ObjectiveTo investigate the mechanism by which Shaoyaotang regulates the miRNA-155-mediated suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 1 （STAT1） signaling pathway and thereby affects macrophage polarization. MethodsThe cell-counting kit-8 （CCK-8） assay was used to detect the effect of drug-containing serum of Shaoyaotang at different concentrations on the viability of RAW 264.7 cells. A cell model of inflammation was established by stimulating RAW264.7 cells with lipopolysaccharide （LPS） at a concentration of 10 mg·L^-1 The modeled cells were assigned by the random number table method into seven groups： LPS-induced M1 polarization （model）， M1+miRNA-155 mimics， M1+miRNA-155 inhibitor， M1+Shaoyaotang-containing serum， M1+miRNA-155 mimics+Shaoyaotang-containing serum， M1+miRNA-155 inhibitor+Shaoyaotang-containing serum， and M1+blank serum. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］. Immunofluorescence assay was used to detect the expression of macrophage polarization markers ［inducible nitric oxide synthase （iNOS） and macrophage mannose receptor 1 （CD206）］. Real-time PCR was employed to measure the expression of miRNA-155 in cells. Western blot was performed to determine the protein levels of SOCS1， STAT1， and JAK1. ResultsCompared with the LPS-induced M1 polarization （model） group， the M1+miRNA-155 mimics group showed up-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and down-regulated expression of CD206 （P<0.05）. In both the M1+miRNA-155 inhibitor group and the M1+Shaoyaotang-containing serum group， the expression levels of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS were down-regulated （P<0.05）， while those of SOCS1 and CD206 were up-regulated （P<0.05）. Compared with the M1+miRNA-155 mimics group， the M1+miRNA-155 mimics+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and up-regulated expression of SOCS1 and CD206 （P<0.05）. Compared with the M1+miRNA-155 inhibitor group， the M1+miRNA-155 inhibitor+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and up-regulated expression of SOCS1 and CD206 （P<0.05）. ConclusionShaoyaotang regulates macrophage polarization by modulating miRNA-155 expression and interfering with the SOCS1/JAK1/STAT1 signaling pathway. The findings provide new experimental evidence for the treatment of ulcerative colitis with Shaoyaotang.

ObjectiveTo investigate the potential role and underlying mechanisms of Shaoyaotang in intervening macrophage glycolytic reprogramming in ulcerative colitis （UC）. MethodsForty-eight C57BL/6 mice were randomly divided into six groups： Normal control group， model group， mesalazine group （0.39 g·kg^-1）， Shaoyaotang group （15.54 g·kg^-1）， 2-deoxy-D-glucose （2-DG） group （glycolysis inhibitor， 100 mg·kg^-1）， and 2-DG + Shaoyaotang combined group （100 mg·kg^-1+15.54 g·kg^-1）. Except for the normal control group， mice in the other five groups were induced to establish UC models using dextran sulfate sodium （DSS）. The normal control group was administered pure water via intragastric gavage， while the other groups received intragastric gavage of mesalazine solution， intragastric gavage of Shaoyaotang， and the 2-DG group was treated with 2-DG via intraperitoneal injection. After 7 consecutive days of treatment， colonic tissues were extracted. Hematoxylin and eosin （HE） staining was performed to evaluate histopathological changes and tissue injury in the colon. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-10 （IL-10） and tumor necrosis factor-α （TNF-α） in colonic tissues. Western blot analysis was employed to determine the expression levels of hypoxia-inducible factor-1α （HIF-1α）， glucose transporter （GLUT1）， lactate dehydrogenase A （LDHA）， pyruvate kinase M2 （PKM2）， and 6-phosphofructo-2-kinase/fructose-2，6-biphosphatase 3 （PFKFB3） in colonic tissues. Immunofluorescence was conducted to detect the expression of CD206 and inducible nitric oxide synthase （iNOS） in colonic tissues. Liquid chromatography-mass spectrometry （LC-MS） was utilized to measure lactate and citrate levels in colonic tissues. ResultsCompared with the normal control group， mice in the model group exhibited a significant increase in disease activity index （DAI） scores， accompanied by colonic mucosal congestion， edema， and inflammatory cell infiltration， significantly elevated expression of the inflammatory cytokine TNF-α （P<0.05）， significantly decreased IL-10 expression （P<0.05）， significantly increased levels of HIF-1α， GLUT1， LDHA， PKM2， and PFKFB3 in colonic tissues （P<0.05）， markedly elevated iNOS expression （P<0.05）， significantly decreased CD206 expression （P<0.05）， and significantly elevated lactate and citrate levels in colonic tissues （P<0.05）. In contrast to the model group， the Shaoyaotang group， inhibitor group， and Shaoyaotang combined with inhibitor group demonstrated amelioration of mucosal injury in colonic tissues， markely decreased expression levels of the inflammatory cytokine TNF-α （P<0.05）， elevated IL-10 expression levels， significantly decreased expression of HIF-1α， GLUT1， LDHA， PKM2， and PFKFB3 （P<0.05）， markedly reduced iNOS expression levels （P<0.05）， significantly increased CD206 expression （P<0.05） and significantly decreased lactate and citrate levels （P<0.05）. ConclusionShaoyaotang ameliorates symptoms of DSS-induced UC in mice， and its therapeutic mechanism may be associated with regulating macrophage glycolytic reprogramming via modulation of the HIF-1α signaling pathway.

ObjectiveTo investigate the role of microRNA-155-5p （miR-155-5p） in ulcerative colitis （UC） and study the molecular mechanism of Shaoyaotang in the treatment of UC by regulating miR-155-5p. MethodsForty-eight SPF-grade male C57BL/6 mice were selected and assigned via the random number table method into 6 groups （n=8）： A blank control group， a model group， a mesalazine （0.39 g·kg^-1） group， a Shaoyaotang （31.08 g·kg^-1） group， a Janus kinase 1 （JAK1） inhibitor （baricitinib， 10 mg·kg^-1） group， and a Shaoyaotang combined with inhibitor （baricitinib 10 mg·kg^-1 + Shaoyaotang 31.08 g·kg^-1） group. After successful modeling of UC by gavage of 3% dextran sulphate sodium solution， each group received corresponding drug intervention for 7 days. Shaoyaotang and mesalazine were administered by gavage， and baricitinib by intraperitoneal injection. Twenty-four hours after the last administration， mice were anesthetized by intraperitoneal injection of pentobarbital sodium， and blood was collected for determination of white blood cell count and erythrocyte sedimentation rate （ESR）. Mice were then sacrificed for measurement of colon length. Hematoxylin-eosin staining was used to observe colonic pathological changes and perform pathological scoring. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the relative expression of miR-155-5p in the colonic tissue， and Western blot was used to determine the protein levels of JAK1， phosphorylated JAK1 （p-JAK1）， suppressor of cytokine signaling 1 （SOCS1）， signal transducer and activator of transcription 1 （STAT1）， and phosphorylated STAT1 （p-STAT1）. ResultsCompared with the blank control group， the model group showed increased disease activity index （DAI） score and pathological score， shortened colon， upregulated relative expression of miR-155-5p and protein levels of p-JAK1 and p-STAT1， downregulated protein level of SOCS1 in the colonic tissue， prolonged time of erythrocyte sedimentation， and increased white blood cell count （P<0.01）. Compared with the model group， all drug-treated groups exhibited improvements in the above indicators （P<0.01）. Moreover， the Shaoyaotang group showed better therapeutic effects than the mesalazine group in regulating miR-155-5p expression， related protein levels， DAI score， and colonic pathological score （P<0.01）. ConclusionShaoyaotang may downregulate miR-155-5p to relieve its inhibition on SOCS1， thereby suppressing the excessive activation of the JAK1/STAT1 signaling pathway and ultimately alleviating intestinal inflammatory damage.

Abdominal aortic aneurysm (AAA) is an extremely dangerous aortic dilating disease, with a high mortality rate once ruptured. With the advancement of imaging techniques such as computed tomography angiography (CTA), the detection rate of this disease has increased correspondingly. Early detection and timely treatment are crucial for reducing mortality and improving patient prognosis. Compared to traditional open surgery, endovascular aortic repair (EVAR) for AAA is minimally invasive, using a stent graft to isolate the aneurysm sac as a whole, preventing arterial blood from entering the sac and further preventing the aneurysm from progressing or rupturing. Due to the characteristics of EVAR, precise preoperative assessment of AAA anatomy is required to develop a surgical plan for selecting the appropriate stent diameter and length. However, current attention on preoperative assessment of EVAR is more focused on the neck landing zone of the aneurysm, its shape, calcification, etc., while there is relatively less attention and lack of uniform standards for the selection and positioning judgment of the distal landing zone of the iliac artery. And, a growing number of studies have shown that improper treatment of the distal landing zone may lead to complications such as type Ⅰb endoleak and restenosis after stent implantation, affecting the prognosis of patients. This article provides a review of the current domestic and international methods and progress in the preoperative assessment of the distal landing zone for EVAR.

Abdominal aortic aneurysm (AAA) is an extremely dangerous aortic dilating disease, with a high mortality rate once ruptured. With the advancement of imaging techniques such as computed tomography angiography (CTA), the detection rate of this disease has increased correspondingly. Early detection and timely treatment are crucial for reducing mortality and improving patient prognosis. Compared to traditional open surgery, endovascular aortic repair (EVAR) for AAA is minimally invasive, using a stent graft to isolate the aneurysm sac as a whole, preventing arterial blood from entering the sac and further preventing the aneurysm from progressing or rupturing. Due to the characteristics of EVAR, precise preoperative assessment of AAA anatomy is required to develop a surgical plan for selecting the appropriate stent diameter and length. However, current attention on preoperative assessment of EVAR is more focused on the neck landing zone of the aneurysm, its shape, calcification, etc., while there is relatively less attention and lack of uniform standards for the selection and positioning judgment of the distal landing zone of the iliac artery. And, a growing number of studies have shown that improper treatment of the distal landing zone may lead to complications such as type Ⅰb endoleak and restenosis after stent implantation, affecting the prognosis of patients. This article provides a review of the current domestic and international methods and progress in the preoperative assessment of the distal landing zone for EVAR.

Objective : To analyze the trends in mortality and life lost due to bladder cancer in Suzhou City, Jiangsu Province from 2003 to 2022, so as to provide the reference for prevention and treatment strategy of bladder cancer. Methods: The data of bladder cancer death in Suzhou City from 2003 to 2022 were collected through Suzhou Residents' Death Registration System, including age, gender, date of death and underlying cause of death. The crude mortality, standardized mortality, years of potential life lost (PYLL), standardized years of potential life lost (SPYLL), years of potential life lost rate (PYLLR), standardized years of potential life lost rate (SPYLLR) and average years of life lost (AYLL) were calculated. The average annual percent change (AAPC) was used to analyze the trends in bladder cancer death and life lost. Results: Totally 2 978 deaths occurred due to bladder cancer in Suzhou City from 2003 to 2022. The crude mortality was 2.22/105, which appeared a tendency towards a rise (AAPC=4.271%, P<0.05). The standardized mortality was 0.91/105, which appeared no significant changing trend (P>0.05). The standardized mortality was 1.58/105 in males and 0.37/105 in females, which appeared no significant tendency in males (P>0.05) and appeared a tendency towards a decline in females (AAPC=-2.331%, P<0.05). The age-specific crude mortality was low among people who aged under 45 years, began to rise among people aged over 45 years and peaked among people aged 60 years and older. The crude mortality of bladder cancer in males aged 60 years and older showed an increasing trend (AAPC=2.864%, P<0.05), but there was no significant tendency in females aged 60 years and older (P>0.05). The PYLL, SPYLL, PYLLR, SPYLLR and AYLL of bladder cancer were 5 020.00 person-years, 2 945.14 person-years, 0.04‰, 0.03‰ and 9.07 years per person. SPYLL, SPYLLR and AYLL showed an decreasing trend (AAPC=-2.867%, -3.321%, -3.738%, P<0.05). Conclusions The mortality of bladder cancer in Suzhou City appeared a tendency towards a rise from 2003 to 2022. The PYLL appeared a downward trend. Males aged 60 years and older are the key groups for the prevention and control of bladder cancer.

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the "m6A site methylation stoichiometry" of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3'-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.
Humans ; Bone Marrow/metabolism* ; Bone Morphogenetic Proteins/metabolism* ; Dental Implants/adverse effects* ; Diabetes Mellitus, Type 2/metabolism* ; Growth Differentiation Factors/metabolism* ; Mesenchymal Stem Cells/metabolism* ; RNA/metabolism* ; RNA Processing, Post-Transcriptional

Objective:To investigate the expression of circular RNA circOMA1 in children with acute myeloid leukemia (AML) and to investigate the effect and mechanism of circOMA1 on the cell proliferation and apoptosis of human acute monocytic leukemia cells (THP-1).Methods:Bone marrow samples of 14 children with AML at the initial diagnosis and after complete remission were collected as the initial diagnosis group and remission group, and bone marrow samples from 10 children without tumor or malignant blood disease in the same hospital and the same period were enrolled as the control group.Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of circOMA1, miR-145 and myelocytomatosis viral oncogene homolog (MYC) mRNA in clinical AML samples and THP-1 cell line.The cells transfected with THP-1 were divided into groups, the cells transfected with circOMA1 alone (circOMA1 high expression group) were transfected with pcDNA3.1 empty vector cells as control (pcDNA3.1 control group); the cells co transfected with circOMA1 and miR-145 (circOMA1+ miR-145 group) were treated with pcDNA3.1 and miR-NC co transfected cells were used as control (pcDNA3.1+ miR-NC group, circOMA1+ miR-NC group). Cell counting kit (CCK8) was adopted to detect the effects of circOMA1 and miR-145 on the cell proliferation of THP-1.The effects of circOMA1 and miR-145 on cell apoptosis of THP-1 were detected using flow cytometry, and the effects of circOMA1 and miR-145 on MYC protein expression was detected via Western blot.The comparison between groups was analyzed by independent sample t-test or paired sample t-test, and the correlation was analyzed by Pearson correlation. Results:The expression of circOMA1 in the initial diagnosis group(4.408±3.607) was significantly increased compared with that in the control group (0.998±0.560) ( t=2.946, P<0.01); the expression of circOMA1 in remission group(1.582±0.950) was significantly decreased compared with that in the initial diagnosis group( t= 3.628, P<0.01). The THP-1 cell experiments showed that compared to the pcDNA3.1 control group, the expression of miR-145 in the circOMA1 high expression group decreased ( t= 4.21, P<0.05), cell proliferation was enhanced at 72 h and 96 h ( t=5.46, 7.40, all P<0.05), apoptosis was inhibited( t=6.44, P<0.01). The expression of MYC protein in circOMA1+ miR-NC group was higher than that of pcDNA3.1+ miR-NC group( t=5.72, P<0.01), the expression of MYC protein in circOMA1+ miR-145 group was lower than that in circOMA1+ miR-NC group ( t=4.56, P<0.05); at 72 h and 96 h, the cell proliferation level of circOMA1+ miR-NC group was higher than that of pcDNA3.1+ miR-NC group ( t=5.77, 7.30, all P<0.05), the level of cell proliferation in circOMA1+ miR-145 group was lower than that in circOMA1+ miR-NC group ( t=4.66, 6.17, all P<0.05); the apoptosis rate of circOMA1+ miR-145 group was higher than that of circOMA1+ miR-NC group ( t=4.25, P<0.05). circOMA1 expression was negatively correlated with miR-145 expression ( r=-0.62, P=0.016) and positively correlated with MYC gene expression ( r=0.64, P=0.013) in clinical samples. Conclusions:circOMA1 is highly expressed in children with AML, and can promote AML cell proliferation and inhibit apoptosis through miR-145/MYC pathway, which provides a basis for AML therapy and diagnosis.

Objective:To understand the distribution and epidemiological characteristics of chronic lymphocytic leukemia (CLL) in Hunan Province.Methods:According to the audit methods and evaluation criteria specified by the National Cancer Registration Center, the registration data of CLL reported by 24 tumor registries was included. Through the research method of retrospective analysis, the selected registry data was calculated and analyzed according to the year, administrative division, urban and rural areas, gender and age.Results:A total of 104 newly diagnosed CLL patients were diagnosed in Hunan Province from 2014 to 2015, with an average annual morbidity of 0.39/100, 000. The morbidity in 2014 and 2015 was 0.39/100, 000 and 0.39/100, 000, respectively. The annual average morbidity in Zhuzhou was 0.8/100, 000, which was the highest among municipalities. The annual average morbidity in Kaifu District of Changsha was 1.65/100, 000, which was the highest among district-level administrative divisions. The morbidity of urban was higher than that of rural (Urban vs Rural, P=0.006). The male to female morbidity was 1.7∶1. The cases were mainly concentrated in the 61-70-year-old population, accounting for 33.65% of all cases (35/104). There were 64 patients died of CLL in Hunan Province from 2014 to 2015, and the average annual mortality was 0.24/100, 000. The mortality in 2014 and 2015 was 0.22/100, 000 and 0.26/100, 000, respectively. The average annual mortality in Hengyang was 0.53/100, 000, which was the highest among municipalities. The average annual mortality in Furong District of Changsha was 0.74/100, 000, which was the highest among district-level administrative divisions. The mortality of urban was higher than that of rural but with no significant difference ( P=0.006). The male to female mortality rate was 1.4∶1. The deaths were mainly concentrated in the 71-80-year-old population, accounting for 29.69% of all deaths (19/64). Conclusions:The morbidity of CLL in Hunan Province is much lower than that of European and American populations, and it mainly occurs in the elderly people. It is more common in men. The morbidity of urban is higher than that of rural and morbidity in Zhuzhou is the highest. The death of CLL patients was mainly in middle-aged and elderly population, with more males. The mortality of urban is slightly higher than that of rural and the mortality in Hengyang is the highest.

OBJECTIVE：To systematically evaluate the effectiveness and safety of Shenfu qiangxin pills combined with chemical medicine conventional therapy in the treatment of chronic heart failure ，and to provide evidence-based reference for clinical drug use. METHODS ：Retrieved from CNKI ，Wanfang database ，VIP，Google Scholar ，PubMed，the Cochrane Library and Embase database ，RCTs about Shengfu qiangxin pills combined with chemical medicine conventional therapy （trial group ） versus chemical medicine conventional treatment （control group ）were collected during the inception to May 12th，2020. After literature screening and data extraction ，the quality of the literatures was evaluated with risk bias assessment tool recommended by Cochrane 5.1.0 system evaluator manual. Meta-analysis and sensitivity analysis were performed by using Stata 14.0 software. RESULTS：A total of 7 RCTs were included ，involving 596 patients. Meta-analysis results showed that the total response rate of trial group was significantly higher than that of control group [OR ＝4.14，95％CI（2.15，7.97），P＜0.000 01]；the results of sub-group analysis according to the different criteria for determining the efficacy showed that the total response rates of trial group determined by Lee integral method and cardiac function grading method were sig nificantly higher than that of the control group （P＜0.05）. After treatment ，N-terminal pro-B-type natriuretic peptide （NT-proBNP） level of trial group was significantly lower than that of control group [OR ＝－1.33，95％CI（－1.55， qq.com －1.11），P＜0.000 01]. Results of sub-group analysis accor- ding to cardiac failure type showed that NT-proBNP level of patients with chronic heart failure in trial group was lower than control group （P＜0.001）. The level of left ventricular ejection fraction （LVEF）in trial group after treatment [WMD ＝5.76，95％CI （5.05，6.47），P＜0.000 01] was significantly higher than control group ；after treatment ，the level of B-type natriuretic peptide [SMD＝－1.61，95％CI（－2.58，－0.54），P＜0.000 01]，left ventricular end-diastolic diameter （LVEDD）level [WMD ＝ －6.06，95％CI（－6.84，－5.27），P＜0.000 01]，left ventricular end-systolic diameter level [WMD ＝－0.52，95％CI（－5.70，－4.33）， P＜0.000 01] were significantly lower than control group. There was no statistically significant difference in the incidence of ADR between 2 groups（P＞0.05）. Results of sensitivity analysis showed that when NT-proBNP ，LVEF level ，LVEDD level after treatment were used as indicators ，there was no significant difference in the analysis results after eliminating heterogeneity source ， compared with before elimination. CONCLUSIONS ：Shenfu qiangxin pills combined with chemical medicine conventional treatment has good efficacy and safety.