ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood， and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM （version 2012）. A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine （T3）， thyroxine （T4）， cyclic adenosine phosphate （cAMP）， and cyclic guanosine phosphate （cGMP）. The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database （TCMSP）， The Encyclopedia of Traditional Chinese Medicine （ETCM）， and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Furthermore， the Online Mendelian Inheritance in Man （OMIM）， GeneCards， TTD， DisGeNET， and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group， the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP， cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B₁ > saikosaponin B₂ > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A， D， B₁， and B₂ had higher VIP values. Network pharmacology predicted a total of 30 common targets， which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9， kinase insert domain receptor （KDR）， and mammalian target of rapamycin （mTOR） and higher mRNA level of mouse double minute 2 homolog （MDM2） than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome， which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E₂-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10^-3 g·kg^-1·d^-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg^-1·d^-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe²⁺）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Objective: Schizophrenia is a common mental disorder, and mitochondrial function represents a potential therapeutic target for psychiatric diseases. The role of mitochondrial metabolism-related genes (MRGs) in the diagnosis of schizophrenia remains unknown. This study aimed to identify candidate genes that may influence the diagnosis and treatment of schizophrenia based on MRGs. Methods: Three schizophrenia datasets were obtained from the Gene Expression Omnibus database. MRGs were collected from relevant literature. The differentially expressed genes between normal samples and schizophrenia samples were screened using the limma package. Venn analysis was performed to identify differentially expressed MRGs (DEMRGs) in schizophrenia. Based on the STRING database, hub genes in DEMRGs were identified using the MCODE algorithm in Cytoscape. A diagnostic model containing hub genes was constructed using LASSO regression and logistic regression analysis. The relationship between hub genes and drug sensitivity was explored using the DSigDB database. An interaction network between miRNA-transcription factor (TF)-hub genes was created using the Network-Analyst website. Results: A total of 1,234 MRGs, 172 DEMRGs, and 6 hub genes with good diagnostic performance were identified. Ten potential candidate drugs (rifampicin, fulvestrant, pentadecafluorooctanoic acid, etc.) were selected. Thirty-four miRNAs targeting genes in the diagnostic model (ANGPTL4, CPT2, GLUD1, MED1, and MED20), as well as 137 TFs, were identified. Conclusion Six potential candidate genes showed promising diagnostic significance. rifampicin, fulvestrant, and pentadecafluorooctanoic acid were potential drugs for future research in the treatment of schizophrenia. These findings provided valuable evidence for the understanding of schizophrenia pathogenesis, diagnosis, and drug treatment.

OBJECTIVE: To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer. METHODS: TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed. RESULTS: The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05). CONCLUSION Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
Animals ; Humans ; Mice ; Apoptosis ; Dendritic Cells/immunology* ; Glycyrrhizic Acid/pharmacology* ; HMGB1 Protein ; Lung Neoplasms/immunology*

Background The prevalence of osteoporosis and osteopenia is higher among underground coal miners than surface workers. The special underground work environment and unhealthy habits such as smoking, drinking, and a high-salt diet may lead to changes in bone metabolism, increasing the risk of fragility fractures and placing a heavy economic burden on individuals and society. Objective To identify potential factors influencing fragility fractures among coal miners in different working environments and to provide a basis for targeted preventive measures to reduce the occurrence of fragility fractures. Methods Male participants who attended at least one of the physical examinations in Kailuan Group between June 2006 and December 2020 were included in the study. The participants were divided into two groups based on their working environment: surface or underground. A case-control study was conducted, where patients with new fragility fractures served as the case group and participants without fragility fractures served as the control group. The two groups were matched with a case:control ratio of 1:4 by age (±1 year) and the same year of physical examination. The matching process was repeated twice, once for the surface working population and once for the underground working population. The analysis of risk factors was conducted using conditional logistic regression models. Results Among a total of 113138 employees in Kailuan Group, 82631 surface workers and 30507 underground workers were included, respectively. The number of individuals who suffered fragility fractures was 1375, accounting for 1.22% of the total population. The incidence of fragility fractures in underground workers was significantly higher than that in surface workers (1.63%>1.07%, P<0.001). The results of conditional logistic regression model showed that current smoking (OR=1.26, 95%CI: 1.05, 1.51), manual labor (OR=1.37, 95%CI: 1.06, 1.78), diabetes (OR=1.26, 95%CI: 1.04, 1.54), sinus tachycardia (OR=1.81, 95%CI: 1.23, 2.66), history of stroke (OR=1.51, 95%CI: 1.09, 2.09), education at college and above (OR=0.65, 95%CI: 0.45, 0.95), high income level (OR=0.69, 95%CI: 0.54, 0.90), elevated hemoglobin (OR=0.91, 95%CI: 0.85, 0.98), and elevated total cholesterol (OR=0.90, 95%CI: 0.82, 0.99) were associated with fragility fractures in the surface working population of coal mines; current smoking (OR=1.48, 95%CI: 1.17, 1.87), current drinking (OR=1.26, 95%CI: 1.01, 1.56), manual labor (OR=2.64, 95%CI: 1.41, 4.94), history of dust exposure (OR=1.28, 95%CI: 1.03, 1.58), and obesity (OR=0.72, 95%CI: 0.52, 0.96) were associated with fragility fractures in the underground working population of coal mines. Conclusion In preventing fragility fractures, special attention should be paid to the bone health of underground workers engaged in manual labor or having a history of dust exposure. It is important to correct their unhealthy behaviors in a timely manner, such as smoking and drinking, and to appropriately increase body weight to prevent fragility fractures. For surface workers, particular attention should be given to the high-risk group for fragility fractures, such as low family income per capita, manual labor, and having a history of stroke or diabetes; in addition, close monitoring of their resting heart rate, hemoglobin levels, and total cholesterol levels may help prevent fragility fractures.

Objective:To analysis the relationship between symptomatic knee osteoarthritis and frailty in older Chinese adults.Methods:In this retrospective study, follow-up data between 2011 and 2015 from the China Health and Retirement Longitudinal Study(CHARLS)were analyzed.Participates over 60 years old were divided into a frailty group, a pre-frailty group, and a normal group, according to the frailty phenotype.Cross-sectional analysis was conducted to examine the relationship between frailty and symptomatic knee osteoarthritis, and the role of symptomatic knee osteoarthritis in the progression of frailty in normal elderly people was further analyzed using a retrospective cohort.Results:In 2011, 5.9% of the elderly were frail and 15.1% of the elderly suffered knee pain.Univariate and multivariate regression analysis indicated that knee pain was a risk factor for frailty( OR: 1.91, 95% CI: 1.37-2.61, P<0.01).After a 4 year-follow-up, 41.7% of the normal elderly participants progressed to the frail or pre-frail state.Multivariate regression analysis suggested that knee pain was a risk factor for normal elderly people to enter the frail or pre-frail state( OR: 1.57, 95% CI: 1.00-2.45, P<0.05). Conclusions:Knee pain is one of the important risk factors for the development of frailty in the elderly.Normal elderly people with knee pain are at an increased risk of frailty or pre-frailty in later years.

Clinical and endoscopic data of 6 patients with colorectal mucosa associated lymphoid tissue (MALT) lymphoma who were diagnosed by endoscopy in the Digestive Endoscopy Center of Jiangsu Province Hospital of Chinese Medicine from January 2015 to June 2021 were retrospectively analyzed. There were 2 males and 4 females with aged from 62 to 87 years. The lesions were located in rectum in 3 cases, transverse colon in 1 case, sigmoid colon in 1 case, and sigmoid colon and rectum in 1 case. There were 1 case of polyposis type, 2 cases of inflammation type, and 3 cases of submucosal tumor type. The "tree-like appearance (TLA)" found in 5 cases. Endoscopic resection, surgery combined with chemotherapy, Helicobacter pylori eradication and follow-up were performed on 2, 1, 1 and 2 cases, respectively. Five cases had a good prognosis after 21-73 months follow-up, and 1 case had lost to follow-up. No recurrence was found in endoscopic and imaging review. Colorectal MALT lymphoma should be considered when colonoscopy detects a submucosal lesion with TLA sign on the left colon. Endoscopic resection has the potential to be a first-line treatment in the context of early diagnosis.

Objective:To improve the understanding of the clinical features of toxic encephalopathy associated with diquat poisoning.Methods:This study collected and analyzed the diagnosis and treatment process of 7 patients with acute diquat poisoning combined with central nervous system complications admitted to the First Affiliated Hospital of Zhengzhou University from April 2021 to April 2022. "Diquat" and "Poisoning" were used as keywords to search in CNKI, Wanfang database and PubMed database, and the literature of previous cases was reviewed for summary analysis.Results:Among the 7 patients in our hospital, there were 2 males and 5 females, with an average age of 31 years (range14-57) and an average dose of 23.14 g [(10-40)g]. During the treatment, 3 patients developed irritability and convulsions, 3 patients occurred coma, and one had generalized tonic-clonic seizures. Four patients died and 3 survived, of which 2 patients returned to normal life and study, and one remained abnormal mental behavior (currently in long-term follow-up). All three survivors developed neurological symptoms later than those who died, and were awake about 30 days after taking the drug.Conclusions:Toxic encephalopathy associated with diquat poisoning has rapid progression, poor prognosis and high mortality. This study found that the survival rate of patients with > 48 h of first onset of neurological symptoms is much higher than that of patients with ≤ 48 h of first onset of neurological symptoms, while sex, age, estimated oral dose, and type of presentation of neurological symptoms for the first time have little effect on the survival rate of hospital discharge. The earlier neurological symptoms appear, the greater the likelihood of a poor prognosis.

Objective:To explore the molecular mechanism of Guchang-Zhixie pill in the treatment of ulcerative colitis based on network pharmacology. Methods:Retrieve the TCMSP database to get the effective components and target genes of each drug in Guchang-Zhixie pill, and then retrieve the OMIM database Disgenet database to get disease genes, and then intersect the drug genes and disease genes to get the core genes. Used STRING database to build gene function association network, and used DAVID database to analize go enrichment and pathway enrichment of the core genes. Results:A total of 77 active ingredients and 211 targets of Guchang-Zhixie pill were obtained by TCMSP database, 914 genes of ulcerative colitis were obtained by retrieving disease gene database, 72 core genes were obtained by intersection of drug gene and disease gene. Topology analysis showed that the core targets were IL6, IL1B, MAPK1, VEGFA, MMP9, etc; Twelve enriched biological process clusters were obtained. The biological processes with more contact targets were positive regulation of RNA polymerase Ⅱ promoter transcription and positive regulation of DNA template transcription; A total of 14 enriched pathway clusters were obtained by pathway enrichment analysis, among which TNF signaling pathway and PI3K/Akt signaling pathway were closely related to inflammation and associated with more targets. Conclusion:The target and pathway of Guchang-Zhixie pill in the treatment of ulcerative colitis are preliminarily obtained through database analysis, which has provided the reference for clarifying its mechanism.

Objective:To analyze the distribution and composition characteristics of jellyfish stings in various coastal baths in Qinhuangdao City from 2017 to 2019, and to provide scientific basis for the prevention, control and early warning of jellyfish stings.Methods:Statistics and analysis of the age, gender, time of stings, location of injury, first symptoms, and playing time in the sea at the time of the sting, etc. of people with jellyfish stings in various bathing beaches along the coast of Qinhuangdao from 2017 to 2019 (July to August) were conducted.Results:The number of jellyfish stings in the coastal bathing beaches of Qinhuangdao City in 2017, 2018, and 2019 was decreasing year by year, with 1 890, 492, and 171 cases respectively. Among them, Qianshuiwan Bathing Beach and Dongshan Bathing Beach had more stings (60.90% and 35.08% respectively in 2017, 24.39% and 64.23% respectively in 2018, 16.96% and 16.42% respectively in 2019). There was no significant change in the gender and age distribution of jellyfish stings each year [57.99% males in 2017, with a median age of 13 (8, 31) years old; 63.21% males in 2018, with a median age of 25 (8, 29) years old; and 59.65% males in 2019, with a median age of 12 (7, 31) years old]. Stings were mainly located at the lower limbs (the proportion of lower limb injuries: 46.54% in 2018, 45.61% in 2019), followed by upper limbs (upper arm, elbow, forearm), trunk, etc. The first symptom was mainly pain (89.43% in 2018, 38.29% in 2019), followed by rash (64.43% in 2018, 59.43% in 2019), numbness, blisters, etc. Sting incidents mainly occurred from 13:00 to 17:59 (the proportion of sting incidents in this time period in 2018 and 2019 were 68.09% and 52.63%, respectively).Conclusions:Jellyfish stings in coastal baths in Qinhuangdao City are mainly distributed in Qianshuiwan Baths and Dongshan Baths. The management of these sea areas should be strengthened, and scientific publicity and medical rescue should be strengthened to prevent jellyfish stings in peak hours and related baths.