Objective To study the effect of lipopolysaccharide(LPS)-induced M1 polarization of macrophages on tumor growth.Methods Female Balb/c mice were randomly divided into control group and experimental group.Renca cells were used to establish subcutaneous tumor model.NaCl(100μl/mice,once every two days)or LPS(100μg/mice,once every two days)was injected to the tumor side when the tumor grew to 50mm3.The M1 polarization level of tumor-associated macrophages was detected by flow cytometry.Mouse tumor cell lines(ML-1,MC38,Renca)were divided into three groups:blank group(complete medium with 50％DMEM basal medium),control group(complete medium with 50％medium supernatant of cultured macrophages)and experimental group(complete medium with 50％medium supernatant of LPS pretreated cultured macrophages).The proliferation of tumor cells was detected by cell counting kit-8(CCK-8).The cell cycle and apoptosis of tumor cells were detected by flow cytometry.Results The proportion of tumor-associated macrophages M1 increased after LPS treatment(P<0.001),thus enhancing its anti-tumor function.LPS-induced M1 polarization of macrophages can significantly inhibit the proliferation of tumor cells(Renca:P=0.023,ML-1:P=0.045).LPS-induced M1 polarization of macrophages blocked G0/G1 phase(MC38:P=0.011,ML-1:P=0.022)or S phase(Renca:P=0.022)of tumor cell cycle,and then cell division was inhibited.LPS-induced M1 polarization of macrophages significantly induced apoptosis of tumor cells(Renca:P=0.04,ML-1:P=0.007).Conclusion LPS can play an anti-tumor role by inducing M1 polarization of macrophages.

Objectives:To report the sexual functional outcomes of vaginal dilation therapy in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients.Methods:From March 2020 to February 2023, 97 MRKH syndrome patients performed vaginal dilation therapy with guidance from Peking Union Medical College Hospital, and 45 of them engaged in penetrative intercourse and were included in this prospective cohort study. The Chinese version of female sexual function index (FSFI) was used to assess sexual function. Functional success was defined as FSFI>23.45. Forty age-matched healthy women were selected as controls. Kaplan-Meier survival analysis was used to calculate the median time to success. Pearson correlation analysis was used to explore the relationship between neovagina length and sexual function. Complications were collected using follow-up questionnaires.Results:The functional success rate of vaginal dilation therapy was 89% (40/45) with a median time to success of 4.3 months (95% CI: 3.0-6.1 months). Compared to controls, MRKH syndrome patients had significantly lower scores in the orgasm domain (4.72±1.01 vs 4.09±1.20; P=0.013) and pain domain (5.03±0.96 vs 4.26±0.83; P<0.001). However, there were no significant differences in the FSFI total score (26.77±2.70 vs 26.70±2.33; P=0.912), arousal domain (4.43±0.77 vs 4.56±0.63; P=0.422) and satisfaction domain (4.88±0.98 vs 4.65±0.86; P=0.269) between MRKH syndrome patients and controls. MRKH syndrome patients had significantly higher scores in the desire domain (3.33±0.85 vs 3.95±0.73; P<0.001) and lubrication domain (4.37±0.56 vs 5.20±0.67; P<0.001). The prevalence of sexual dysfunction in MRKH patients was non-inferior to controls: low desire [3% (1/40) vs 23% (9/40); P=0.007], arousal disorder [3% (1/40) vs 3% (1/40); P>0.999], lubrication disorder [5% (2/40) vs 25% (10/40); P=0.012], orgasm disorder [40% (16/40) vs 20% (8/40); P=0.051], sexual pain [30% (12/40) vs 15% (6/40); P=0.108]. Conclusions:MRKH syndrome patients undergoing non-invasive vaginal dilation therapy could achieve satisfactory sexual life. Given its high functional success rate and slight complication, vaginal dilation therapy should be recommended as the first-line option, reducing the need for unnecessary surgeries.

Objective:To preliminarily predict the potential pathways and targets of Xiaoban Tongmai Formula in anti-atherosclerosis(AS)by network pharmacology analysis,and to verify its possible mechanism combined with in vitro cell experiment.Method:The databases including Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),GeneCards,Swiss Target Prediction,and Uniprot were used to collect the information on active compounds and corresponding targets of Xiaoban Tongmai Formula to construct the"compound-target-disease"network.The potential targets and pathways were predicted by protein-protein interaction(PPI)network,and the intersection targets were subjected to Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The human aortic vascular smooth muscle cells(HA-VSMCs)were cultured and identified in vitro,and the abnormal proliferation of HA-VSMCs were induced by oxidized low-density lipoprotein(ox-LDL)and identified;MTT method was used to detect the proliferation activities of the HA-VSMCs in various groups after treated with different concentrations of Xiaoban Tongmai Formula;the safety of Xiaoban Tongmai Fang was confirmed.The HA-VSMCs were divided into blank group,model group(the abnormal proliferation of HA-VSMCs was induced),rosuvastatin group(treated with 4 μmol·L-1 rosuvastatin after inducing the abnormal proliferation of HA-VSMCs),and low,medium,and high doses of Xiaoban Tongmai Formula groups(treated with 0.025,0.050,and 0.100 mng·L-1 Xiaoban Tongmai Formula after inducing the abnormal proliferation of HA-VSMCs);enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of monocyte chemotactic protein-1(MCP-1),interleukin-6(IL-6),and interleukin-8(IL-8)in supernatant of the HA-VSMCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of nuclear factor kappa-B(NF-κB)p65 mRNA and fibroblast growth factors 2(FGF2)mRNA in the HA-VSMCs in various groups;Western blotting method was used to detect the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in various groups.Results:Xiaoban Tongmai Formula contained 103 active ingredients that exert anti-AS effect by acting on 189 target genes.The potential targets included IL-6,IL-8,vascular endothelial growth factor A(VEGFA),nuclear factor kappa B1(NF-κB1),and RELA(NF-κB p65).The GO functional analysis and KEGG pathway enrichment analysis results showed that Xiaoban Tongmai Formula exerted anti-AS effects by regulating lipid metabolism,hypoxia-inducible factor-1(HIF-1),epidermal growth factor(EGF),phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),and NF-κB signaling pathways.The cell morphology and immunofluorescence staining results confirmed that the cells were HA-VSMCs.The oil red O staining results showed numerous red lipid droplets,indicating successful modeling.The MTT assay results showed that Xiaoban Tongmai Formula had no significant effect on the proliferation rate of HA-VSMCs within a certain dose range,indicating good safety.The ELISA results showed that compared with model group,the levels of MCP-1 and IL-6 in supernatant of the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.05 or P＜0.01),and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the levels of MCP-1 in supernatant of the HA-VSMCs in different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01).Compared with model group,the expression levels of NF-κB p65 mRNA in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the expression levels of FGF2 mRNA in the HA-VSMCs in rosuvastatin group and 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the expression levels of NF-κB p65 and FGF2 mRNA in the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.05 or P＜0.01).Compared with model group,the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the expression levels of NF-κB p65 protein in the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the expression level of FGF2 protein in the HA-VSMCs in 0.100 mg·L-1 Xiaoban Tongmai Formula group was decreased(P＜0.01).Conclusion:Xiaoban Tongmai Formula has anti-inflammatory effect,inhibitory effect on the proliferation of HA-VSMCs,and anti-AS effect,and its mechanism may be related to the inactivation of NF-κB/FGF2 pathway.

【Objective】 To explore the characteristics of white matter degeneration in amyotrophic lateral sclerosis (ALS) patients with different onset and spreading patterns by using diffusion tensor imaging (DTI). 【Methods】 We enrolled 86 ALS patients and 44 healthy controls. The patients were divided into bulbar- and spinal-onset subgroups according to their onset site, as well as horizon, vertical, interpose/skip, and caudal-rostral subgroups based on the spreading direction of the involved regions. The white matter fiber tracts corresponding to the motor network were set as the region of interest. We used tract-based spatial statistics to evaluate differences between the above groups and the normal controls, with family-wise error (FWE) correction and P<0.05 as statistical significance. 【Results】 The white matter degeneration of ALS patients with bulbar onset was mainly limited to the corona radiation part of the corticospinal tract, while those with spinal onset showed extensive degeneration of corticospinal tract and corpus callosum Ⅲ area (FWE correction, P<0.05). In patients with horizontal and vertical dissemination, decreased integrity of the entire corticospinal tract was found, with patients in the latter group showed extra degeneration in the Ⅲ part of the corpus callosum. Restricted degeneration of the corticospinal tract within bilateral corona radiata was detected in patients with caudal-rostral and interposed/skip spreading pattens (FWE correction, P<0.05). 【Conclusion】 Different onset and disease spread patterns of ALS patients correspond to divergent brain degeneration patterns. The diagnosis, treatment, and management of ALS should fully consider the heterogeneity of the disease.

【Objective】 To investigate changes in thalamus structure and function and their associations with cognitive impairment in patients with amyotrophic lateral sclerosis (ALS). 【Methods】 3D high-resolution structural imaging and resting-state fMRI were applied in 78 ALS patients and 49 healthy volunteers. The shape of the thalamus was assessed using a vortex analysis and functional connectivity between the thalamus subregion and cortex was evaluated by a seed-based correlation analysis. Partial correlation analysis was used to evaluate the correlation between focal thalamus alterations and clinical assessments. 【Results】 Compared with the control group, vertex analysis showed significant atrophy in the prefrontal and temporal subregions of bilateral thalamus in the ALS group. Patients exhibited increased functional connectivity of motor-sensory ROI with the right motor cortex, of temporal ROI with the bilateral lateral occipital cortex, precuneus and right temporal subregion. In contrast, decreased function connectivity was found mainly between temporal ROI and paracingulate gyrus, left dorsomedial prefrontal lobe and left caudate. Partial correlation analysis showed that the functional connectivity of the precuneus, paracingulate cortex, left caudate nucleus and left prefrontal lobe was correlated with multiple cognitive performances. 【Conclusion】 Selective damage of thalamic structure and function in ALS plays an important role in cognitive and behavioral disorders.

BACKGROUND: Limited data are available on the changes in the quality of care for ST elevation myocardial infarction (STEMI) during China's health system reform from 2009 to 2020. This study aimed to assess the changes in care processes and outcome for STEMI patients in Henan province of central China between 2011 and 2018. METHODS: We compared the data from the Henan STEMI survey conducted in 2011-2012 ( n = 1548, a cross-sectional study) and the Henan STEMI registry in 2016-2018 ( n = 4748, a multicenter, prospective observational study). Changes in care processes and in-hospital mortality were determined. Process of care measures included reperfusion therapies, aspirin, P2Y12 antagonists, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Therapy use was analyzed among patients who were considered ideal candidates for treatment. RESULTS: STEMI patients in 2016-2018 were younger (median age: 63.1 vs . 63.8 years) with a lower proportion of women (24.4% [1156/4748] vs . 28.2% [437/1548]) than in 2011-2012. The composite use rate for guideline-recommended treatments increased significantly from 2011 to 2018 (60.9% [5424/8901] vs . 82.7% [22,439/27,129], P <0.001). The proportion of patients treated by reperfusion within 12 h increased from 44.1% (546/1237) to 78.4% (2698/3440) ( P <0.001) with a prolonged median onset-to-first medical contact time (from 144 min to 210 min, P <0.001). The use of antiplatelet agents, statins, and β-blockers increased significantly. The risk of in-hospital mortality significantly decreased over time (6.1% [95/1548] vs . 4.2% [198/4748], odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.50-0.88, P = 0.005) after adjustment. CONCLUSIONS Gradual implementation of the guideline-recommended treatments in STEMI patients from 2011 to 2018 has been associated with decreased in-hospital mortality. However, gaps persist between clinical practice and guideline recommendation. Public awareness, reperfusion strategies, and construction of chest pain centers need to be further underscored in central China.
Humans ; Female ; Middle Aged ; ST Elevation Myocardial Infarction/drug therapy* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Cross-Sectional Studies ; Aspirin/therapeutic use* ; Platelet Aggregation Inhibitors/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use* ; Hospital Mortality ; Registries ; Treatment Outcome ; Percutaneous Coronary Intervention

Objective:To assess the effects of intervention measures on the quality control of health examination institutions in Dalian City.Methods:This cross-sectional study encompassed a comprehensive evaluation of 40 physical examination institutions in Dalian City. Interrupted time series analysis was employed to examine the changes in level and slope of processing rates for significant abnormal health examination results, chief inspection physician qualification rates, and completion rates of basic health examination items before (January 2020 to July 2021) and after (August 2021 to July 2022) intervention. An interrupted time series analysis diagram was generated.Results:After the implementation of intervention measures, the processing rate of significant abnormal results in public physical examination institutions reached 93.52%, while the qualification rate of chief inspection physicians was as high as 98.86%. And completion rate of basic health examination items was 93.86%. The rates of handling important abnormal results in health check-ups at private healthcare institutions before intervention, 1 month after intervention, and long-term intervention showed an upward trend of 1.374%, 0.229%, and 0.664%, respectively ( t=8.61, 12.21, and 108.61, all P<0.05). The qualification rate of chief inspection physicians in public physical examination institutions exhibited an increase of 0.227% and 0.155% before and after the intervention respectively ( t=6.74 and 617.67, all P<0.05). The completion rates of basic health check-up items in public healthcare institutions showed an upward trend before intervention, 1 month after intervention, and long-term intervention, with a rate of 0.446%, 0.067%, and 0.745%, respectively ( t=24.95, 3.25, 138.80, all P<0.05). Conclusions:The implementation of quality control intervention measures for health check-ups has significantly improved the quality control of health examination institutions in Dalian City.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Objective:To establish the reference for serum metabolomics profiles among healthy Han adults in China, and explore the variation on metabolomics profiles by geographic regions, sex, and age.Methods:Cross-sectional data and serum samples were obtained from the China National Health Survey. A total of 1 039 male and 1 032 female healthy adults(≥30 years) were included in this study. Serum metabolomics analyses were conducted with ultra-performance liquid chromatography-mass spectrometry(UPLC-MS). Orthogonal partial least squares discriminant analysis(OPLS-DA) was performed to compare the differences of metabolomics among different region, sex, and age.Results:Significant differences on metabolomics profiles were identified among region, sex, and age. A total of 114 region-related metabolites were spotted, including 53 metabolites that involved in human metabolic pathways, mainly peptides(20 metabolites) and glycerophospholipid metabolism-related(14 metabolites). Fifty-nine metabolites were pinned down to be sex-related, among which cotinine was significant in all 7 provinces. Age-related metabolites were only found in Shaanxi and Hainan, with 22 metabolites were recognized.Conclusion:Serum metabolomics varies by geographic regions, sex, and age. When metabolomics is applied for diagnosis or biomarker screening in various studies, it shall take into consideration of setting tailored references.

Esophageal cancer is a type of upper gastrointestinal malignant tumor with a high degree of malignancy， strong invasion ability， and poor prognosis， which belongs to the category of "dysphagia" in traditional Chinese medicine （TCM）. In addition to tumor resistance， Chinese herbal prescription plays a role in sensitization. In light of information in literature， the syndrome elements of esophageal cancer include Qi stagnation， phlegm， Qi deficiency， blood stasis， and Yin deficiency. After clinical differentiation， the syndromes of esophageal cancer are divided into phlegm and Qi obstruction， Qi and Yin deficiency， fluid deficiency and heat accumulation， Qi deficiency and phlegm dampness， combined phlegm and heat， combined phlegm and stasis， combined heat toxin and stasis， healthy Qi deficiency and toxin accumulation， et al. Dabanxiatang， Qigesan， Xuanfu Daizhetang， Liujunzitang， Shashen Maidongtang， and Tongyoutang are the common clinical prescriptions， where Qigesan， Liu Junzitang， and Tongyoutang have been proved by in vitro and in vivo experiments to exert anti-esophageal cancer effect by directly inhibiting tumor cell proliferation， promoting apoptosis， affecting tumor microenvironment， regulating cell energy metabolism， and inhibiting angiogenesis. In addition， an increasing number of studies have been conducted on anti-esophageal cancer effect of Chinese herbal prescription by targeting non-coding single-stranded microRNA. The specific mechanisms of Da Banxiatang， Shenzhe Peiqitang， Xiao Xianxiongtang， Renshen Banxiatang， and Liushenwan have been scarcely reported despite good clinical efficacy. Wuzhuyu Tang and Tongguansan recorded in ancient books have been rarely applied in modern times. Therefore， the present study reviewed the special drugs and prescriptions mentioned in ancient TCM classics， the commonly used Chinese herbal prescriptions in modern clinical practice， and experimental research progress， to promote treatment methods of Chinese herbal prescriptions against esophageal cancer.