Objective To explore the evidence,urinary biomarkers,and partial mechanisms of hypercoagulability in the pathogenesis of IgA vasculitis(IgAV).Methods Differential expression of proteins in the urine of 10 healthy children and 10 children with IgAV was screened using high-performance liquid chromatography-tandem mass spectrometry,followed by Reactome pathway analysis.Protein-protein interaction(PPI)network analysis was conducted using STRING and Cytoscape software.In the validation cohort,15 healthy children and 25 children with IgAV were included,and the expression levels of differential urinary proteins were verified using enzyme-linked immunosorbent assay.Results A total of 772 differential proteins were identified between the IgAV group and the control group,with 768 upregulated and 4 downregulated.Reactome pathway enrichment results showed that neutrophil degranulation,platelet activation,and hemostasis pathways were involved in the pathogenesis of IgAV.Among the differential proteins,macrophage migration inhibitory factor(MIF)played a significant role in neutrophil degranulation and hemostasis,while thrombin was a key protein in platelet activation and hemostasis pathways.PPI analysis indicated that thrombin directly interacted with several proteins involved in inflammatory responses,and these interactions involved MIF.Validation results showed that compared to healthy children,children with IgAV had significantly higher urine thrombin/creatinine and urine MIF/creatinine levels(P<0.05).Conclusions Thrombin contributes to the pathogenesis of IgAV through interactions with inflammatory factors.Urinary thrombin and MIF can serve as biomarkers reflecting the hypercoagulable and inflammatory states in children with IgAV.

ObjectiveThe aim of this study is to investigate the role of salidroside in regulating the miR-1343-3p/MAP3K6 （mitogen-activated protein kinase kinase kinase 6）/MMP24 （membrane-type matrix metalloproteinase 24） signaling pathway to inhibit gastric cancer cell proliferation and migration. MethodsHuman gastric cancer cells （MGC-803） were divided into several groups based on different salidroside concentrations： a control group （0 μmol/mL）， a low-dose group （6 μmol/mL）， a medium-dose group （12 μmol/mL）， and a high-dose group （24 μmol/mL）. The anti proliferative effects of salidroside on human gastric cancer cells were evaluated by CCK-8 assay. Clonogenic assay was used to examine the effects of salidroside drugs on the clonogenic ability of human gastric cancer cells. Transwell assay was performed to detect the effect of salidroside on the invasive ability of human gastric cancer cells. Cell scratch assay was performed to detect the effect of salidroside on the migration ability of human gastric cancer cells. The miRNA expression profile was analyzed by using RNA-seq in cancer cells for 24 h after salidroside treatment. The differentially expressed miRNAs were clustered and their target genes were predicted. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） were used to analyze and predict the functions of these target genes， and the interaction networks were established. Immunocytofluorescence was used to detect the expression of target proteins， and the transcription of candidate genes was detected by q-PCR. ResultsCCK-8 cytotoxicity experiments showed that salidroside inhibited the proliferation of MGC-803 cells （P < 0.01）. Cell cloning experiments showed that salidroside reduced the clonal formation capacity of MGC-803 cells （P < 0.000 1）. Cell invasion experiments showed that salidroside reduced the MGC-803 cell invasion capacity （P < 0.000 1）. Cell scratch experiments showed that salidroside reduced the cell migration capacity （P < 0.000 1）. RNA-seq findings showed that the expression of 44 miRNAs changed significantly after salidroside treatment in cancer cells （P < 0.05）. Bioinformatic analysis showed that there were 1 384 target mRNAs corresponding to the differentially expressed miRNAs， and the expression of the tumor suppressor miR-1343-3p was significantly upregulated after salidroside treatment （P < 0.01），and resulted in down-regulated transcription of MAP3K6 and MMP24 genes which are related to the proliferation and migration of cancer cells （P < 0.05）. Immunofluorescence experiments demonstrated that salidroside reduced protein expression levels in MAP3K6 and MMP24 genes （P < 0.000 1）. q-PCR experiments showed that salidroside reduced the mRNA expression level of MAP3K6 and MMP24 genes （P < 0.000 1）， while miRNA expression in miR-1343-3p gene was upregulated （P < 0.000 1）. ConclusionSalidroside regulates the miRNA-1343-3p/MAP3K6/MMP24 signaling molecules to inhibit proliferation and invasion of gastric cancer cells.

OBJECTIVE: Through showing the full picture of double-arm controlled clinical research and systematic review evidence in the field of orally administrated Chinese herbal medicine (CHM) for treatment of lung cancer, to provide a reference for future clinical research and to indicate a direction for future systematic reviews. METHODS: A comprehensive search of clinical controlled studies was performed regarding orally administered CHM treatment for lung cancer published from January 1970 to September 2020. The language was restricted to Chinese and English. Relevant data were extracted, the quality of systematic reviews was evaluated, and the research evidence was visually displayed. RESULTS: Randomized controlled trials were the most common type of research design. The research sample sizes were typically small. Oral CHM showed certain curative advantages in treating lung cancer. The key stages in oral CHM intervention for lung cancer are chemotherapy, radiotherapy, and late palliative treatment. The advantageous outcomes of oral CHM treatment of lung cancer are the short-term efficacy, quality of life, and adverse reactions. The perioperative stage, overall survival, pharmacoeconomic evaluation, and Chinese medicine decoctions are weak research areas. CONCLUSIONS CHM has staged and therapeutic advantages in treating lung cancer. The overall methodological quality is poor, and the level of evidence requires improvement. It is necessary to carry out large-scale, standardized, and higher-quality research in the superior and weak areas of CHM treatment of lung cancer.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Lung Neoplasms/drug therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic

Objective: To investigate the clinicopathological features of early gastric cancers after Helicobacter pylori (H. pylori) eradication. Methods: The clinical data of 26 cases of gastric cancer that were diagnosed after H. pylori eradication and 45 cases without H. pylori eradication in the 989 Hospital of the Joint Logistics Support Force of the People's Liberation Army (the former 152 Hospital), Pingdingshan, China from 2013 to 2021 were collected. The histological, immunophenotypic and clinical characteristics of the two groups were compared, and discussed with review of the related literature. Results: Among the gastric cancer patients with H. pylori eradication, there were 20 males and 6 females with a median age of 65 years (range 53 to 77 years). The cancer involved the upper part of the stomach in 12 cases, the middle part of the stomach in 4 cases, and the lower part of the stomach in 10 cases. The median diameter of the tumors was 12 mm (range 4-29 mm). According to the Paris Classification, 4 cases were 0-Ⅱa, 4 cases were 0-Ⅱb, 18 cases were 0-Ⅱc. White light endoscopy showed that the lesions were reddish to yellowish. The lesion boundary was clear in 12 cases and was unclear or gastritis-like changes in 14 cases, while the irregular microvascular structure and microsurface structure, as well as the relatively visible spinous boundary, were visible under narrow-band imaging. There were 20 cases of well-differentiated tubular adenocarcinoma, 4 cases of highly to moderately differentiated tubular adenocarcinoma, and 2 cases of well-differentiated tubular adenocarcinoma with papillary adenocarcinoma. Compared with gastric cancers without H. pylori eradication, gastric cancers diagnosed after H. pylori eradication was associated with lower nucleus-cytoplasm ratio (<50%), normal epithelial coverage on the cancer surface, mild atypical epithelial coverage on the cancer surface, elongation of non-cancerous glands in the cancer tissue and subepithelial progression of cancerous glands were higher (P<0.05). The cellular immunophenotypes were gastric type in 6 cases, intestinal type in 4 cases and gastrointestinal mixed type in 16 cases. Conclusions: The early gastric cancers diagnosed after H. pylori eradication are more subtle clinically and mostly well-differentiated tubular adenocarcinoma. The important morphological features of gastric cancer diagnosed after H. pylori eradication are decreased cytological atypia and overlying normal epithelium or mildly atypical epithelium of the cancer. Understanding and recognizing these morphological features are helpful to make correct endoscopic and pathological diagnoses.
Adenocarcinoma/pathology* ; Aged ; Female ; Gastric Mucosa/pathology* ; Helicobacter Infections/drug therapy* ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Stomach Neoplasms/drug therapy*

Objective: To investigate the clinicopathological features of very well-differentiated adenocarcinoma (VWDA) of the stomach. Methods: The clinicopathological data of 12 cases of VWDA of the stomach were collected retrospectively at the People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from January 2013 to May 2021. The histological characteristics and immunophenotypes were observed and analyzed with review of current literature. Results: There were 8 males and 4 females with a median age of 63 years (range 47 to 80 years). The tumor involved in the upper part of the stomach in 6 cases, the middle part in 2 cases, and the lower part in 4 cases. The median diameter of the tumors was 17 mm (range 5-65 mm). The tumor cells were similar to absorbent cells, Paneth cells, foveolar epithelial cells, and goblet cells. The cells were arranged in a single layer, and the nuclei were slightly enlarged and located at the base. The nuclei were fusiform to slightly irregular, with loss of nuclear polarity. Early tubular VWDA was found in 9 cases, and the tumor glands were similar to intestinal metaplasia. In two cases the tumors infiltrated into the submucosa. The lesions in the mucosa and submucosa showed the glands with cystic expansion, bending, branching, spiky and abortive growth pattern. One case of early papillary tubular VWDA was confined to the mucosal layer and composed of foveolar-type epithelial cells. There were two cases of advanced papillary tubular VWDA, which consisted of foveolar-type epithelial, pyloric glands, or mucinous neck cells and were associated with intra-lymphatic cancer embolus and lymph node metastases. Background mucosal atrophy and intestinal metaplasia were observed in all cases. Immunohistochemical staining showed intestinal type VWDA in 1 case, mixed gastrointestinal type VWDA in 9 cases, and gastric type VWDA in 2 cases. The Ki-67 proliferation index of 8 cases limited to the mucosa was 40%-70%, 2 cases of infiltration into the submucosa and 2 cases of advanced carcinoma was 10%-25%. All the tumors showed a wild type of p53 protein expression pattern and negative HER2. Adenocarcinoma or high-grade dysplasia was diagnosed on preoperative biopsy in 5 cases, and chronic atrophic gastritis with intestinal metaplasia in 7 cases. The median follow-up time was 28 months (range 12-72 months). No recurrence was found in the 10 patients with early cancer. Of the two patients with advanced carcinoma, one patient had lung metastases and the other died. Conclusions: Gastric VWDA is a rare low-grade malignancy with structural features of highly differentiated adenocarcinoma and extremely low cytological atypia. The diagnostic value of structural abnormality is significantly greater than cytological atypia. The invasive growth of irregular glands in the deep mucosa and submucosa is reliable evidence for diagnosis. The diagnosis of intramucosal VWDA is challenging and very difficult in some biopsy specimens.
Adenocarcinoma/pathology* ; Aged ; Aged, 80 and over ; Female ; Gastric Mucosa/pathology* ; Humans ; Hyperplasia/pathology* ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms/pathology*

Objective: To investigate the clinicopathological features and prognosis of cytotoxic T-cell lymphoma (CTL). Methods: The clinicopathological data of 134 CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University, the 989 Hospital of PLA Joint Logistics Support force (formerly the 152 Hospital) and the Fourth Hospital of Hebei Medical University from 2008 to 2020 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of tumor cells were assessed, and clinicopathological features and prognosis of patients were analyzed. Results: Among the 134 CTL patients, the male to female ratio was 1.7∶1.0, the median age was 49.5 years (range 3-83 years), and 100 cases (74.6%) were under 60 years old. Forty-six point nine percent of the patients (53/113) had B symptoms. Most of the patients presented with systemic superficial lymphadenopathy. According to the Ann Arbor staging system, 36.8% (39/106) of the patients were in stage Ⅰ-Ⅱ, and 63.2% (67/106) in stage Ⅲ-Ⅳ. The rate of extranodal involvement was 51.6% (66/128). Spleen was involved in 24.2% (31/128) of the cases. Morphology showed diffuse growth of abnormal lymphocytes, infiltrating and destroying normal tissue structure. Immunohistochemical staining showed that tumor cells expressed T cell antigens (CD2, CD3, CD5, and CD7), and 72.0% (77/107) of them had decreased or lost expression of one or more antigens. According to the numbers of CD4 and CD8 expression in tumor cells, 70 cases (52.2%) were grouped into CD8⁺>CD4⁺group. The expression rates of TIA-1 and granzyme B were 99.2% (119/120) and 79.8% (95/119), respectively. CD20 abnormal expression rate was 27.6% (37/134) and CD56 was negative in all cases. The median Ki-67 proliferative index was 45.0% (range 5%-80%). In situ hybridization of small RNA encoded by Epstein-Barr virus was negative. Clonal TCR gene rearrangement analysis was performed on 49 cases and was positive in all cases. Ninety-one patients were followed up for a median of 36 months (range, 1 to 240 months), and 40 of the 91 patients (44.0%) died. The twenty-three patients were in complete remission (including 13 cases with localized single extranodal mass). The 3-year and 5-year overall survival rates were 53.5% and 49.4%, respectively. Univariate analysis showed that B symptom, spleen involvement, extranodal involvement, clinical stage, CD8⁺>CD4⁺phenotype, abnormal expression of CD20 and Ki-67 proliferation index (>60%) were associated with overall survival (P<0.05). The multivariate Cox regression analyses showed that spleen involvement and CD8⁺>CD4⁺ phenotype were independent prognostic factors for overall survival in CTL patients. Conclusions: CTL are more commonly found in adult males under 60 years old, often accompanied by B symptom, with a high proportion of extranodal involvement and more CD8 positive phenotypes. Spleen involvement and CD8⁺>CD4⁺phenotype are independent predictors of CTL overall survival. Some patients with localized extranodal CTL may have a good prognosis.
Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human/genetics* ; Humans ; Lymphoma, T-Cell/pathology* ; Male ; Prognosis ; Retrospective Studies

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To observe the effects of herbal-cake-separated moxibustion on the repair of damaged vascular endothelium structure and the content of stromal cells derived factor 1 (SDF-1) in rabbits with atherosclerosis. METHODS: A total of 75 rabbits were randomly divided into a normal group, a model group, a direct moxibustion group, an atorvastatin calcium group and a herbal-cake-separated moxibustion group, 15 rabbits in each one. The rabbits in the normal group were fed with normal diet, and the remaining rabbits were fed with high-cholesterol diet for 12 weeks to prepare atherosclerotic model. Two groups of acupoints, one was "Juque" (CV 14), "Tianshu" (ST 25) and "Fenglong" (ST 40), the other one was "Xinshu" (BL 15), "Ganshu" (BL 18) and "Pishu" (BL 20), were applied in the direct moxibustion group and herbal-cake-separated moxibustion group; the two groups of acupoints were selected alternatively every other day. The moxibustion was given for 30 min per treatment, once a day for 4 weeks. The rabbits in the atorvastatin calcium group were treated with atorvastatin calcium tablets (1.96 mg•kg•d) which were crushed into powder and mixed into breakfast. After modeling, the rabbits in the normal group and model group received no treatment, and immobilized at the time when moxibustion was applied in other three groups. The levels of total cholesterol (TC) and triglyceride (TG) were measured by enzymic method; the low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric method; the morphological structure of aortic wall was observed under optical microscope; the serum level of SDF-1 was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: After treatment, compared with the normal group, the levels of TC, TG and LDL-C were significantly increased in the model group (all <0.01), and the level of HDL-C was decreased (<0.01). Compared with the model group, the levels of TC, TG and LDL-C were significantly decreased (all <0.01), and the level of HDL-C was significantly increased in the direct moxibustion group, atorvastatin calcium group and herbal-cake-separated moxibustion group (<0.01, <0.05). Compared with the normal group, the morphological structure of aortic wall was significantly damaged in the model group. Compared with the model group, the vascular endothelial structure was improved in the atorvastatin calcium group and herbal-cake-separated moxibustion group, and the pathological change of aorta endothelial in the direct moxibustion group was relieved. After treatment, compared with the model group, the level of SDF-1 was increased in the direct moxibustion group, atorvastatin calcium group and herbal-cake-separated moxibustion group (<0.05, <0.01); the level of SDF-1 in the herbal-cake- separated moxibustion group was higher than that in the direct moxibustion group (<0.05). CONCLUSION The herbal- cake-separated moxibustion can promote the expression of SDF-1 in serum and repair the damaged aortic endothelial structure.
Acupuncture Points ; Animals ; Atherosclerosis ; Endothelium, Vascular ; Hyperlipidemias ; Moxibustion ; Rabbits

Quality marker(Q-marker) is a new concept and pattern for quality control of traditional Chinese medicine(TCM),which will lead the development direction for quality control of TCM.Among them,how to characterize the overall quality attribute of TCM and its biological effect,is a critical scientific problem in the study of Q-marker.In this paper,integrated pharmacology is utilized to screen out and confirm the Q-marker from the complex system of TCM,so as to solve the critical scientific problem.System biology in vivo is firstly applied to establish the correlation of chemical fingerprints of TCM,their metabolic fingerprints,network targets,biological effects and efficacy of TCM,which is used to preliminary screen out Q-marker of TCM.Following that,a pharmacological method in vitro,including intestinal absorption in vitro coupled with bioactivity assessment,is employed to simultaneously determine the absorbed doses of TCM and evaluate their biological activity.Furthermore,data mining is utilized to establish the exact quantitative mathematic model between Q-marker of TCM and bioactivity.Meanwhile,two representative examples,including Yuanhu Zhitong tablets,Xinsuning capsules,are introduced to identify Q-marker of TCM and establish their quality standards related with bioactivity,which will be beneficial to improve the level of quality control of TCM and ensure the effectiveness and safety of clinical applications.