Objective: To elucidate the potential mechanisms by which Chinese herbal medicine (CHM) regulates gut microbiota (GM) to influence the development of primary open-angle glaucoma (POAG). Methods: Data mining, network pharmacology, and Mendelian randomization (MR) analyses (two-sample design) were conducted in integration to systematically explore the CHM-GM-POAG axis. Literature-based data mining method was applied to identify frequently used herbs and herb pairs for POAG, and the properties and meridian tropism of the herbs were analyzed as well. Target prediction and pathway enrichment analyses were performed to identify shared molecular pathways among CHM components, GM, and POAG. MR analysis was performed to assess the genetically predicted causal associations between specific microbial taxa and POAG risk. Results: Our data mining work indicated that commonly used CHMs were mainly bitter and sweet in flavors and cold in property, with meridian tropism toward the liver, lung, and kidney. The predominant therapeutic effects of the CHMs included soothing the liver and regulating Qi, promoting blood circulation, and reducing fluid retention. Representative herb pairs were Shudihuang (Rehmanniae Radix Praeparata)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma), Gouqi (Lycii Fructus)-Fuling (Poria) with Shudihuang (Rehmanniae Radix), and Juhua (Chrysanthemi Flos)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma). Network pharmacology revealed overlapping targets involving antioxidative, anti-inflammatory, and metabolic regulation pathways. MR analysis demonstrated that higher abundances of Ruminiclostridium 6 [odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.58 – 0.92, P = 0.007], Ruminococcaceae UCG-002 (OR = 0.77, 95% CI: 0.63 – 0.96, P = 0.018), Ruminococcus torques group (OR = 0.71, 95% CI: 0.57 – 0.90, P = 0.004), and Victivallis (OR = 0.82, 95% CI: 0.70 – 0.96, P = 0.016) were causally associated with reduced POAG risk, whereas Actinomyces (OR = 1.34, 95% CI: 1.06 – 1.68, P = 0.013) and Blautia (OR = 1.39, 95% CI: 1.01 – 1.90, P = 0.042) showed positive associations. Conclusion This study revealed potential causal links between GM and POAG and provided integrative evidence that CHM may modulate the microbiota to exert neuroprotective effects. These findings offer new integrative insights into the gut-eye axis and a theoretical basis for developing microbiota-targeted CHM strategies in glaucoma management.

Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Objective:To explore the prenatal ultrasound phenotype and genetic basis of two fetuses with Wolf-Hirschhorn syndrome (WHS).Methods:A retrospective analysis was conducted on the ultrasound imaging data of two fetuses suspected for WHS at the Prenatal Diagnostic Center of Qingyuan People′s Hospital in July 2017 and August 2019, respectively. Amniotic fluid samples of the two fetuses were subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). This study was approved by Medical Ethics Committee of the Qingyuan People′s Hospital (Ethics No. IRB-2022-064).Results:Prenatal ultrasound examination of the two fetuses had consistently revealed WHS-associated traits including intrauterine growth restriction (IUGR), craniofacial abnormalities and cardiovascular anomalies. Karyotyping analysis suggested that both fetuses had harbored cryptic chromosomal translocations involving partial deletion of 4p. And parental verification revealed that it was de novo for fetus 1 and paternal for fetus 2. CMA has confirmed that fetus 1 had an approximately 8.7 Mb deletion at 4p16.3p16.1 and a 6.8 Mb duplication at 8p23.1p23.1, whilst fetus 2 had a 20.05 Mb deletion at 4p16.3p15.31 and a 7.66 Mb duplication at 9p24.3p24.1. The karyotype of fetus 1 was determined as 46, XN, der(4)t(4; 8)(p16.1; p23.1)dn.arr[hg19]4p16.3p16.1(68345_8721580)×1, 8p23.3p23.1(158048_6933745)×3, and that of fetus 2 was determined as 46, XN, der(4)t(4; 9)(p15.3; p24)dpat.arr[hg19]4p16.3p15.31(68345_20116061)×1, 9p24.3p24.1(208454_7868292)×3. Conclusion:The 4p deletion is probably the main cause for the WHS phenotype in both fetuses. WHS should be suspected when IUGR, renal anomalies, craniofacial and cardiovascular abnormalities are detected upon prenatal ultrasound screening.

Objective:To understand the characteristics and trends of acute myocardial infarction (AMI) in Shandong Province and to provide evidence for formulating prevention and control strategies.Methods:Data were derived from the AMI incidence reports of Shandong Province's Chronic Disease Surveillance Information Management System in 2012-2021. The crude and standardized incidence rates were used as indicators to describe the incidence level of AMI. Joinpoint regression analysis was used to analyze the trends in the incidence and age of onset over the years. The contribution of population aging to the increase in AMI incidence was assessed using the rate difference decomposition method. The incidence of AMI in each district (county) in Shandong Province was visualized using ArcGIS 10.8 software, and global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software.Results:From 2012 to 2021, 198 233 cases of AMI were reported from 19 provincial monitoring sites in Shandong Province, of which 53.13% were males and 97.12% were ≥45 years old. The reported crude incidence increased from 90.12 per 100 000 in 2012 to 176.54 per 100 000 in 2021, with an average annual increase of 7.01% ( Z=7.35 , P<0.001). There was no significant upward trend in standardized incidence ( Z=1.64 , P=0.140), but the standardized incidence of male residents showed an increasing trend ( Z=2.76 , P=0.028). Before 2014, the reported crude incidence of males was similar to that of females, but after 2014, the reported crude incidence of males was continuously higher than that of females. However, males' standardized incidence was higher than females in all years. Both crude and standardized incidence rates were higher in rural residents than in urban areas. The median onset of AMI increased from 71.6 years old in 2012 to 73.5 years old in 2021. The median age of onset in males was lower than that in females in all years, and in most years, the median age of onset in urban residents was lower than that in rural residents. The incidence of AMI in males showed a trend in younger age groups. According to the seasonal decomposition, the incidence peak of AMI was in January, and the trough was in September. The contribution of aging population to the increase in crude incidence of AMI increased from 8.63% in 2013 to 52.58% in 2021. The global spatial autocorrelation analysis showed that the incidence of AMI presented an obvious spatial clustering distribution. Local spatial autocorrelation analysis found that the high-incidence areas (counties) were mainly concentrated in Liaocheng City and Dezhou City in the northwest region of Shandong Province and Heze City in the southwest. Conclusions:The incidence of AMI among residents in Shandong Province was rising, with spatial clustering and seasonal clustering characteristics. People aged 45 years and older, male residents, and rural residents were at high risk of developing AMI. There was a certain trend of younger age at onset among men. Targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustering areas in northwestern Shandong Province.

Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Objective To explore the mechanism of Sihuang powder(Radix et Rhizoma Rhei,Cortex Phellodendri,Radix Scutellariae and Fructus Gardeniae)in the treatment of knee synovitis by network pharmacology.Methods The active ingredients and corresponding targets of Sihuang powder were obtained from TCMSP database.A network diagram including medicines,active ingredients and targets was drawn by Cytoscape 3.9.1 software.The core targets were obtained by intersecting with the disease targets obtained from OMIM and Gene Cars databases.A target interaction network was constructed based on STRING database,and the GO/KEGG(gene ontology/Kyoto encyclopedia of genes and genomes)visualization analysis was performed on the core targets through DAVID database.The main chemical components and core target information were queried in TCMSP database and PDB database,and the results were imported into Autodock Tools.Autodock Vina was used for molecular docking analysis,and PyMol was used to draw 3D maps.Results A total of 68 active ingredients and 244 drug targets of Sihuang powder were obtained,including 18 core targets,such as tumor necrosis factor(TNF),interleukin-6(IL-6),protein kinase B1(AKT1)and tumor protein p53(TP53).A total of 118 signal pathways were obtained by KEGG enrichment analysis.The molecular docking results showed that quercetin,kaempferol,baicalein and wogonin in Sihuang powder had strong affinity with key targets.Conclusion Sihuang powder has the characteristics of multi-component,multi-target,and multi-pathway in the treatment of knee synovitis.It lays a foundation for further basic experimental research,and provides a reference for the exploration of the mechanism of this prescription in the treatment of knee synovitis.

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Objective To explore the aptamer specific binding blood group antigen-binding adhesin (BabA) of Helicobacter pylori (H.pylori) for blocking of H.pylori adhering host cell. Methods H.pylori strain was cultured and its genome was extracted as templates to amplify the BabA gene by PCR with designed primers. The BabA gene obtained was cloned and constructed into prokaryotic expression plasmid, which was induced by isopropyl beta-D-galactoside (IPTG) and purified as target. The single stranded DNA (ssDNA) aptamers that specifically bind to BabA were screened by SELEX. Enzyme-linked oligonucleotide assay (ELONA) was used to detect and evaluate the characteristics of candidate aptamers. The blocking effect of ssDNA aptamers on H.pylori adhesion was subsequently verified by flow cytometry and colony counting at the cell level in vitro and in mouse model of infection, respectively. Meanwhile, the levels of cytokines, interleukin 6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), IL-10 and IL-4 in the homogenate of mouse gastric mucosa cells were detected by ELISA. Results The genome of H.pylori ATCC 43504 strains was extracted and the recombinant plasmid pET32a-BabA was constructed. After induction and purification, the relative molecular mass (M_r) of the recombinant BabA protein was about 39 000. The amino acid sequence of recombinent protein was consistent with BabA protein by peptide mass fingerprint (PMF). Five candidate aptamers were selected to bind to the above recombinent BabA protein by SELEX. The aptamers A10, A30 and A42 identified the same site, while A3, A16 and the above three aptamers identified different sites respectively. The aptamer significantly blocked the adhesion of H.pylori in vitro. Animal model experiments showed that the aptamers can block the colonization of H.pylori in gastric mucosa by intragastric injection and reduce the inflammatory response. The levels of IL-4, IL-6, IL-8 and TNF-α in gastric mucosal homogenates in the model group with aptamer treatment were lower than that of model group without treatment. Conclusion Aptamers can reduce the colonization of H.pylori in gastric mucosa via binding BabA to block the adhesion between H.pylori and gastric mucosal epithelial cells.
Animals ; Mice ; Helicobacter pylori/genetics* ; Interleukin-4 ; Interleukin-6 ; Interleukin-8 ; Tumor Necrosis Factor-alpha ; Stomach ; Oligonucleotides ; Adhesins, Bacterial/genetics* ; Blood Group Antigens

Objective To clarify whether Helicobacter pylori (H. pylori) can promote metastasis of gastric cancer cells via the high-expression of induced B cell specific Moloney murine leukemia virus integration site 1 (Bmi-1). Methods The gastric cancer tissue specimens from 82 patients were collected for this study. The protein and gene expression level of Bmi-1 in gastric adenocarcinoma tissue were detected by immunohistochemistry and real time quantitative PCR, respectively. And meanwhile the correlation between Bmi-1 levels and pathological features, and prognosis of gastric cancer were analyzed retrospectively. Then, the GES-1 cells were transfected with pLPCX-Bmi-1 plasmid and infected with H. pylori respectively. After the Bmi-1 overexpression in GES-1 cells, the invasion ability of the GES-1 cells was detected by Transwell assay, and the cell cycle and apoptosis were detected by flow cytometry. Results The mRNA and protein of Bmi-1 expression in gastric cancer tissues were higher than tumor-adjacent tissue, and the high expression of Bmi-1 was positively correlated with tumor invasion, TNM stage, tumor differentiation, lymph node metastasis and H. pylori infection. When expression of Bmi-1 was up-regulated as a result of H.pylori infection or pLPCX-Bmi-1 transfection, the GES-1 cells had higher invasiveness and lower apoptosis rate with the above treatment respectively. Conclusion H. pylori infection can inhibit the apoptosis of gastric cancer cells and promote their invasion via up-regulating expression of Bmi-1.
Humans ; Cell Line, Tumor ; Helicobacter Infections/genetics* ; Helicobacter pylori ; Lymphatic Metastasis ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Polycomb Repressive Complex 1/genetics*