Differential expression profiles and bioinformatics analysis of tRNA-derived small RNAs in epicardial fat of patients with atrial fibrillation.

The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly-CCC-003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.

The rhizomes of Atractylodes macrocephala relieve loperamide-induced constipation in rats by regulation of tryptophan metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is one of the most prevalent gastrointestinal tract diseases that seriously affects health-related quality of human life and requires effective treatments without side effect. The rhizome of Atractylodes macrocephala Koidz. (Compositae), called Atractylodes Macrocephala Rhizome (AMR), a commonly used traditional Chinese medicine, has been used to relieve the clinical symptoms of patients with constipation. AIM OF THE STUDY: To reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. MATERIALS AND METHODS: Loperamide-induced constipation rat model was established and the dose-dependent laxative effect of AMR was investigated. Untargeted metabolomics based on an UPLC-Q/TOF-MS technique combined with western blot analysis was used to explain the potential mechanism of AMR relieve loperamide-induced constipation in rats. RESULTS: The results showed that medium dose of AMR (AMR-M, 4.32 g raw herb/kg) and high dose of AMR (AMR-H, 8.64 g raw herb/kg) treatments significantly increased the fecal water content, Bristol score, gastrointestinal transit rate, and recovered the damaged colon tissues of constipated rats, but low dose of AMR (AMR-L, 2.16 g raw herb/kg) did not show laxative effect. Both AMR-M and AMR-H treatments also remarkably reduced the serum levels of vasoactive intestinal peptide (VIP), somatostatin (SS) and dopamine (DA), and increased the levels of motilin (MTL), gastrin (GAS) and 5-hydroxytryptamine (5-HT). Urine metabolomics revealed that constipation development was mainly ascribed to the perturbed tryptophan metabolism, and AMR-M and AMR-H markedly corrected the abnormal levels of five urine tryptophan metabolites, namely 4,6-dihydroxyquinoline, indole, 4,8-dihydroxyquinoline, 5-hydroxytryptamine, and kynurenic acid. Additionally, western blot analysis confirmed that the abnormal expression of rate-limiting enzyme involving in tryptophan metabolism, including tryptophan hydroxylase (TPH), monoamine oxidase (MAO) and indoleamine-2,3-dioxygenase (IDO) in the colon of constipated rats, were mediated by AMR-M and AMR-H. CONCLUSIONS: The findings provide insight into the mechanisms of STC and AMR could be developed as new therapeutic agent for prevention or healing of constipation.

Echocardiographic multiparameter assessment for patients with heart failure with preserved ejection fraction and atrial fibrillation.

We aimed to assess the echocardiographic parameters of cardiac structure and function in patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). Thirty-seven HFpEF patients with AF were selected, while 38 patients with simple HFpEF in the same period were selected as controls. Three-dimensional speckle-tracking echocardiography was performed on both groups and the parameters were compared. The early diastolic longitudinal peak strain rates [early diastolic longitudinal strain rate (LSRE), early diastolic circumferential strain rate (CSRE), early diastolic radial strain rate (RSRE) and early diastolic rotational strain rate (RotRE)], late diastolic longitudinal peak strain rates (LSRA, CSRA, RSRA and RotRA) and untwisting parameters [untwisting rate during isovolumic relaxation time (UTRIVR) and early peak untwisting rate (UTRE)] were all negatively correlated with the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity ( E/E') (p < 0.01). The cardiac event-free survival rate of the simple HFpEF group (92.11%) was significantly higher than that of the HFpEF + AF group (81.08%) (p < 0.0001). UTRIVR had a more significant correlation with E/E' ratio than the other indicators and could serve as a sensitive indicator for evaluating the diastolic function of patients with HFpEF + AF.

IMAGING MANIFESTATIONS OF WANDERING SPLEEN WITH TORSION.

BACKGROUND: A wandering spleen (WS) is a rare clinical entity characterized by a spleen located in the lower part of the abdomen or the pelvic cavity rather than the normal anatomical site. The complications of a wandering spleen include splenic torsion, splenic infarction, and adjacent visceral injury. CASE REPORT: We present a case of a male patient admitted to the emergency department with vomiting, nausea, and persistent lower abdominal pain. Computed tomography and ultrasound were performed and were used to diagnose a wandering spleen with torsion leading to splenic infarctions. Subsequently, laparoscopic surgery and pathology confirmed this diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ultrasound and computed tomography scans play a significant role in diagnosing WS and its complications, allowing an emergency physician to establish treatment options for WS.

Effects of probiotic administration on overweight or obese children: a meta-analysis and systematic review.

BACKGROUND: This paper aimed to examine the effects of probiotics on eight factors in overweight or obese children by meta-analysis, namely, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adiponectin, leptin and tumor necrosis factor-α (TNF-α) and summarize the mechanisms of action of probiotics based on the existing researches. METHODS: Six databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed and CNKI) were searched until March 2023. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model or random effect model to observe the effects of probiotic administration on the included indicators. RESULTS: Four publications with a total of 206 overweight or obesity children were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HDL-C (MD, 0.06; 95% CI 0.03, 0.09; P = 0.0001), LDL-C (MD, - 0.06; 95% CI - 0.12, - 0.00; P = 0.04), adiponectin (MD, 1.39; 95% CI 1.19, 1.59; P < 0.00001), leptin (MD, - 2.72; 95% CI - 2.9, - 2.54; P < 0.00001) and TNF-α (MD, - 4.91; 95% CI - 7.15, - 2.67; P < 0.0001) compared to those in the placebo group. Still, for BMI, the palcebo group seemed to be better than the probiotic group (MD, 0.85; 95% CI 0.04, 1.66; P = 0.04). TC (MD, - 0.05; 95% CI - 0.12, 0.02; P = 0.14) and TG (MD, - 0.16; 95% CI - 0.36, 0.05; P = 0.14) were not different between two groups. CONCLUSIONS: This review drew that probiotics might act as a role in regulating HDL-C, LDL-C, adiponectin, leptin and TNF-α in overweight or obesity children. Additionally, our systematic review yielded that probiotics might regulate lipid metabolism and improve obese associated symptoms by some paths. This meta-analysis has been registered at PROSPERO with ID: CRD42023408359.

Dioscin Ameliorates Experimental Autoimmune Thyroiditis via the mTOR and TLR4/NF-κB Signaling.

Background: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear. Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively. Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group. Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.

Electroacupuncture treatment ameliorates metabolic disorders in obese ZDF rats by regulating liver energy metabolism and gut microbiota.

Metabolic disorders represent a major therapeutic challenge to public health worldwide due to their dramatically increasing prevalence. Acupuncture is widely used as adjuvant therapy for multiple metabolic diseases. However, detailed biological interpretation of the acupuncture stimulations is still limited. The gut and the liver are intrinsically connected and related to metabolic function. Microbial metabolites might affect the gut-liver axis through multiple mechanisms. Liver metabolomics and 16S rRNA sequencing were used to explore the specific mechanism of electroacupuncture in treating ZDF rats in this study. Electroacupuncture effectively improved glycolipid metabolism disorders of the ZDF rats. Histopathology confirmed that electroacupuncture improved diffuse hepatic steatosis and hepatocyte vacuolation, and promoted glycogen accumulation in the liver. The treatment significantly improved microbial diversity and richness and upregulated beneficial bacteria that maintain intestinal epithelial homeostasis and decreased bacteria with detrimental metabolic features on host metabolism. Liver metabolomics showed that the main effects of electroacupuncture include reducing the carbon flow and intermediate products in the TCA cycle, regulating the metabolism of various amino acids, and inhibiting hepatic glucose output and de novo lipogenesis. The gut-liver axis correlation analysis showed a strong correlation between the liver metabolites and the gut microbiota, especially allantoin and Adlercreutzia. Electroacupuncture treatment can improve abnormal energy metabolism by reducing oxidative stress, ectopic fat deposition, and altering metabolic fluxes. Our results will help us to further understand the specific mechanism of electroacupuncture in the treatment of metabolic diseases.

[Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology].

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

Eudesmane-type sesquiterpenes from the rhizomes of Atractylodes macrocephala and their bioactivities.

Fifteen undescribed eudesmane-type sesquiterpenes, named atramacronoids D-R, along with fourteen known analogues were isolated from the rhizomes of Atractylodes macrocephala. The structures of atramacronoids D-R were elucidated based on extensive spectroscopic data analysis, Snatzke's rule, electronic circular dichroism (ECD) calculations, and X-ray crystallographic analysis. Notably, of the undescribed isolates, atramacronoids D and E are the first example of eudesmanolactam-phenol and eudesmanolactam-ethyl hybrids obtained from plants, respectively. A pair of enantiomers, (+)- and (-)-atramacronoids F, were successfully resolved by chiral-phase HPLC. Atramacronoid D exhibited weak cytotoxicity against SGC-7901 cells. Atramacronoid E significantly promoted the proliferation of LPS-induced IEC-6 cells.

Ultrasonographic manifestations and misdiagnosis analysis of ovarian leiomyoma.

Objectives: Ovarian leiomyomas (OLs) are rare and account for only 0.5 to 1% of benign ovarian tumors. This study investigated the ultrasonographic manifestations of OL and the potential reasons for misdiagnosis. Methods: Between July 2018 and July 2023, 7 patients diagnosed with OL by surgical pathology and immunohistochemistry were enrolled in this retrospective analysis. Ultrasound (US) examinations were performed before surgery. Clinical characteristics, pathological findings, ultrasonographic manifestations, and treatment were reviewed. Results: The mean age of the 7 patients was 39.0 ± 11.57 years, with a disease course of 0.1 to 24 months. All ovarian leiomyomas were unilateral. Four cases occurred in the right ovary, and three cases occurred in the left ovary. All lesions presented as hypoechogenic, well-circumscribed, round or oval in shape, and regular in morphology. No significant blood flow signal was detected peripheral to or inside the mass in 3 cases (42.8%), and a minimal flow signal was detected peripheral to or inside the mass in 4 cases (58.2%). A total of 7 ultrasonographic images of OL were misdiagnosed: 1 patient was misdiagnosed with subserosal uterine leiomyoma, and 6 patients were misdiagnosed with a tumor in the ovarian thecoma-fibroma group. Conclusion: The imaging manifestation of OL lacks specificity; thus, preoperatively distinguishing OL from other ovarian tumors and subserosal uterine leiomyomas is difficult. Immunohistochemistry may be helpful for the definitive diagnosis of OL. The possibility of ovarian leiomyoma should be considered in patients with uterine leiomyomas coexisting with an adnexal ovarian solid mass.

Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver.

BACKGROUND: The rising global incidence of type 2 diabetes mellitus (T2DM) highlights a need for new therapies. The Zishen Pill (ZSP) is a traditional Chinese herbal decoction that has previously shown hypoglycemic effects in C57BL/KsJ-db/db mice, although the therapeutic mechanism remains unknown. This study aims to explore the underlying mechanisms of ZSP's hypoglycemic effects using db/db mice. METHODS: Db/db mice were divided into two groups: model group and ZSP group, while wt/wt mice were used as a normal control. ZSP was given to mice by gavage for 40 days. During treatment, blood glucose level and body weight were monitored continuously. Oral glucose tolerance test (OGTT) was performed at day 35. Blood and tissue samples were collected at the end of treatment for further analyses. Mice liver samples were analyzed with mRNA transcriptomics using functional annotation and pathway enrichment to identify potential mechanisms that were then explored with qPCR and Western Blot techniques. RESULTS: ZSP treatment significantly reduced weight gain and glycemic severity in db/db mice. ZSP also partially restored the glucose homeostasis in db/db mice and increased the hepatic glycogen content. Transcriptomic analyses showed ZSP increased expression of genes involved in glycolysis including Hk2, Hk3, Gck and Pfkb1, and decreased expression of G6pase. Additionally, the gene and protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and Csf1 and Flt3 mRNA expression were significantly upregulated in ZSP group. CONCLUSION: ZSP treatment reduced the severity of diabetic symptoms in db/db mice. ZSP increased expression of genes associated with glycogen synthesis and glycolysis, and decreased gluconeogenesis via the enhancement of the PI3K/AKT signaling in the liver.

The effects of probiotic administration on patients with prediabetes: a meta-analysis and systematic review.

BACKGROUND: This paper aimed to examine the effects of probiotics on eight factors in the prediabetic population by meta-analysis, namely, fasting blood glucose (FBG), glycated haemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the mechanisms of action are summarized from the existing studies. METHODS: Seven databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Med) were searched until March 2022. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model to observe the efficacy of probiotic supplementation on the included indicators. RESULTS: Seven publications with a total of 460 patients were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HbA1c (WMD, -0.07; 95% CI -0.11, -0.03; P = 0.001), QUICKI (WMD, 0.01; 95% CI 0.00, 0.02; P = 0.04), TC (SMD, -0.28; 95% CI -0.53, -0.22; P = 0.03), TG (SMD, -0.26; 95% CI -0.52, -0.01; P = 0.04), and LDL-C (WMD, -8.94; 95% CI -14.91, -2.97; P = 0.003) compared to levels in the placebo group. The effects on FBG (WMD, -0.53; 95% CI -2.31, 1.25; P = 0.56), HOMA-IR (WMD, -0.21; 95% CI -0.45, 0.04; P = 0.10), and HDL-C (WMD, 2.05; 95% CI -0.28, 4.38; P = 0.08) were not different from those of the placebo group. CONCLUSION: The present study clearly indicated that probiotics may fulfil an important role in the regulation of HbA1c, QUICKI, TC, TG and LDL-C in patients with prediabetes. In addition, based on existing studies, we concluded that probiotics may regulate blood glucose homeostasis in a variety of ways. TRIAL REGISTRATION: This meta-analysis has been registered at PROSPERO with ID: CRD42022321995.

TangNaiKang, herbal formulation, alleviates obesity in diabetic SHR/cp rats through modulation of gut microbiota and related metabolic functions.

CONTEXT: Tangnaikang (TNK) is a Chinese herbal formulation that has lipid-lowering effects, but its effect on reducing obesity has not been studied. OBJECTIVE: To observe the effect of TNK on obesity and explore its effect on gut microbiota of obese rats. MATERIALS AND METHODS: The SHR/NDmcr-cp rats were divided into three groups: (1) 3.24 g/kg TNK (High TNK), (2) 1.62 g/kg TNK (Low TNK), and (3) an untreated control (CON). Wistar-Kyoto rats were used as normal controls (WKY). After 8 weeks of TNK oral administration, body weight, abdominal circumference, triglycerides (TC) and total cholesterol (CHO) were measured. Gut microbiota diversity was studied by 16S rDNA sequencing, and metagenomes analysis was conducted to determine alteration in functional gene expression. RESULTS: The body weight (496.60 ± 6.0 g vs. 523.40 ± 5.6 g), abdomen circumference (24.00 ± 0.11 cm vs. 24.87 ± 0.25 cm), TC (3.04 ± 0.16 mmol/L vs. 4.97 ± 0.21 mmol/L), CHO (2.42 ± 0.15 mmol/L vs. 2.84 ± 0.09 mmol/L) of rats in the High TNK group were decreased significantly (all p < 0.05). TNK administration regulates intestinal flora, up-regulates Eisenbergiella and down-regulates Clostridium_sensu_stricto_1, which is beneficial to the production of short-chain fatty acids (SCFAs). Metagenomes analysis shows that TNK is closely related to the fatty acid synthesis pathway. DISCUSSION AND CONCLUSIONS: TNK can regulate gut microbiota to reduce obesity, which may be related to fatty acid metabolism. Our research supports the clinical application of TNK preparation and provides a new perspective for the treatment of obesity.

A Retrospective Study of Diaphragmatic Breathing Training Combined with Discharge Care Bundles in Patients with Chronic Obstructive Pulmonary Disease.

Objective: Both physical exercise and discharge care bundles can improve patient outcomes and reduce hospitalization rates among subjects with chronic obstructive pulmonary disease (COPD). The retrospective analysis aims to determine the advantages of care bundles combined with diaphragmatic breathing training (DBT) in COPD patients after discharge. Methods: Of the 110 COPD patients, 55 patients received DBT alone (DBT group) and 55 participants received the combined intervention (care bundle + DBT group). Three months after discharge, we assessed the outcomes of patients using Bristol COPD Knowledge Questionnaire (BCKQ), Hospital Anxiety and Depression Scale (HADS), COPD Assessment Test (CAT), and St. George's Respiratory Questionnaire (SGRQ). Meanwhile, COPD-related hospital readmissions were also recorded. Results: The BCKQ score for assessing the disease knowledge level was increased in patients at 3 months after the combined interventions as compared to the baseline values, which was higher in the care bundle + DBT group than the DBT group at 3 months. Moreover, improvements in negative emotion and clinical symptoms from baseline to 3-month follow-up were seen in both the two groups. Besides, the care bundle + DBT group showed the mitigation of depression and anxiety and the alleviation of clinical symptoms in comparison with the DBT group at 3 months. Participants who received combined interventions had lower SGRQ scores than those who received DBT alone. The time to first COPD-related readmission was shorter for patients in the care bundle + DBT group compared with the DBT group. Conclusions: DBT combined with discharge care bundles for COPD patients resulted in improvements in disease-specific knowledge, negative emotions, and clinical symptoms with better HRQOL and lower readmission rate.

Nomograms predicting the overall and cancer-specific survival of patients with buccal mucosa cancer.

OBJECTIVES: To construct predictive models for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with buccal mucosa cancer (BMC). STUDY DESIGN: Data of 936 patients with BMC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Nomograms were constructed based on multivariate Cox regression analyses, and validated using calibration plots, time-dependent receiver operating characteristic curves, and decision curve analyses. RESULTS: Age at diagnosis, marital status, grade, histopathology, SEER stage, tumor size, and surgery were associated with OS, whereas age at diagnosis, grade, histopathology, SEER stage, tumor size, and surgery were associated with CSS (all P < .05). The concordance indexes for OS and CSS were 0.79 and 0.80 in the training cohort, respectively, and those in the validation cohort were 0.78 and 0.80. Time-dependent receiver operating characteristic curves showed great predictability in nomograms. Decision curve analyses demonstrated good clinical value for OS (4%-88%) and CSS (3%-77%) nomograms. Patients were stratified into 3 risk groups, with the worst prognosis in the high-risk subgroup (P < .001). CONCLUSIONS: We developed and validated 2 nomograms predicting OS and CSS and established the corresponding risk classification systems in patients with BMC. These models assisted in precise administration of individual therapeutic regimens.

Single-Cell Transcriptomics Uncovers Cellular Heterogeneity, Mechanisms, and Therapeutic Targets for Parkinson's Disease.

Objective: This study aimed to exploit cellular heterogeneity for revealing mechanisms and identifying therapeutic targets for Parkinson's disease (PD) via single-cell transcriptomics. Methods: Single-cell RNA sequencing (scRNA-seq) data on midbrain specimens from PD and healthy individuals were obtained from the GSE157783 dataset. After quality control and preprocessing, the principal component analysis (PCA) was presented. Cells were clustered with the Seurat package. Cell clusters were labeled by matching marker genes and annotations of the brain in the CellMarker database. The ligand-receptor networks were established, and the core cell cluster was selected. Biological functions of differentially expressed genes in core cell clusters were analyzed. Upregulated marker genes were identified between PD and healthy individuals, which were measured in 18 PD patients' and 18 healthy individuals' blood specimens through RT-qPCR and Western blotting. Results: The first nine PCs were determined, which can better represent the overall change. Five cell clusters were identified, including oligodendrocytes, astrocytes, neurons, microglial cells, and endothelial cells. Among them, endothelial cells were the core cell cluster in the ligand-receptor network. Marker genes of endothelial cells possessed various biological functions. Among them, five marker genes (ANGPT2, APOD, HSP90AA1, HSPA1A, and PDE1C) were upregulated in PD patients' than in healthy individuals' endothelial cells, which were confirmed in PD patients' than in healthy individuals' blood specimens. Conclusion: Our findings revealed that the cellular heterogeneity of PD and endothelial cells could play a major role in cell-to-cell communications. Five upregulated marker genes of endothelial cells could be underlying therapeutic targets of PD, which deserve more in-depth clinical research.

Quality markers of Baizhu dispensing granules based on multi-component qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The dispensing granules of traditional Chinese medicines (TCMs) is an innovative form of medicinal material for TCMs decoction, which is gradually recognized in the clinic due to being suitable for production on a large scale and convenient to take for patients. However, the quality control of TCMs dispensing granules is being challenged, because they contain too many unrevealed hydrophilic components. AIM OF THE STUDY: Here, the dispensing granules produced from the rhizome of Atractylodes macrocephala (Baizhu dispensing granules), were explored as a case to explore the quality markers correlated to the clinical efficacy of TCMs dispensing granules by a comprehensive strategy of integrating chemical profiling, network pharmacology, and chemometric analysis. MATERIALS AND METHODS: First, the chemical profiling of Baizhu dispensing granules was characterized by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Subsequently, the potential active components responsible for the efficacy of Baizhu dispensing granules were screened via network pharmacology, and the ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was developed for quantitative analysis of the potential active components in 26 batches of Baizhu dispensing granules. Finally, the quality markers of Baizhu dispensing granules were deciphered based on content variations of potential active components and chemometric analysis. RESULTS: A total of 69 components were identified from Baizhu dispensing granules. Network pharmacology analysis further revealed that eight of them including five caffeoylquinic acids (31, 32, 36, 42, 44) and three sesquiterpenoids (63, 67, 76) were intimately connected to the core targets of dyspepsia, enteritis, gastritis and immunity. The contents of eight components differed greatly among 26 batches of Baizhu dispensing granules. Chlorogenic acid (31), cryptochlorogenic acid (32) and atractylenolide III (63) have higher concentrations and make great contributions to distinguish different batches of the Baizhu dispensing granules based on principal component analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA), and could be used as the quality markers of Baizhu dispensing granules. CONCLUSIONS: Our study defined the quality markers of Baizhu dispensing granules, which will benefit further investigation on the quality evaluation of TCMs dispensing granules containing Baizhu. The strategy used in this study will be helpful for discovering the quality markers of other TCMs dispensing granules.

Diosgenin reduces phosphodiesterase 3B (PDE3B) through AMP-activated protein kinase/ mechanistic target of rapamycin (AMPK/mTOR) signaling pathway to ameliorate streptozotocin-induced pancreatic ß-cell apoptosis and dysfunction.

Diabetes mellitus is a metabolic disease caused by defective insulin secretion and/or insulin action. And insulin is the main hormone released by the pancreatic ß-cells. Diosgenin (DG) is a phytochemical with pharmacological activity that increases insulin secretion in streptozotocin (STZ)-induced pancreatic ß-cells of diabetic rats. In this paper, we investigated the effect and mechanism of DG on cell apoptosis and dysfunction in STZ-induced pancreatic ß-cells. Cell viability was detected by CCK-8, apoptosis by flow cytometry, and apoptosis-related protein expression by Western blot. Western blot and RT-qPCR were performed to detect the expression of related genes. The results showed that in STZ-induced INS-1 cells, DG could improve cell viability, inhibit apoptosis, attenuate oxidative stress levels and increase insulin secretion. Notably, PDE3B was highly expressed in STZ-induced INS-1 cells, while DG could significantly inhibit PDE3B expression in a dose-dependent manner. More importantly, overexpression PDE3B remarkably reversed the effect of DG on STZ-induced INS-1 cells. It is thus clear that DG might inhibit STZ-treated pancreatic ß-cell apoptosis and reduce dysfunction via downregulating PDE3B, which provided a more reliable theoretical basis for the treatment of diabetes mellitus with DG.

Exploring the role of Tibetan medicinal formula Qishiwei Zhenzhu Pills (Ranasampel) against diabetes mellitus-linked cognitive impairment of db/db mice through serum pharmacochemistry and microarray data analysis.

Background: Diabetes cognitive impairment (DCI) is a common diabetic central nervous system disorder that severely affects the quality of life of patients. Qishiwei Zhenzhu Pills (Ranasampel) is a valuable Tibetan medicine formula with the ability to improve cerebral blood vessels, protect nerves and improve learning and memory, which has also been widely verified in clinical and basic research. Currently, the prevention and treatment of DCI are still in the exploratory research stage, and the use of Ranasampel will provide new ideas and insights for its treatment. Objective: This study is to explore the absorbed components in serum derived from Ranasampel using serum pharmacochemistry, then identify the potential mechanism of Ranasampel for the treatment of DCI through bioinformatics and microarray data validation. Methods: The UPLC-Q-Exactive MS/MS-based serum pharmacochemistry method was conducted to identify the main active components in serum containing Ranasampel. Then, these components were used to predict the possible biological targets of Ranasampel and explore the potential targets in treating DCI by overlapping with differentially expressed genes (DEGs) screened from Gene Expression Omnibus datasets. Afterward, the protein-protein interaction network, enrichment analyses, hub gene identification, and co-expression analysis were used to study the potential mechanism of Ranasampel. Particularly, the hub genes and co-expression transcription factors were further validated using hippocampal expression profiles of db/db mice treated with Ranasampel, while the Morris water-maze test and H&E staining were used to assess the spatial learning and memory behaviors and histopathological changes. Results: Totally, 40 compounds derived from Ranasampel had been identified by serum sample analysis, and 477 genes related to these identified compounds in Ranasampel, 110 overlapping genes were collected by the intersection of Ranasampel target genes and DEGs. Further comprehensive analysis and verification emphasized that the mechanism of Ranasampel treatment of DCI may be related to the improvement of learning and memory function as well as insulin resistance, hyperglycemia-induced neuronal damage, and neuroinflammation. Conclusion: This study provided useful strategies to explore the potential material basis for compound prescriptions such as Ranasampel. These hub genes and common pathways also provided new ideas for further study of therapeutic targets of DCI and the pharmacological mechanism of Ranasampel.

Models to assess imported cases on the rebound of COVID-19 and design a long-term border control strategy in Heilongjiang Province, China.

Since the outbreak of COVID-19 in Wuhan, China in December 2019, it has spread quickly and become a global pandemic. While the epidemic has been contained well in China due to unprecedented public health interventions, it is still raging or not yet been restrained in some neighboring countries. Chinese government adopted a strict policy of immigration diversion in major entry ports, and it makes Suifenhe port in Heilongjiang Province undertook more importing population. It is essential to understand how imported cases and other key factors of screening affect the epidemic rebound and its mitigation in Heilongjiang Province. Thus we proposed a time switching dynamical system to explore and mimic the disease transmission in three time stages considering importation and control. Cross validation of parameter estimations was carried out to improve the credibility of estimations by fitting the model with eight time series of cumulative numbers simultaneous. Simulation of the dynamics shows that illegal imported cases and imperfect protection in hospitals are the main reasons for the second epidemic wave, the actual border control intensities in the province are relatively effective in early stage. However, a long-term border closure may cause a paradox phenomenon such that it is much harder to restrain the epidemic. Hence it is essential to design an effective border reopening strategy for long-term border control by balancing the limited resources on hotel rooms for quarantine and hospital beds. Our results can be helpful for public health to design border control strategies to suppress COVID-19 transmission.