Promise and challenges of traditional Chinese medicine,specifically Calculus bovis,in liver cancer treatment

Liver cancer,one of the most common malignancies worldwide,ranks sixth in incidence and third in mortality.Liver cancer treatment options are diverse,inclu-ding surgical resection,liver transplantation,percutaneous ablation,transarterial chemoembolization,radiotherapy,chemotherapy,targeted therapy,immuno-therapy,and traditional Chinese medicine(TCM).A multidisciplinary team(MDT)is essential to customize treatment plans based on tumor staging,liver function,and performance status(PS),ensuring individualized patient care.Treatment decisions require a MDT to tailor strategies based on tumor staging,liver function,and PS,ensuring personalized care.The approval of new first-line and second-line drugs and the establishment of standard treatments based on immune checkpoint inhibitors have significantly expanded treatment options for advanced liver cancer,improving overall prognosis.However,many patients do not respond effectively to these treatments and ultimately succumb to the disease.Modern oncology treatments,while extending patient survival,often come with severe side effects,resistance,and damage to the body,negatively impacting quality of life.Huang et al's study published at World Journal of Gastroenterology rigorously validates the anticancer properties of Calculus bovis,enhancing our understanding of TCM and contributing to new liver cancer treatment strategies.For over 5000 years,TCM has been used in East Asian countries like China to treat various diseases,including liver conditions.Analysis of real-world clinical data suggests that for patients with advanced-stage tumors lacking effective treatments,integrated TCM therapies could provide significant breakthroughs.

Heterogeneity of Outcomes Reporting in Trials Evaluating Traditional Chinese Medicine Breast Massage for Stasis Acute Mastitis: A Methodological Review

Objective To systematically analyze the current status of outcomes reporting in clinical trials on treating stasis acute mastitis with Traditional Chinese Medicine breast massage.Methods We searched CNKI,Wanfang,VIP,Sino Med,Pub Med,Web of Science,Embase,Cochrane library,JBI,CINAHL,Psyc INFO,Clinical Trials Registry Platform portal,Clinical Trials Registry,Australian New Zealand Clinical Trials Registry,Center Watch Registry from inception to May 15,2022 to find randomized controlled trials,non-randomized controlled trials,case series and cohort studies which reported the outcomes of stasis acute mastitis managed with Traditional Chinese Medicine breast massage,with search terms of mastitis,acute mastitis,lactation mastitis,puerperal mastitis,breast problem,breast engorgement,milk stasis,blocked ducked,breast pain,breast massage,and acupoint massage.Outcomes and the measurement schemes(measurement methods,timing of assessing outcome,frequency of assessing outcome,measurers)were extracted from the included studies.We used the Management of Otitis Media with Effusion in Children with Cleft Palate(MOMENT)to assess the quality of each study,then categorized outcomes derived from the included studies into different domains according to the Outcome Measures in Rheumatology Arthritis Clinic Trials(OMERACT)Filter 2.1 framework.Results We identified 85 clinical trials,in which 54 different outcomes were reported.A total of 81.2%(69/85)of studies were assessed as medium quality with a mean score of 2.6,and 18.8%(16/85)as low quality with a mean score of 0.9.These outcomes were organized in three core areas.Lump size(89.4%,76/85)was the most frequently reported outcome,followed by breast pain(69.4%,59/85)and milk excretion(68.2%,58/85).Five methods were used to assess lump size and four methods to assess breast pain.Conclusions The outcomes reported in clinical trials regarding stasis acute mastitis treated by Traditional Chinese Medicine breast massage are heterogeneous.Developing a core outcome set to achieve consistent standards for reporting outcomes and modalities for validation of the outcomes is clearly warranted.

Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer

BACKGROUND The current prognostic significance of perigastric tumor deposits(TDs)in gastric cancer(GC)remains unclear.AIM To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC.METHODS This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1,2012 to December 31,2017 at the Chinese PLA General Hospital.According to the presence of perigastric TDs or not,the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching.The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling.The Kaplan-Meier method was used to plot survival curves.Multivariate Cox regression modeling and the log-rank test were used to analyze the data.RESULTS Perigastric TDs were found to be positive in 339(5.09%)of the 6672 patients with GC,among whom 237 were men(69.91%)and 102 were women(30.09%)(2.32:1).The median age was 59 years(range,27 to 78 years).Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients(P<0.05).The 1-,3-,and 5-year overall survival rates of GC patients with TDs were 68.3%,19.6%,and 11.2%,respectively,and these were significantly poorer than those without TDs of the same stages.There was significant variation in survival according to TD locations among the GC patients(P<0.05).A new TNM staging framework for GC was formulated according to TD location.When TDs appear in the gastric body,the original stages T1,T2,and T3 are classified as T4a with the new framework,and the original stages T4a and T4b both are classified as T4b.When TDs appear in the lesser curvature,the previous stages N0,N1,N2,and N3 now both are classified as N3.When TDs appear in the greater curvature or the distant tissue,the patient should be categorized as having M1.With the new GC staging scheme including TDs,the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs.CONCLUSION TDs are a poor prognostic factor for patients with primary GC.The location of TDs is associated with the prognosis of patients with primary GC.Accordingly,we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.

Current status of treatments of pancreatic and peripancreatic collections of acute pancreatitis

Pancreatic and peripancreatic collections are the main local complications of acute pancreatitis with a high incidence.In the early phase,most acute pancreatic and peripancreatic collections can resolve spontaneously with supportive treatment.However,in some cases,they will develop into pancreatic pseudocyst(PPC)or walled-off necrosis(WON).When causing symptoms or coinfection,both PPC and WON may require invasive intervention.Compared to PPC,which can be effectively treated by endoscopic ultrasound-guided transmural drainage with plastic stents,the treatment of WON is more complicated and challenging,particularly in the presence of infected necrosis.In the past few decades,with the development of minimally invasive interventional technology especially the progression of endoscopic techniques,the standard treatments of those severe complications have undergone tremendous changes.Currently,based on the robust evidence from randomized controlled trials,the step-up minimally invasive approaches have become the standard treatments for WON.However,the pancreatic fistulae during the surgical step-up treatment and the stent-related complications during the endoscopic step-up treatment should not be neglected.In this review article,we will mainly discuss the indications of PPC and WON,the timing for intervention,and minimally invasive treatment,especially endoscopic treatment.We also introduced our preliminary experience in endoscopic gastric fenestration,which may be a promising innovative method for the treatment of WON.

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis

Background:In sepsis,vitamin D binding protein(VDBP)has been shown to be low-expressed.The current study examined the relationship between serum VDBP level and liver injury in sepsis patients,as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide(LPS).Methods:The human study included 78 sepsis patients and 50 healthy volunteers.Sepsis patients were categorized into sepsis survivor group(n=43)and sepsis non-survivor group(n=35)based on 28-day mortality for data analysis.Adult male C57BL/6 mice were subjected to cecal ligation and puncture(CLP).Serum samples were collected on day 1,3,5 and 7 to determine the levels of VDBP,25-hydroxyvitamin D[25(OH)D_(3)],1,25-dihydroxyvitamin D[1,25(OH)_(2)D_(3)],interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α).Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.Results:Serum levels of VDBP,25(OH)D_(3),and 1,25(OH)_(2)D_(3)were significantly lower in sepsis patients vs.the healthy control(P<0.001),as well as in the sepsis non-survivor group vs.the sepsis survivor group(P<0.001,P=0.0338,or P=0.0013,respectively).Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation(APACHE)II score(r=−0.2565,P=0.0234)and Sequential Organ Failure Assessment score(r=−0.3522,P=0.0016),but lower serum albumin(ALB,r=0.4628,P<0.001)and total protein(TP,r=0.263,P=0.02).In CLP mice,there was a 5-day period of serum VDBP reduction,followed by return towards the baseline on day 7.VDBP was also decreased in LPS-treated THLE2 cells(P<0.001).VDBP overexpression reduced LPS-induced THLE2 damage.Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.Conclusion:VDBP may be protective against sepsis-induced liver injury.

Leukocyte immunoglobulin‐like receptor B4:A keystone in immune modulation and therapeutic target in cancer and beyond

Leukocyte immunoglobulin‐like receptor B4(LILRB4)significantly impacts immune regulation and the pathogenesis and progression of various cancers.This review discusses LILRB4's structural attributes,expression patterns in immune cells,and molecular mechanisms in modulating immune responses.We describe the influence of LILRB4 on T cells,dendritic cells,NK cells,and macrophages,and its dual role in stimulating and suppressing immune activities.The review discusses the current research on LILRB4's involvement in acute myeloid leukemia,chronic lymphocytic leukemia,and solid tumors,such as colorectal cancer,pancreatic cancer,non‐small cell lung cancer,hepatocellular carcinoma,and extramedullary multiple myeloma.The review also describes LILRB4's role in autoimmune disorders,infectious diseases,and other conditions.We evaluate the recent advancements in targeting LILRB4 using monoclonal antibodies and peptide inhibitors and their therapeutic potential in cancer treatment.Together,these studies underscore the need for further research on LILRB4's interactions in the tumor microenvironment and highlight its importance as a therapeutic target in oncology and for future clinical innovations.

Long-Term Outcome of Dynesys Dynamic Stabilization for Lumbar Spinal Stenosis

Background： Many clinical studies over the past decade have indicated positive outcomes for patients treated with Dynesys dynamic stabilization for lumbar degenerative disease. However, long-term outcomes of Dynesys for lumbar spinal stenosis are rarely reported. The aim of this study was to analyze the long-term clinical and radiologic outcomes for patients with lumbar spinal stenosis treated with Dynesys stabilization. Methods： Thirty-eight patients with lumbar spinal stenosis were treated with Dynesys stabilization from July 2008 to March 2010. The minimal duration of follow-up was 72 months. The patients were divided into stenosis and spondylolisthesis groups according to degenerative spondylolisthesis. Clinical outcomes were evaluated using the Oswestry Disability Index （ODI） and visual analog scale （VAS）. Radiographic evaluations included range of motion （ROM） and the disc heights of stabilized segments and the upper adjacent segments. We also evaluated the occurrence of radiographic and symptomatic adjacent segment degeneration （ASD）. Results： There were 23 patients in stenosis group and 15 patients in spondylolisthesis group. The ODl scores were significantly improved at the final follow-up evaluation, as compared to the baseline values （ 16.1± 5.7 vs. 57.2 ± 14.2, t = 61.4 l, P 〈 0.01 ）. The VA S scores for back and leg pain were significantly improved from 4.82 ±0.89 and 4.04 ± 0.82 preoperatively to 0.93± 0.61 and 0.54 ± 0.51 postoperatively （t = 6.59, P 〈 0.01, and t = 5.91, P 〈 0.01, respectively）. There were no differences between the two groups with respect to VAS and ODI scores. The ROM of stabilized segments decreased significantly from 7.8°± 2.4° to 4.5° ± 1.5° （t = 7.18, P 〈 0.05）, while the upper adjacent segments increased significantly from 8.3° ± 2.4° to 10.4° ± 2.4° （t = 2.87, P = 0.01）. The change in disc height of stabilized segments was not significant （11.9 ±2.1 preoperatively vs. 12.5 ± 1.5 postoperatively, t = 1.43, P = 0.15）, whereas the decrease in disc height of the upper adjacent segments was significant （12.5 ±2.0 preopcratively vs. 11.0 ± 1.7 postoperatively, t = 2.94, P = 0.01 ）. The occurrence of radiographic and symptomatic ASD was 16% （6/38） and 3% （1/38）, respectively. Conclusions： Decompression and Dynesys stabilization for lumbar stenosis with or without spondylolisthesis showed good long-term clinical and radiographic results. Lumbar stenosis with or without Grade I spondylolisthesis, particularly in patients 〈60 years of age with mild-to-moderate lumbar disc degeneration, would be one of the main indications for the Dynesys system.

Effect of Modified Xijiao Dihuang Decoction (加味犀角地黄汤) on Intestinal Flora and Th17/Treg in Rats with Radiation Enteritis

Objective To observe the effect of Modified Xijiao Dihuang Decoction(加味犀角地黄汤,MXDD)on rats with radiation enteritis,and explore its action mechanism.Methods Thirty female Sprague Dawley rats were divided into the control,model,dexamethasone(DXM),golden bifid(GB)and MXDD groups using random number table,6 rats in each group.Except the control group,the other rats were developed into radiation enteritis model by exposing to a single 60Co-γray at a dose of 11 Gy.The rats in the DXM,GB and MXDD groups were treated with DXM(1.425 mg/kg),GB(0.8 g/kg)and MXDD(36.0 g/kg)for 3 days,respectively.Body weight and diarrhea condition of rats were evaluated daily.On day 3,the feces of rats were collected for intestinal flora detection and the small intestinal tissues were also collected.Bacterial species annotation,alpha and beta diversities as well as composition of intestinal flora were detected and compared.The protein and mRNA expressions of interleukin 17(IL-17),retinoid-related orphan nuclear receptor gamma t(ROR-γt)and forkhead/winged helix transcription factor p3(FoxP3)were determined by Western blot and polymerase chain reaction,respectively.The abundance and diversity of intestinal flora as well as the proportion at the phylum and genus levels were assayed by 16S rRNA metagenome sequencing.Correlation between intestinal flora and Th17/Treg was analyzed by heatmap method.Results On day 1 to 3 after radiation,compared with the control group,the body weight in model group was decreased(P<0.05 or P<0.01).Compared with the model group,MXDD could alleviate weight loss and diarrhea caused by irradiation.At the phylum level,MXDD cause a significant increase in Firmicutes,and a decrease in Proteobacteria(P<0.05 or P<0.01).At the genus level,MXDD reduced the proportion of Escherichia Shigella(P<0.01).In addition,IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment(P<0.05).Besides,Firmicutes and Lactobacillus were positively correlated with FoxP3(r=0.73,0.79,respectively;P<0.01),negatively correlated with IL-17(r=0.66,0.64,respectively;P<0.01 or P<0.05)and ROR-γt(r0.73,0.81,respectively;P<0.01).Proteobacteria and Escherichia Shigella both had positive correlation with IL-17(r 0.77,0.57,respectively;P<0.01 or P<0.05)and ROR-γt(r=0.94,0.79,respectively;P<0.01)and negative correlation with FoxP3(r0.74,0.65;P<0.01).Conclusion MXDD could improve the survival status of irradiated rats by regulating the richness,diversity and composition of intestinal flora,and restoring the balance of Th17/Treg.

Factors influencing outcomes of intra-aortic balloon counterpulsation in elderly patients

Background Intra-aortic balloon counterpulsation （IABP） is a mechanical cardiac-assist device that is used for cardiac support. There are no published reports about the use of IABP in elderly Chinese patients, especially for those over 80 years old. The aim of this study was to describe the clinical outcomes, influencing factors, and complications in patients 〉80 years old and requiring IABP. Methods We performed a retrospective study of 134 consecutive patients who received IABP therapy. Based on age, we defined two groups; those 〉80 years old and those 〈80 years old. Results The overall mortality was 41.8%. Patients -〉80 years old had higher mortality rates than those 〈80 years old （47.9% vs. 30.2%）. Patients 〉80 years old had fewer successful revascularizations （45.8%） and more pulmonary infections （47.9%） than patients 〈80 years old （60.3% and 30.2%, respectively）; these differences were statistically significant. The most common non-cardiac complication was pulmonary infection. Cardiogenic shock and pulmonary infection were risk factors for all-cause, in-hospital mortality, whereas revascularization success was a negative risk factor for the -〉80 years old patients. Conclusions IABP may be successfully and safely employed in patients 〉80 years old, having severe heart disease, with few complications. Patients 〉80 years old who need IABP therapy are less likely to have a successful revascularization and are more likely to develop pulmonary infections than patients 〈80 years old.

Effect of optimal combination of Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) on proliferation and apoptosis of A549 lung cancer cells

OBJECTIVE: To investigate the effect of optimal combination(E) of Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) on proliferation and apoptosis of A549 lung cancer cells and the possible mechanism underpinning the action.METHODS: A uniform design method was used to optimize the E of Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) in A549 lung cancer cells. MTS assay was applied to analyze the effect of the component formula ofHuangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) on A549 cells viability in various uniform design groups. A549 cells with exponential growth in routine culture were exposed to Co Cl_2(200 μmol/L) to mimic hypoxic conditions. Group 0 was treated with RPMI-1640, the group Co Cl_2 was treated with Co Cl_2(200 μmol/L),the group DDP + Co Cl_2 was treated with 4 mg/L Cisplatin injection(DDP) + Co Cl_2(200 μmol/L), and the drug group was treated with various dose of E(0.5 E, 1 E, 2 E) + Co Cl_2(200 μmol/L). All groups were cultured for 24 h. Cell apoptosis was measured by Annexin V-FITC/propidium iodide double staining and flow cytometry. Western blot assay and quantitative real-time polymerase chain reaction(q RT-PCR) were employed to detect the protein and m RNA expression of B-celllymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax) and cysteinyl aspartate specific proteinase-3(caspase-3).RESULTS: The E obtained by the uniform design was comprise of 200 mg/L Astragalus polysaccharide(X1) and 32 mg/L Curcumin(X3). Group DDP+Co Cl_2, group 1 E + Co Cl_2 and group 2 E + Co Cl_2 promoted the apoptosis of A549 cells(P < 0.05). Group1 E + Co Cl_2 and group 2 E + Co Cl_2 had no statistically significant differences compared with the group DDP + Co Cl_2(P > 0.05). Compared with group 0, various doses of E + Co Cl_2 could up-regulate the expression of Bax and caspase-3 and down-regulate the expression of Bcl-2 at protein and m RNA levels(P < 0.05).CONCLUSION: Astragalus polysaccharide and Curcumin was the optimal combination of Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Cur-cumae Phaeocaulis). E promoted the apoptosis of A549 cells. Combination of Astragalus polysaccharide and Curcumin increased the expression of Bax and caspase-3, and decreased the expression of Bcl-2 to initiate apoptosis in A549 cells under chemical-induced hypoxia.

Clinical characteristics, treatments, and prognosis of patients with multiple primary carcinoma of head and neck

To the Editor: Multiple primary carcinoma (MPC) or secondary primary carcinoma refers to two or more malignant tumors occurring in the same organ or different organs of a patient. MPC is classified into synchronous MPC (time between diagnoses ≤6 months) and metachronous MPC (time between diagnoses >6 months).[1] Clinically, MPC was easily misdiagnosed as the recurrence and metastasis of malignant tumor. In head and neck MPC patients, the correct diagnosis and active treatments are important.

Biomarkers or factors for predicting the efficacy and adverse effects of immune checkpoint inhibitors in lung cancer: achievements and prospective

Immune checkpoint inhibitors (ICIs) are widely used in lung cancer therapy due to their effectiveness and minimal side effects. However, only a few lung cancer patients benefit from ICI therapy, driving the need to develop alternative biomarkers. Programmed death-ligand 1 (PD-L1) molecules expressed in tumor cells and immune cells play a key role in the immune checkpoint pathway. Therefore, PD-L1 expression is a prognostic biomarker in evaluating the effectiveness of programmed death-1 (PD-1)/PD-L1 inhibitors. Nevertheless, adverse predictive outcomes suggest that other factors are implicated in the response. In this review, we present a detailed introduction of existing biomarkers concerning tumor abnormality and host immunity. PD-L1 expression, tumor mutation burden, neoantigens, specific gene mutations, circulating tumor DNA, human leukocyte antigen class I, tumor microenvironment, peripheral inflammatory cells, and microbiome are discussed in detail. To sum up, this review provides information on the current application and future prospects of ICI biomarkers.

Efficacy of Liangxue Guyuan decoction(凉血固元汤)on radiation-induced intestinal injury in rats via the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-kappa B pathway

OBJECTIVE:To evaluate the efficacy of Liangxue Guyuan decoction(凉血固元汤,LGD)on radiation-induced intestinal injury in rats,and the possible underlying mechanism of action.METHODS:A total of 255 male Sprague-Dawley rats were used.15 rats were assigned to the control group and the remaining 240 rats were exposed to a^(60)Co source at a dose of 11 Gy.Irradiated rats were randomly divided into model,dexamethasone(DXM),low-dose LGD(LGDl),and high-dose LGD(LGDh)groups and treated for 11 d.The survival rate,weight of body,intestinal pathology and the expression of toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),and nuclear`factor-kappa B(NF-κB)were recorded.RESULTS:Radiation reduced the survival rate and weight of rats,destroyed the intestinal structure,induced an inflammatory reaction,and increased both protein and mRNA expression of TLR4,MyD88,and NF-κB in ileum.However,LGDh increased the survival rate,inhibited weight loss,alleviated inflammation and improve the expression of TLR4 pathway.CONCLUSIONS:LGD increased the survival rate and inhibit weight loss of irradiated rats,and reduced inflammation and intestinal injury.The underlying mechanism may involve regulation of the TLR4/MyD88/NF-κB pathway.

Outcomes of super minimally invasive surgery vs.esophagectomy for superficial esophageal squamous cell carcinoma:a single-center study based on propensity score matching

Super minimally invasive surgery(SMIS)is a new concept proposed in 2016,which is defined as“curing the disease while preserving the integrity of human organ anatomy.”[1]Its concept has been accepted by the World Endoscopy Organization and Chinese Society of Digestive Endoscopy.The obvious advantage of SMIS is to cure diseases without damaging the structure and function of organs.For cancer patients,it can ensure a normal survival time and postoperative quality of life(QoL).

Long-term outcomes of peroral endoscopic myotomy with simultaneous submucosal and muscle dissection (POEM-SSMD) for achalasia with severe interlayer adhesions

Many previous studies have confirmed the effectiveness and safety of peroral endoscopic myotomy(POEM)to treat achalasia.However,severe interlayer adhesions preclude the establishment of a submucosal tunnel and then result in aborted POEM procedures.To address this challenge,we introduced POEM with simultaneous submucosal and muscle dissection(POEM-SSMD)in 2014.[1]During the short-term follow-up,the symptoms of the patient were significantly improved.Thus,for patients with esophageal interlayer adhesions,the relative indications of POEM may be extended.Nevertheless,only a few case reports using this technique with a shorter follow-up have been published to date.Hence,the present study aimed to further report the long-term outcomes of POEM-SSMD for achalasia with severe interlayer adhesions in a relatively larger population.

Novel Hemorrhagic Risk Score in Elderly Patients with Coronary Artery Disease and Gastrointestinal Malignant Tumor Comorbidity:A 10-year Clinical Inpatient Data Analysis from 2 Medical Centers

Objective:Older patients with comorbidity,such as coronary heart disease(CHD)and malignant gastrointestinal tumors,are at a high risk of bleeding events.However,risk prediction models based on risk factor assessment remain unclear.This study aimed to establish an individualized bleeding risk assessment system based on the analysis of 10-year inpatient clinical big data.Methods:Total clinical data of 56,819 patients with CHD and 25,988 patients with malignant digestive tract tumors(admitted from January 2008 to December 2017)were retrospectively collected at the First and Second Medical Centers of Chinese People's Liberation Army General Hospital.Among them,1307 patients with CHD and malignant digestive tract tumors were screened as the derivation cohort.The dependent variable was the occurrence of major clinical bleeding events.Baseline statistics and hypothesis tests of differences were performed for independent variables according to the occurrence of bleeding.Decision Tree,eXtreme Gradient Boosting(XGBoost),logistic regression,and random forest models were used for comparison.The accuracy,sensitivity,specificity,and area under the receiver operating characteristic curve(AUC-ROC)were applied as the criteria for evaluating and verifying model performance.To evaluate this developed model,another cohort comprising 454 patients(admitted from January 2018 to December 2019)was prospectively enrolled as the validation cohort based on the same inclusion and exclusion criteria.Results:Among the 64 variables with<50%missing values,the recursive feature elimination method with a random forest model was used to screen the selected variables.The highest accuracy was obtained following the selection of 10 scalars,and the final model was constructed accordingly.XGBoost demonstrated the best performance comprehensively.The AUC-ROC of this model was 0.981,with an accuracy,sensitivity,and specificity of 0.939,0.950,and 0.927,respectively.In the validation cohort,the AUC-ROC,accuracy,sensitivity,and specificity of the XGBoost model were 0.702,0.718,0.636,and 0.725,respectively.The rate of major bleeding events has a positive correlation with the bleeding risk score quintiles.To allow for convenient clinical application,a smartphone application was developed for easy access and calculation(http://fir.master-wx.com/sghr).Conclusion:We successfully established a risk model and score for predicting bleeding events in older patients with comorbidity,such as CHD and gastrointestinal cancer.

Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3

Objective: To investigate the effects of composite Sophora colon-soluble Capsule(CSCC) on gut microbiota-mediated short-chain fatty acids(SCFAs) production and downstream group 3 innate lymphoid cells(ILC3s) of dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) mice model. Methods: The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry(UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups(n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s r DNA and gas chromatography-mass spectrometry(GC-MS) analysis. The expression levels of NCR^(+)ILC3^(-), CCR6^(+)Nkp46-(Lti) ILC3^(-), and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively. Results: The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus(P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR^(+) ILC3s were significantly elevated in the CSCC group(P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR^(+)ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function. Conclusion: CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR^(+)ILC3s and Lti ILC3s.

Extracts from Huangqi(Radix Astragali Mongoliciplus) and Ezhu(Rhizoma Curcumae Phaeocaulis) inhibit Lewis lung carcinoma cell growth in a xenograft mouse model by impairing mitogen-activated protein kinase signaling, vascular endothelial growth factor prod

OBJECTIVE: To study the anti-tumor effects of the extracts from Huangqi(Radix Astragali Mongolici)and Ezhu(Rhizoma Curcumae Phaeocaulis) on the growth of Lewis lung carcinoma(LLC) in a xenograft mouse model and to investigate the possible underlying mechanism.METHODS: LLC tumor-bearing C57 BL/6 mice were treated with normal saline, cisplatin(2 mg/kg intraperitoneally every other day), or Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis)(1∶1, 2∶1, or 3∶1 ratio;5, 8, or 11 g/kg crude drug intragastrically every day) for 15 d.Body weights and tumor volumes were measured every other day. Tumors were excised on day 15 and analyzed. Tumor microvessel density(MVD)was assessed by immunohistochemical staining of CD34;and expression of vascular endothelial cell growth factor(VEGF), the mitogen-activated protein kinases p38 mitogen-activated protein kinase(MAPK), extracellular signal-regulated kinases 1 and 2(ERK1/2), and Jun N-terminal kinase(JNK)and their phosphorylated forms were assessed by Western blotting.RESULTS: Treatment with cisplatin caused a significant loss of body weight compared with controls,whereas Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) extract combinations had no effect. Extracts from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) significantly decreased tumor weight and tumor MVD compared with controls,and at the 3∶1 treatment group had similar efficacy to cisplatin in reducing MVD. Tumors from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) treatments also showed decreased p38 MAPK, p-p38 MAPK, ERK1/2, p-ERK1/2,JNK, and p-JNK expression compared with the control group(all P < 0.01). VEGF protein expression was significantly reduced in the 2∶1 and 3∶1 treatment groups compared with the control group(P < 0.01).CONCLUSION: Extracts from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) hindered LLC growth in the xenograft mouse model, possibly via inhibition of the MAPK signaling pathway, VEGF production, and tumor angiogenesis.