and CHI group were lower than in the MOD group respectively. The BUN and SCr levels in the CHI group were lower than in the MOD group and higher than in the LOS group. AngII concentrations in the LOS group were higher than the MOD group. The modified rat renal injury model induced greater lesions than the traditional model. High temperatures, humidity and weight bearing were critical factors to induce Ang II activation, which can aggravate renal injury. Losartan potassium and the "Yishen Huanji Decoction" can protect against renal injury.