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Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.
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Background: The beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis. Methods: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson's staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing. Results: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice. Conclusion: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.
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Bacterial infection is one of the major causes of neonatal morbidity and mortality worldwide. Finding rapid and reliable methods for early recognition and diagnosis of bacterial infections and early individualization of antibacterial drug administration are essential to eradicate these infections and prevent serious complications. However, this is often difficult to perform due to non-specific clinical presentations, low accuracy of current diagnostic methods, and limited knowledge of neonatal pharmacokinetics. Although neonatal medicine has been relatively late to embrace the benefits of machine learning (ML), there have been some initial applications of ML for the early prediction of neonatal sepsis and individualization of antibiotics. This article provides a brief introduction to ML and discusses the current state of the art in diagnosing and treating neonatal bacterial infections, gaps, potential uses of ML, and future directions to address the limitations of current studies. Neonatal bacterial infections involve a combination of physiologic development, disease expression, and treatment response outcomes. To address this complex relationship, future models could consider appropriate ML algorithms to capture time series features while integrating influences from the host, microbes, and drugs to optimize antimicrobial drug use in neonates. All models require prospective clinical trials to validate their clinical utility before clinical use.
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Anti-Bacterial Agents , Bacterial Infections , Machine Learning , Humans , Infant, Newborn , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/diagnosis , Clinical Decision-Making , Neonatal Sepsis/drug therapy , Neonatal Sepsis/diagnosisABSTRACT
The challenges of drug development in pediatric, pregnant and geriatric populations are a worldwide concern shared by regulatory authorities, pharmaceutical companies, and healthcare professionals. Model-informed drug development (MIDD) can integrate and quantify real-world data of physiology, pharmacology, and disease processes by using modeling and simulation techniques to facilitate decision-making in drug development. In this article, we reviewed current MIDD policy updates, reflected on the integrity of physiological data used for MIDD and the effects of physiological changes on the drug PK, as well as summarized current MIDD strategies and applications, so as to present the state of the art of MIDD in pediatric, pregnant and geriatric populations. Some considerations are put forth for the future improvements of MIDD including refining regulatory considerations, improving the integrity of physiological data, applying the emerging technologies, and exploring the application of MIDD in new therapies like gene therapies for special populations.
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Drug Development , Humans , Drug Development/methods , Pregnancy , Female , Child , Aged , Models, BiologicalABSTRACT
OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.
Subject(s)
Apoptosis , Cell Proliferation , Colorectal Neoplasms , Cyclin-Dependent Kinase Inhibitor p21 , Drugs, Chinese Herbal , Mice, Inbred BALB C , Mice, Nude , Signal Transduction , Tumor Suppressor Protein p53 , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/drug therapy , Tumor Suppressor Protein p53/metabolism , Cell Proliferation/drug effects , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Animals , Signal Transduction/drug effects , Apoptosis/drug effects , Drugs, Chinese Herbal/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Cell Line, Tumor , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Xenograft Model Antitumor Assays , Mice , HCT116 Cells , Down-Regulation/drug effectsABSTRACT
INTRODUCTION: Older individuals face an elevated risk of developing bacterial infections. The optimal use of antibacterial agents in this population is challenging because of age-related physiological alterations, changes in pharmacokinetics (PK) and pharmacodynamics (PD), and the presence of multiple underlying diseases. Therefore, population pharmacokinetics (PPK) studies are of great importance for optimizing individual treatments and prompt identification of potential risk factors. AREA COVERED: Our search involved keywords such as 'elderly,' 'old people,' and 'geriatric,' combined with 'population pharmacokinetics' and 'antibacterial agents.' This comprehensive search yielded 11 categories encompassing 28 antibacterial drugs, including vancomycin, ceftriaxone, meropenem, and linezolid. Out of 127 studies identified, 26 (20.5%) were associated with vancomycin, 14 (11%) with meropenem, and 14 (11%) with piperacillin. Other antibacterial agents were administered less frequently. EXPERT OPINION: PPK studies are invaluable for elucidating the characteristics and relevant factors affecting the PK of antibacterial agents in the older population. Further research is warranted to develop and validate PPK models for antibacterial agents in this vulnerable population.
Subject(s)
Anti-Bacterial Agents , Humans , Anti-Bacterial Agents/pharmacokinetics , Bacterial Infections/drug therapy , Meropenem , Risk Factors , VancomycinABSTRACT
Patients who receive allogeneic haematopoietic stem cell transplantation (allo-HSCT) may develop sepsis, which result in a highly intensive care unit admission rate and mortality. Therefore, short-term and long-term prognostic models for sepsis after allo-HSCT are urgently needed. We enrolled patients receiving allo-HSCT who developed sepsis after allo-HSCT at Peking University People's Hospital between 2012 and 2021, including 287 patients who received allo-HSCT in 2018-2021 in the derivation cohort, and 337 patients in 2012-2017 in the validation cohort. Multivariate logistic regression analysis was used to identify prognostic factors, and these identified factors were incorporated into two scoring models. Seven independent factors (acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD), total bilirubin, lactate dehydrogenase (LDH) and organ dysfunction [renal, lung and heart]) were included in the 6-month prognostic model, and six factors (cGVHD, C-reactive protein, LDH, organ dysfunction [lung, neurologic and coagulation]) were included in the 14-day prognostic model. The area under the receiver operating characteristic curves, calibration plots and decision curve analysis demonstrated the robust predictive performance of the models, better than the Sequential Organ Failure Assessment score. Early identification of patients with high risk of 6-month and 14-day death may allow clinicians to provide timely treatments and improve the therapeutic effects.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Sepsis , Humans , Multiple Organ Failure/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Sepsis/etiology , Prognosis , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Retrospective StudiesABSTRACT
Background and aim: Hepatitis C virus infection can lead to an enormous health burden worldwide. Investigating the changes in HCV-related burden between different countries could provide inferences for disease management. Hence, we aim to explore the temporal tendency of the disease burden associated with HCV infection in China, India, the United States, and the world. Methods: Detailed data on the total burden of disease related to HCV infection were collected from the Global Burden of Disease (GBD) 2019 database. Joinpoint regression models were used to simulate the optimal joinpoints of annual percent changes (APCs). Further analysis of the age composition of each index over time and the relationship between ASRs and the socio-demographic Index (SDI) were explored. Finally, three factors (population growth, population aging, and age-specific changes) were deconstructed for the changes in the number of incidences, deaths, and DALYs. Results: It was estimated that 6.2 million new HCV infections, 0.54 million HCV-related deaths, and 15.3 million DALYs worldwide in 2019, with an increase of 25.4, 59.1, and 43.6%, respectively, from 1990, are mainly due to population growth and aging. China experienced a sharp drop in age-standardized rates in 2019, the United States showed an upward trend, and India exhibited a fluctuating tendency in the burden of disease. The incidence was increasing in all locations recently. Conclusion: HCV remains a global health concern despite tremendous progress being made. The disease burden in China improved significantly, while the burden in the United States was deteriorating, with new infections increasing recently, suggesting more targeted interventions to be established to realize the 2030 elimination goals.
Subject(s)
Hepacivirus , Hepatitis C , Humans , United States/epidemiology , Quality-Adjusted Life Years , Hepatitis C/epidemiology , India/epidemiology , China/epidemiologyABSTRACT
Background: Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. Dysbiosis of gut microbiome has been identified as one of the key environmental factors contributing to NAFLD. As an essential nutrition, Vitamin D (VD) plays an important role in regulating gut microbiota based on its receptor (Vitamin D Receptor, VDR) which is highly expressed in the gastrointestinal tract. Methods: Rats were fed with HFD (high-fat diet) for 12 weeks. And the rats were treated with VD two times a week by intraperitoneal injection for 12 weeks. H&E staining combined with plasma biochemical index was performed to characterize pathological changes and function of the liver. Fecal microbiota 16S rRNA gene sequencing and metabolomics were taken to reveal the altered gut microbiota and metabolites. Result: The VD alleviates the HFD-induced lipid accumulation in the liver as well as decreases the levels of amlodipine besylate (ALT) and amlodipine aspartate (AST). VD supplement decreased the ratio of phylum Firmicutes/Bacteroidetes (F/B) but increased alpha diversity. In addition, the VD treatment improved the HFD-induced gut microbiota by increasing the Prevotella and Porphyromonadaceae and decreasing Mucispirillum, Acetatifactor, Desulfovibrio, and Oscillospira abundance. Furthermore, the capability of tyrosine metabolism, tryptophan metabolism, arginine biosynthesis, and sphingolipid metabolism was enhanced after VD treatment. Consistently, Prevotella positively correlated with tryptophan metabolism and sphingolipid metabolism. Importantly, the Prevotella abundance was positively associated with serotonin, melatonin, tryptamine, L-arginine, and 3-dehydrosphinganine which synthesize from tryptophan, tyrosine, arginosuccinate, and serine, respectively. Conclusion: VD treatment inhibited HFD-induced NAFLD accompany by dysbiosis gut microbiota and metabolites, suggesting that VD supplement could be a potential intervention used for NAFLD treatment by targeting the specific microbiota.
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Background: Obesity has become a global health and socioeconomic problem because of an inadequate balance between energy intake and energy expenditure. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most commonly used strategies for weight loss, which have been proven to benefit from gut microbiota restoration. Methods: Rats received SG, RYGB, and sham operations for 10 weeks. At the end of the experiment, the fecal microbiota was analyzed using 16s rRNA gene sequencing. In addition, the shift in the plasma metabolism of rats that underwent RYGB surgery was analyzed using untargeted metabolomics. The crosstalk between microbiome and metabolites was revealed using metabolic pathway enrichment and integrated analysis. Result: The SG surgery induced a modest shift in the gut microbiota relative to the RYGB. RYGB significantly decreased the alpha diversity and Firmicutes/Bacteroides (F/B) ratio and increased the proportion of Escherichia, Bacteroides, and Akkermansia genera compared to sham and SG operations. The predicted function of gut microbiota revealed that the RYGB surgery uniquely enhanced the capability of linoleic acid and sphingolipid metabolism. Furthermore, the circulating serine, phosphatidylcholine (PC) 20:5/22:5, riboflavin, L-carnitine, and linoleic acid were evaluated after RYGB surgery. In addition, the metabolic pathway enrichment and integrated analysis suggest that the RYGB induced Escherichia, Bacteroides, and Akkermansia might inhibit the sphingonine and phytosphingosine metabolisms from serine and promote the PC (20:5/22:5) metabolism to produce linoleic acid. Conclusion: This comprehensive analysis not only revealed the difference in the gut microbiota shifts after SG and RYGB but also discovered the perturbative changes in microbial communities and metabolic pathways after RYGB surgery, which provided clues for improving the beneficial effect of RYGB in metabolic disease intervention via regulating bacterial-metabolite crosstalk.
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BACKGROUND & AIMS: The interplay among dietary intake, gut microbiota, gut metabolites and circulating metabolites in adolescents is barely known, not to mention sex-dependent pattern. We aimed to explore unique profiles of gut bacterial, gut metabolites and circulating metabolites from both genders of adolescents due to BMI and eating pattern. METHODS: Clinical indices, fecal gut microbiota, fecal and plasma metabolites, and diet intake information were collected in case-control sample matched for normal and obesity in girls (normal = 12, obesity = 12) and boys (normal = 20, obesity = 20), respectively. 16S rRNA gene sequencing and untargeted metabolomics was performed to analysis the signature of gut microbiota and metabolites. Unique profiles of girls associated with BMI and eating pattern was revealed by Spearman's correlations analysis, co-occurrence network analysis, Kruskal-Wallis test, and Wilcoxon rank-sum test. RESULTS: Gender difference was found between normal and obese adolescents in gut microbiota, fecal metabolites, and plasma metabolites. The Parabacteroides were only decreased in obese girls. And the characteristic of obese girls' and boys' cases in fecal and plasma was xanthine and glutamine, ornithine and LCA, respectively. Soy products intake was negatively associated with Parabacteroides. The predicted model has a higher accuracy based on the combined markers in obesity boys (AUC = 0.97) and girls (AUC = 0.97), respectively. CONCLUSIONS: Reduced abundance of Phascolarctobacterium and Parabacteroides, as well as the increased fecal xanthine and ornithine, may provide a novel biomarker signature in obesity girls and boys. Soy products intake was positively and negatively associated with Romboutsia and Parabacteroides abundance, respectively. And the combined markers facilitate the accuracy of predicting obesity in girls and boys in advance.
Subject(s)
Gastrointestinal Microbiome , Pediatric Obesity , Adolescent , Humans , Female , Male , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S , Feces/microbiology , Metabolome , Eating , Biomarkers , Ornithine , XanthinesABSTRACT
Endometrial cancer (EC) is the most prevalent gynecological malignancy, with a higher risk in obese woman, indicating the possibility of gut microbiota involvement in EC progression. However, no direct evidence of a relationship between EC and gut microbiota in humans has been discovered. Here, we performed 16S rRNA sequencing to explore the relationship between dysbiosis of gut microbiota and cancer development in different types of EC patients. The results clearly show the differential profiles of gut microbiota between EC patients and normal participants as well as the association between gut microbiota and EC progression. Targeted metabolomics of plasma revealed an increased level of C16:1 and C20:2, which was positively associated with the abundance of Ruminococcus sp. N15.MGS-57. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects not only was positively associated with blood C16:1 and C20:2 but also was negatively correlated with betalain and indole alkaloid biosynthesis. Furthermore, the combined marker panel of gut bacteria, blood metabolites, and clinical indices could distinguish the EC patients under lean and overweight conditions from normal subjects with high accuracy in both discovery and validation sets. In addition, the alteration of tumor microenvironment metabolism of EC was characterized by imaging mass microscopy. Spatial visualization of fatty acids showed that C16:1 and C18:1 obviously accumulate in tumor tissue, and C16:1 may promote EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1 in EC tissues, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment. IMPORTANCE A growing number of studies have shown the connection between gut microbiota, obesity, and cancer. However, to our knowledge, the association between gut microbiota and endometrial cancer progression in humans has not been studied. We recruited EC and control individuals as research participants and further subgrouped subjects by body mass index to examine the association between gut microbiota, metabolites, and clinical indices. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects was not only positively associated with blood C16:1 but also negatively correlated with betalain and indole alkaloid biosynthesis. Spatial visualization of fatty acids by imaging mass microscopy showed that C16:1 obviously accumulates in tumor tissue, and C16:1 may promote the EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment.
Subject(s)
Endometrial Neoplasms , Gastrointestinal Microbiome , Female , Humans , RNA, Ribosomal, 16S/genetics , Obesity/microbiology , Feces/microbiology , Biomarkers , Fatty Acids , Indole Alkaloids , TOR Serine-Threonine Kinases , Tumor MicroenvironmentABSTRACT
Branched-chain amino acids (BCAAs), composed of leucine, isoleucine, and valine, are important essential amino acids in human physiology. Decades of studies have revealed their roles in protein synthesis, regulating neurotransmitter synthesis, and the mechanistic target of rapamycin (mTOR). BCAAs are found to be related to many metabolic disorders, such as insulin resistance, obesity, and heart failure. Also, many diseases are related to the alteration of the BCAA catabolism enzyme branched-chain α-keto acid dehydrogenase kinase (BCKDK), including maple syrup urine disease, human autism with epilepsy, and so on. In this review, diseases and the corresponding therapies are discussed after the introduction of the catabolism and detection methods of BCAAs and BCKDK. Also, the interaction between microbiota and BCAAs is highlighted.
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Deoxynivalenol (DON) is a secondary metabolite of fungi. Ingestion of feed containing DON causes severe intestinal damage in humans and animals, possibly due to cholesterol-enriched lipid raft abnormalities. Cholic acid (CA) and lithocholic acid (LCA) are metabolites of cholesterol transformation, which have been proven to benefit epithelial cell proliferation and reduce intestinal inflammation and lesions. Therefore, we aimed to study the protective roles of CA and LCA administration on the DON-exposed intestinal epithelial cells (IPI-2I) and the underlying mechanisms involved in cholesterol metabolism. We found that LCA pretreatment, but not CA, alleviated the reduction of cell numbers caused by DON exposure. Furthermore, we demonstrate that LCA restored the DON-induced cell apoptosis by reducing the cleaved caspase 3 and cleaved PARP-1 expression. DON-increased cellular cholesterol and bile acid contents were significantly reduced when LCA was co-treated. Further transcriptomic analysis revealed that the aberrant cholesterol homeostasis genes profile was observed in the cells exposed to DON or pretreated with LCA. We also validated that the key genes involved in cholesterol biosynthesis and transformation (cholesterol to bile acids) were strongly inhibited by the LCA treatment in the DON-exposed cells. Together, this study demonstrated that LCA ameliorated DON-caused toxic apoptosis in IPI-2I cells by maintaining cholesterol metabolism. We suggest that as an endogenous metabolite, LCA may be used as a therapeutic and/or integrated into a dietary intervention against mycotoxin toxicity.
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Research on obesity and related diseases has received attention from government policymakers; interventions targeting nutrient intake, dietary patterns, and physical activity are deployed globally. An urgent issue now is how can we improve the efficiency of obesity research or obesity interventions. Currently, machine learning (ML) methods have been widely applied in obesity-related studies to detect obesity disease biomarkers or discover intervention strategies to optimize weight loss results. In addition, an open source of these algorithms is necessary to check the reproducibility of the research results. Furthermore, appropriate applications of these algorithms could greatly improve the efficiency of similar studies by other researchers. Here, we proposed a mini-review of several open-source ML algorithms, platforms, or related databases that are of particular interest or can be applied in the field of obesity research. We focus our topic on nutrition, environment and social factor, genetics or genomics, and microbiome-adopting ML algorithms.
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BACKGROUND: Hepatitis C virus (HCV) causes a large number of infections worldwide. New infections seem to be increasing according to a report of the World Health Organization in 2015. Although direct-acting antivirals are quite effective for most genotypes of the HCV, some genotypes fail to respond. Therefore, the trend of genotype distribution is vital to better control the development of this infection. AIM: To analyze the distribution and trends of the HCV genotype before and after the emergence of direct-acting antivirals in China. METHODS: We searched all literature published in five electronic databases-China National Knowledge Infrastructure, Wan Fang Data, VIP Chinese Journal Database, Chinese Biomedical Literature Service System, and PubMed-from January 1, 2010 to December 31, 2020. The search strategy combined medical subject headings and free-text terms, including "hepatitis C virus" or "HCV" and "genotype" or "subtype" and "China" or "Chinese". Additional relevant articles were searched by manual selection. Data were extracted to build a database. All of the data were totaled according to regions, periods, routes of transmission, and sexes. The percentages in various stratifications were calculated. RESULTS: There were 76110 samples from 30 provinces included in the study. Genotype 1 (G1) accounted for 58.2% of cases nationwide, followed by G2, G6, G3b, G3a, unclassified and mixed infections (17.5%, 7.8%, 6.4%, 4.9%, 1.8%, and 1.2%, respectively). The constitution of genotype varied among different regions, with G6 and G3b being more common in the south and southwest, respectively (28.1%, 15.4%). The past ten years have witnessed a decrease in G1 and G2 and an increase in G3 and G6 in almost all regions. The drug-use population had the most abundant genotypes, with G6 ranking first (33.3%), followed by G1 and G3b (23.4%, 18.5%). CONCLUSION: G3 and G6 pose a new challenge for HCV infection. This study revealed the distribution of HCV genotypes in China over the past 10 years, providing information for HCV management strategies.
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Clinical cases and animal experiments show that high-fat (HF) diet is involved in inflammatory bowel disease (IBD), but the specific mechanism is not fully clear. A close association between long-term HF-induced obesity and IBD has been well-documented. However, there has been limited evaluation of the impact of short-term HF feeding on the risk of intestinal inflammation, particularly on the risk of disrupted metabolic homeostasis. In this study, we analyzed the metabolic profile and tested the vulnerability of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis after short-term HF feeding in mice. The results showed that compared with the control diet (CD), the fatty acid (FA), amino acid (AA), and bile acid (BA) metabolisms of mice in the HF group were significantly changed. HF-fed mice showed an increase in the content of saturated and unsaturated FAs and a decrease in the content of tryptophan (Trp). Furthermore, the disturbed spatial distribution of taurocholic acid (TCA) in the ileum and colon was identified in the HF group using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). After HF priming, mice on TNBS induction were subjected to more severe colonic ulceration and histological damage compared with their CD counterparts. In addition, TNBS enema induced higher gene expressions of mucosal pro-inflammatory cytokines under HF priming conditions. Overall, our results show that HF may promote colitis by disturbing lipid, AA, and BA metabolic homeostasis and inflammatory gene expressions.
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Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.
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Changes in overall bile acid (BA) levels and specific BA metabolites are involved in metabolic diseases, gastrointestinal, and liver cancer. BAs have become established as important signaling molecules that enable fine-tuned inter-tissue communication within the enterohepatic circulation. The liver, BAs site of production, displayed physiological and functional zonal differences in the periportal zone versus the centrilobular zone. In addition, BA metabolism shows regional differences in the intestinal tract. However, there is no available method to detect the spatial distribution and molecular profiling of BAs within the enterohepatic circulation. Herein, we demonstrated the application in mass spectrometry imaging (MSI) with a high spatial resolution (3 µm) plus mass accuracy matrix-assisted laser desorption ionization (MALDI) to imaging BAs and N-1-naphthylphthalamic acid (NPA). Our results could clearly determine the zonation patterns and regional difference characteristics of BAs on mouse liver, ileum, and colon tissue sections, and the relative content of BAs based on NPA could also be ascertained. In conclusion, our method promoted the accessibility of spatial localization and quantitative study of BAs on gastrointestinal tissue sections and demonstrated that MALDI-MSI was a valuable tool to investigate and locate several BA molecules in different tissue types leading to a better understanding of the role of BAs behind the gastrointestinal diseases.