Evaluating the efficacy of immunotherapy in gastric cancer:Insights from immune checkpoint inhibitors

The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influenced by various factors.This manuscript identified sarcopenia and myosteatosis as independent prognostic factors impacting the outcomes of GC patients treated with ICIs.Additionally,this study introduced a visual predictive model to estimate the prognosis of GC patients.If confirmed by further studies,this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.

Chinese medicine formulas for nonalcoholic fatty liver disease: Overview of systematic reviews

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)affects more than one-quarter of the global population.Due to the lack of approved chemical agents,many patients seek treatment from traditional Chinese medicine(TCM)formulas.A variety of systematic reviews have been published regarding the effectiveness and safety of TCM formulas for NAFLD.AIM To critically appraise available systematic reviews and sort out the high-quality evidence on TCM formulas for the management of NAFLD.METHODS Seven databases were systematically searched from their inception to 28 February 2020.The search terms included“non-alcoholic fatty liver disease,”“Chinese medicines,”“systematic review,”and their synonyms.Systematic reviews involving TCM formulas alone or in combination with conventional medications were included.The methodological quality and risk of bias of eligible systematic reviews were evaluated by using A Measure Tool to Assess Systematic Reviews 2(AMSTAR 2)and Risk of Bias in Systematic Review(ROBIS).The quality of outcomes was assessed by the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system.RESULTS Seven systematic reviews were ultimately included.All systematic reviews were conducted based on randomized controlled trials and published in the last decade.According to the AMSTAR 2 tool,one systematic review was judged as having a moderate confidence level,whereas the other studies were rated as having a low or extremely low level of confidence.The ROBIS tool showed that the included systematic reviews all had a high risk of bias due to insufficient consideration of identified concerns.According to the GRADE system,only two outcomes were determined as high quality;namely,TCM formulas with the HuoXueHuaYu principle were better than conventional medications in ultrasound improvement,and TCM formulas were superior to antioxidants in alanine aminotransferase normalization.Other outcomes were downgraded to lower levels,mainly because of heterogeneity among studies,not meeting optimal information sample size,and inclusion of excessive numbers of small sample studies.Nevertheless,the evidence quality of extracted outcomes should be further downgraded when applying to clinical practice due to indirectness.CONCLUSION The quality of available systematic reviews was not satisfactory.Researchers should avoid repeatedly conducting systematic reviews in this area and focus on designing rigorous randomized controlled trials to support TCM formula applications.

Management of non-alcoholic fatty liver disease patients with sleep apnea syndrome

Nonalcoholic fatty liver disease(NAFLD)is strongly associated with sleep apnea syndrome(SAS).Many NAFLD patients have SAS,and obstructive sleep apnea hypopnea syndrome is also considered to be an independent risk factor for NAFLD,as it contributes to the progression of NAFLD via oxidative stress,lipid peroxidation,inflammation,and insulin resistance.This review aims to provide some recommendations for the management of NAFLD patients with SAS,including diet,exercise,weight loss,and continuous positive airway pressure.This review also highlights the importance of effective strategies in NAFLD prevention and treatment.

Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types

BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide,with the fourth highest mortality among all cancers.Reportedly,in addition to adenomas,serrated polyps,which account for 15%-30%of CRCs,can also develop into CRCs through the serrated pathway.Sessile serrated adenomas/polyps(SSAs/Ps),a type of serrated polyps,are easily misdiagnosed during endoscopy.AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types.METHODS From January 2021 to December 2021,patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital,affiliated with Shanghai University of Traditional Chinese Medicine.Thirty cases each of large intestine damp-heat(Da-Chang-Shi-Re,DCSR)syndrome and spleen-stomach weakness(Pi-Wei-Xu-Ruo)syndrome were reported.Baseline comparison of the general data,typical tongue coating,colonoscopy findings,and hematoxylin and eosin findings was performed in each group.The expression of the Wnt pathway-related proteins,namelyβ-catenin,adenomatous polyposis coli,and mutated in colorectal cancer,were analyzed using immunohistochemistry.RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types(P=0.001).The other aspects did not differ between the two groups.The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups,which was manifested asβ-catenin protein translocation into the nucleus.However,SSAs/Ps patients with DCSR syndrome had more nucleation,higherβ-catenin expression,and negative regulatory factor(adenomatous polyposis coli and mutated in colorectal cancer)expression(P<0.0001)than SSA/P patients with Pi-Wei-Xu-Ruo syndrome.In addition,the SSA/P size was linearly correlated with the related protein expression.CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis.A high-quality colonoscopic diagnosis was essential.The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.

Systems pharmacology approach reveals protective mechanisms of Jian-Pi Qing-Chang decoction on ulcerative colitis

BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.

Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis

AIM To investigate the protective effects of Ampelopsis grossedentata(AMP) on dextran sulfate sodium(DSS)-induced colitis in mice based on systems pharmacology approach.METHODS Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis(UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSSinduced colitis model in C57 BL/6 mice(n = 10/group) was constructed and treated with 5-aminosalicylic acid(100 mg/kg/d) and AMP(400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry.RESULTS The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8.CONCLUSION AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways.

Role of epigenetics in transformation of inflammation into colorectal cancer

Molecular mechanisms associated with inflammation-promoted tumorigenesis have become an important topic in cancer research. Various abnormal epigenetic changes, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, occur during the transformation of chronic inflammation into colorectal cancer(CRC). These changes not only accelerate transformation but also lead to cancer progression and metastasis by activating carcinogenic signaling pathways. The NF-κB and STAT3 signaling pathways play a particularly important role in the transformation of inflammation into CRC, and both are critical to cellular signal transduction and constantly activated in cancer by various abnormal changes including epigenetics. The NF-κB and STAT3 signals contribute to the microenvironment for tumorigenesis through secretion of a large number of pro-inflammatory cytokines and their crosstalk in the nucleus makes it even more difficult to treat CRC. Compared with gene mutation that is irreversible, epigenetic inheritance is reversible or can be altered by the intervention. Therefore, understanding the role of epigenetic inheritance in the inflammation-cancer transformation may elucidate the pathogenesis of CRC and promote the development of innovative drugs targeting transformation to prevent and treat this malignancy. This review summarizes the literature on the roles of epigenetic mechanisms in the occurrence and development of inflammation-induced CRC. Exploring the role of epigenetics in the transformation of inflammation into CRC may help stimulate futures studies on the role of molecular therapy in CRC.

Gut microbiota contributes to the distinction between two traditional Chinese medicine syndromes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.

Recent insights into farnesoid X receptor in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is the hepatic manifestation of metabolic syndrome and is one of the most prevalent liver disorders worldwide. NAFLD can gradually progress to liver inflammation, fibrosis, cirrhosis and even hepatocellular carcinoma. However, the pathogenesis of NAFLD is complex, and no efficient pharmaceutic treatments have yet been established for NAFLD. Accumulating data have shown that the farnesoid X receptor(FXR) plays important roles not only in bile acid metabolism, but also in lipid and carbohydrate homeostasis, inflammatory responses, among others. In this review, we aim to highlight the role of FXR in the pathogenesis and treatment of NAFLD.

Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells

Ulcerative colitis(UC)is a chronic relapsed intestinal disease with an increasing incidence around the world.The pathophysiology of UC remains unclear.However,the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research hotspot.Vasoactive intestinal peptide(VIP)is a kind of endogenous neuropeptide with regulatory activity on intestinal immunity.It has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune system.Regulatory B cells(Bregs)are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune circles.Bregs can regulate immune tolerance by producing interleukin(IL)-10,IL-35,and transforming growth factor-β,suppressing autoimmune diseases or excessive inflammatory responses.The secretion of IL-10 by Bregs induces the development of T helper(Th)0 and Th2 cells.It also induces Th2 cytokines and inhibits Th1 cytokines,thereby inhibiting Th1 cells and the Th1/Th2 balance.With further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients,we believe that Bregs can provide a novel strategy for the clinical treatment of UC.Thus,we aim to review the current literature on this evolving topic.

Progress on haptoglobin and metabolic diseases

Haptoglobin(Hp)is an acidic glycoprotein,existing in the serum and other body fluids of human beings and a variety of mammals.Hp is produced in the liver,white adipose tissue,and the kidney.The genetic polymorphisms and different phenotypes of Hp have different biological functions.Hp has antibacterial,antioxidant,and angiogenic effects and is associated with multiple diseases including simple obesity,vascular complications of diabetes mellitus,nonalcoholic fatty liver disease,hypertension,blood diseases,autoimmune diseases,and malignant tumors.Hp also participates in many life activities,indicating the importance of Hp in further studies.Previously,we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials.However,the specific mechanism of Hp in patients with simple obesity is still unclear.The purpose of this article is to introduce recent research progress on Hp,emphasizing the relationship between Hp and the development of metabolic disease,which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.

Animal models of cathartic colon

The incidence of cathartic colon has been increasing,but satisfactory treatments are still lacking.In order to study the pathological mechanisms of the disorder and identify effective treatment methods,researchers have established different animal models of cathartic colon.This minireview briefly summarizes several common cathartic colon animal models,induced with anthraquinone laxatives such as rhubarb,total anthraquinone,rhein,and emodin,or induced with diphenylmethane laxatives such as phenolphthalein.The advantages and limitations of these models are evaluated and analyzed.We hope that this review will facilitate the selection of suitable models and improve relevant modeling methods.We anticipate the development of more convenient and stable models that can reflect the characteristics of cathartic colon in humans,and serve as useful tools for further studies.

Jianpi Qingchang Bushen decoction improves inflammatory response and metabolic bone disorder in inflammatory bowel disease-induced bone loss

BACKGROUND Bone loss and osteoporosis are commonly described as extra-intestinal manifestations of inflammatory bowel disease(IBD).Jianpi Qingchang Bushen decoction(JQBD)is a prescription used in clinical practice.However,further studies are needed to determine whether JQBD regulates the receptor activator of nuclear factor kappa B(NF-κB)(RANK)/receptor activator of NF-κB ligand(RANKL)/osteoprotegerin(OPG)pathways and could play a role in treating IBD-induced bone loss.AIM To evaluate the therapeutic effect of JQBD in IBD-induced bone loss and explore the underlying mechanisms.METHODS An IBD-induced bone loss model was constructed by feeding 126-to-8-wk-old interleukin-10(IL-10)-knockout mice with piroxicam for 10 d.The mice were randomly divided into model and JQBD groups.We used wild-type mice as a control.The JQBD group was administered the JQBD suspension for 2 wk by gavage,while the control and model groups were given normal saline at the corresponding time points.All mice were killed after the intervention.The effect of JQBD on body weight,disease activity index(DAI),and colon length was analyzed.Histopathological examination,colon ultrastructure observation,and micro-computed tomographic scanning of the lumbar vertebrae were performed.The gene expression of NF-κB,tumor necrosis factor-α(TNF-α),IL-1β,IL-6,and IL-8 in the colon was evaluated by real-time polymerase chain reaction.Colon samples were assessed by Western blot for the expression of RANKL,OPG,RANK,and NF-κB proteins.RESULTS The model group lost body weight,had a shorter colon,and showed a dramatic increase in DAI score,whereas JQBD had protective and therapeutic effects.Treatment with JQBD significantly improved inflammatory cell infiltration and reduced crypt abscess and ulcer formation.Threedimensional imaging of the vertebral centrum in the model group revealed a lower bone mass,loose trabeculae,and“rod-shaped”changes in the structure compared to the control group and JQBD groups.The bone volume/total volume ratio and bone mineral density were significantly lower in the model group than in the control group.JQBD intervention downregulated the NF-κB,TNF-α,IL-1β,IL-6,and IL-8 m RNA expression levels.The RANKL and OPG protein levels were also improved.CONCLUSION JQBD reduces inflammation of the colonic mucosa and inhibits activation of the RANK/RANKL/OPG signaling pathway,thereby reducing osteoclast activation and bone resorption and improving bone metabolism.

Vitamin E Therapy in Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is closely related to oxidative stress. Vitamin E (VE) is an effective antioxidant, which could relieve NAFLD symptoms by improving the balance of oxidation and anti-oxidation. However, recent researches indicate that the functional mechanisms of VE are not only limited to anti-oxidation, but also include adjusting the metabolism disorders of glucose and lipid. Furthermore, the efficacy of VE remains controversial in the treatment of NAFLD by far, and the suitable condition of patient, drug dosage, drug safety and course of treatment during clinical application still need to be discussed. Therefore, this paper reviewed the recent study progresses of clinical application of VE alone and VE and other drugs.

RNA-Seq profiling of circular RNAs in human colorectal cancer 5-fluorouracil resistance and potential biomarkers

BACKGROUND Colorectal cancer(CRC)is a commonly diagnosed cancer of the digestive system worldwide.Although chemotherapeutic agents and targeted therapeutic drugs are currently available for CRC treatment,drug resistance is a problem that cannot be ignored and needs to be solved.AIM To explore the relationship between circular RNA(circRNA)and CRC drug resistance.circRNA plays a key role in the occurrence and development of cancers,but its function in the process of drug resistance has not been widely revealed.METHODS To explore the role of circRNA in 5-fluorouracil(5-Fu)resistance,we performed the circRNA expression profile in two CRC cell lines and their homologous 5-Fu resistant cells by high-throughput sequencing.RESULTS We validated the differentially expressed circRNAs in other two paired CRC cells,confirmed that circ_0002813 and circ_0000236 could have a potential competitive endogenous RNA mechanism and be involved in the formation of 5-Fu resistance.And we combined the sequencing results of mRNA to construct the regulatory network of circRNA-miRNA-mRNA.CONCLUSION Our study revealed that circ_0002813 and circ_0000236 may as the biomarkers to predict the occurrence of 5-Fu resistance in CRC.

Macrophages play a role in inflammatory transformation of colorectal cancer

Colorectal cancer(CRC)is one of the most common and fatal cancers worldwide,and it is also a typical inflammatory cancer.The function of macrophages is very important in the tissue immune microenvironment during inflammatory and carcinogenic transformation.Here,we evaluated the function and mechanism of macrophages in intestinal physiology and in different pathological stages.Furthermore,the role of macrophages in the immune microenvironment of CRC and the influence of the intestinal population and hypoxic environment on macrophage function are summarized.In addition,in the era of tumor immunotherapy,CRC currently has a limited response rate to immune checkpoint inhibitors,and we summarize potential therapeutic strategies for targeting tumorassociated macrophages.

Jianpi Qingchang Decoction-containing serum regulates the autophagy ofinterstitial cells

Objective： To investigate the effects of Jianpi Qingchang Decoction-containing serum （JQD-CS） on interstitial cells ofCajal （ICCs） autophagy and cell cycle arrest in vitro. Methods： ICCs were collected from the small intestines of miceand analyzed using an anti-c-Kit antibody. ICCs were divided into five groups： the blank group, the rapamycin group （anautophagy inducer）, the 5% （rapamycin ＋ 5% JQD-CS）, the 20% （rapamycin ＋ 20% JQD-CS） JQD-CS groups, and the3-Methyladenine （3-MA） group （rapamycin ＋ 3-MA; positive control）. Transmission electron microscopy was used toobserve the ultrastructure of ICCs. Western blotting was used to detect the expression of microtubule-associated protein1 light chain 3 （LC3-II）, Beclin-1, phosphatidylinositol 3-kinase （PI3K）, p-PI3K, protein kinase B （AKt）, p-AKt,mammalian target of rapamycin （mTOR）, and p-mTOR. Ca2＋ current was examined by patch-clamp experiments. Cellcycle was detected by flow cytometry. Results： Unlike in the rapamycin group, the ICC structures were more integratedand a lower number of autophagic vacuoles were observed in the 20% JQD-CS group. Moreover, the expression ofLC3-II and Beclin-1 decreased, the expression of c-Kit, p-PI3K, p-AKt increased, the maximum current density valuedecreased, and the number of cells in the G1 phase increased while those in the G2/M phase decreased, with the additionof 20% JQD-CS. Conclusion： JQD-CS can antagonize rapamycin-induced autophagy in ICCs in vitro by promoting thephosphorylation of PI3K/AKt pathway, inhibiting Ca2 ＋ inflow, and regulating the cell cycle.

Single-cell RNA-sequencing combined with bulk RNA-sequencing analysis of peripheral blood reveals the characteristics and key immune cell genes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response.Single-cell RNA sequencing(scRNA-seq)can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine,analyze the characteristics of cells with the same phenotype,and provide new insights into the growth and development of intestinal organs,the clonal evolution of cells,and immune cell changes.These findings can provide new ideas for the diagnosis and treatment of intestinal diseases.To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC.METHODS Using the Gene Expression Omnibus(GEO)database,we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing(RNA-seq)to reveal the core genes of UC.We then combined weighted gene correlation network analysis(WGCNA)and least absolute shrinkage and selection operator(LASSO)analysis to reveal diagnostic markers of UC.RESULTS After processing the scRNA-seq data,we obtained data from approximately 24340 cells and identified 17 cell types.Through intercellular communication analysis,we selected monocyte marker genes as the candidate gene set for the prediction model.Construction of a WGCNA coexpression network identified RhoB,cathepsin D(CTSD)and zyxin(ZYX)as core genes.Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells.Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses,which are associated with many challenges in the diagnosis and treatment of UC.CONCLUSION Through scRNA-seq analysis,LASSO diagnostic model building and WGCNA,we identified RhoB,CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.

DNA methylation of SMPD3-based diagnostic biomarkers of NASH and mild fibrosis

Non-alcoholic fatty liver disease(NAFLD)is a liver condition that is widely prevalent across the world.A considerable number of people with NAFLD have the potential to progress to a more severe form of the condition known as nonalcoholic steatohepatitis(NASH),accompanied by bridging fibrosis.This advancement is more likely if the patient has metabolic risk factors such as obesity or type 2 diabetes that deteriorate over time.Additionally,even slight inflammation or fibrosis in NAFLD can significantly increase the likelihood of progression compared to steatosis alone.This underscores the importance of revising the present methods of monitoring NAFLD patients to ensure early detection and effective management of the disease.