Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

ObjectiveTo analyze the incidence and trend of stroke in Beilun District, so as to provide evidence for identifying influencing factors and reducing stroke incidence. MethodsStroke cases from 2012 to 2023 were extracted from the Ningbo Chronic Disease Collaborative Management System. Population information of Beilun District during the same period was also collected. The annual incidence and trends of stroke were analyzed. ResultsFrom 2012 to 2023, the age-standardized incidence rate of stroke in Beilun District, Ningbo City was 317.68/100 000, showing an increasing trend with an average annual percentage change (AAPC) of 2.267% (P=0.034). Among all subdistricts in Beilun District, two showed a downward trend in incidence, while the rest showed an upward trend. The crude incidence rate of stroke was significantly higher in males than that in females (P<0.001). The age-standardized incidence rate in males was 406.08/100 000, showing an increasing trend (AAPC=3.956%, P<0.001). The incidence of stroke also showed an increasing trend in the following age groups: 30‒<45 years (AAPC=6.340%, P=0.004), 45‒<60 years (AAPC=4.997%, P<0.001), and 60‒<75 years (AAPC=3.282%, P=0.042). Across all years, males had higher crude incidence rates in both ischemic and hemorrhagic stroke than females (P<0.05). The age-standardized incidence rate of ischemic stroke showed a rising trend in both males and the general population (male AAPC=4.905%, P<0.001; overall population AAPC=3.065%, P=0.001). ConclusionThe age-standardized incidence of stroke in Beilun District is on the rise, with higher crude incidence rate in males than that in females. The onset age of stroke is gradually declining. The age-standardized incidence rate of male ischemic stroke shows a clear upward trend.

Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation(FMT)on chemotherapy-induced diarrhea(CID)in mice.Methods Fifteen C57BL/6N mice were divided into control group,CID model group and CID+FMT group according to the random number distribution and remainder grouping method,with 5 mice per group.Control group received no intervention,and their feces were used to prepare fecal bacteria suspension.CID model group was injected intraperitoneally with fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,followed by gavage with 0.1 ml of saline on alternate days.CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week,followed by intraperitoneal injection of fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,with the experiment ending on the 14th day.During the experiment,the mice's food intake and body weight were recorded.At the end of the experiment,the mice were euthanized with deep carbon dioxide anesthesia,and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin(HE)staining and histopathological examination.Fecal samples were collected for 16S rRNA gene sequencing.Shannon index,Simpson index and Chao1 algorithm were used to analyze the α-diversity species of the intestinal flora in each group of mice.Similarity analysis(Anosim)was used to perform non-parametric on the inter-group differences of intestinal flora among the mice.Linear discriminate analysis size effect(LEfSe)and nonmetric multidimensional scaling(NMDS)were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice.Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group(P<0.05),while there was no significant difference between CID+FMT group and CID model group(P>0.05).The weight of mice in CID model group decreased by 42.04%,while control group mice gained 10.24%,with a significant difference between the two groups(P<0.05).The weight of mice in CID+FMT group decreased by 8.12%,which was significantly improved compared to CID model group(P<0.05).HE staining results revealed the intestinal mucosal structure in CID model group was severely damaged,with atrophy and deformation,accompanied by inflammatory cell infiltration,and the pathological score was higher than that of control group(P<0.05).Compared with CID model group,the intestinal mucosal integrity and crypt cells in the CID+FMT group were improved,with less damage,and the pathological score was lower than that of CID model group,but the difference was not statistically significant(P>0.05).The α-diversity analysis showed that there were significant differences in the Shannon,Simpson and Chao1 indices among the three groups(P<0.05).ANOSIM and NMDS analysis revealed that the intestinal flora in CID+FMT group was closer to the normal intestinal flora compared to CID model group.LEfSe analysis showed that the intestinal flora in CID model group was enriched in famliy_Bacteroidaceae,and the intestinal flora in CID+FMT group was similar to that of control group,with an enrichenment of familiy_Enterobacteriaceae.Conclusion Homogeneous FMT can improve the abundance of intestinal flora in CID mice,making it more similar to normal intestinal flora,thereby protecting intestinal mucosa,reducing damage and alleviating the severity of CID.

Good endometrial receptivity is an essential factor for embryo implantation,and gene expression in endometrial tissue during the window of implantation(WOI)is closely related to receptivity.Transcriptome sequencing technology enables the identification of gene expression profiles of endometrium during different menstrual phases,as well as microRNAs and long-chain non-coding RNA sequences involved in regulating gene expression.Combining this technology with bioinformatics analysis provides a better understanding of specific gene expression during the receptive period and offers technical support for studying its regulatory mechanism.Moreover,gene expression profiles of the endometrium during different menstrual phases hold significant clinical application value for accurately assessing endometrium receptivity in infertility patients and those with repeated implantation failure,thereby guiding individualized embryo transfer strategies.This review summarizes the progress of transcriptome sequencing in evaluating human endometrial receptivity and discusses future research directions.This review aims to understand the complex molecular mechanisms of endometrial receptivity formation and regulation from the transcriptional level,in order to improve the implantation rate of embryos in assisted reproductive technology and reduce the abortion rate.

Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans ; tau Proteins/physiology* ; Phosphorylation ; Hypoxia-Ischemia, Brain/physiopathology* ; Animals ; Oxidative Stress

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans