Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

OBJECTIVE To explore a multimodal analgesia regimen based on spinal cord electrical stimulation for children with primary erythromelalgia and the key points of pharmaceutical care. METHODS Clinical pharmacists participated in the treatment of a child with primary erythromelalgia complicated with skin infection. After reviewing domestic and foreign literature， multimodal analgesia was formulated and pharmaceutical care was carried out to address the difficulties in treating the patient’s illness. RESULTS The treatment team applied multimodal analgesia based on spinal cord electrical stimulation for the child， including a multi-drug combination involving different analgesic pharmacological targets， multiple administration routes （oral， intravenous， epidural， percutaneous）， multiple technologies （spinal cord electrical stimulation， local nerve block， patient- controlled analgesia）， individualized schemes of adjuvant therapy， and the child was monitored for the safety of drug use. The pain was controlled during the treatment and follow-up period， the wound was healed， and no serious adverse drug reactions occurred. CONCLUSIONS Multimodal analgesia based on spinal cord electrical stimulation is a safe and effective treatment for children with primary erythromelalgia.

Objective To optimize the oxygen therapy regimens for infants with pulmonary diseases during bronchoscopy.Methods A prospective randomized,controlled,and single-center clinical trial was conducted on 42 infants who underwent electronic bronchoscopy from July 2019 to July 2021.These infants were divided into a nasal cannula(NC)group and a modified T-piece resuscitator(TPR)group using a random number table.The lowest intraoperative blood oxygen saturation was recorded as the primary outcome,and intraoperative heart rate and respiratory results were recorded as the secondary outcomes.Results Compared with the NC group,the modified TPR group had a significantly higher level of minimum oxygen saturation during surgery and a significantly lower incidence rate of hypoxemia(P<0.05).In the modified TPR group,there were 6 infants with mild hypoxemia,2 with moderate hypoxemia,and 1 with severe hypoxemia,while in the NC group,there were 3 infants with mild hypoxemia,5 with moderate hypoxemia,and 9 with severe hypoxemia(P<0.05).The modified TPR group had a significantly lower incidence rate of intraoperative respiratory rhythm abnormalities than the NC group(P<0.05),but there was no significant difference in the incidence rate of arrhythmias between the two groups(P>0.05).Conclusions Modified TPR can significantly reduce the risk of hypoxemia in infants with pulmonary diseases during electronic bronchoscopy,and TPR significantly decreases the severity of hypoxemia and the incidence of respiratory rhythm abnormalities compared with traditional NC.

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of the right elbow reveals in a "semi-extended and pronated" elastic fixation position. Radiography and 3-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Objective:To screen the aging genes closely associated with pelvic organ prolapse(POP)by bioinformatics techniques,and to clarify the potential clinical significance and value of key genes.Methods:Gene Expression Omnibus(GEO)Database was used to download the datasets GSE53868 and GSE151188 for POP-related genes with the keyword"pelvic organ prolapse".The aging-related genes were obtained from Aging Atlas,CellAge,and the Human Ageing Genomic Resources(HAGR)Databases;the intersection of genes related with POP in two groups provided a list of differentially expressed genes(DEGs)associated with aging in POP;gene Set Enrichment Analysis(GSEA)was conducted with R software version 4.2.1;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis of DEGs were conducted by the Database for Annotation,Visualization and Integrated Discovery(DAVID);the protein-protein interaction(PPI)network was constructed with Cytoscape 3.9.1 software;the top 10 Hub genes were selected by cytoHubba plugin;the infiltration of 22 types of immune cells in the patients in POP group and control group was analyzed by CIBERSORT deconvolution method using R software;the key genes were further screened by LASSO regression algorithm;the correlation and diagnostic efficacy between key genes and immune cell infiltration were analyzed.Results:From the Aging Atlas,CellAge,and HAGR Databases,724 aging-related genes were identified.Intersection with the POP expression profile yielded an aging gene expression matrix related to POP containing 624 genes,and 29 POP-related DEGs were identified after differential analysis,including 2 upregulated genes and 27 downregulated genes.The GSEA results showed that the upregulated pathways were mainly related to diabetes and cellular senescence,whereas the downregulated pathways included Alzheimer's disease and hypoxia-inducible factor-1(HIF-1)signaling pathways.The GO functional enrichment analysis mainly enriched in the biological processes such as the response of the cells to lipopolysaccharide,inflammatory response,and negative regulation of cell proliferation.The KEGG signaling pathway enrichment analysis mainly enriched in interleukin-17(IL-17),tumor necrosis factor(TNF),and nuclear factor-kappa B(NF-κB)signaling pathways.The PPI network analysis got 10 Hub genes including interleukin-6(IL-6),interleukin-1B(IL-1B),prostaglandin-endoperoxide synthase 2(PTGS2),and NF-kappa-B inhibitor alpha(NFKBIA).The CIBERSORT deconvolution method results showed a relatively higher infiltration proportion of neutrophils and activated mast cells in the patients in POP group,the activated mast cells had a positive correlation with most of the DEGs(r>0.5)and the macrophages had a significant positive correlation with IL-1B(r>0.6).The key genes Jun D proto-oncogene(JUND),Snail homolog 1(SNAI1),amphiregulin(AREG),Lamin A/C(LMNA),and superoxide dismutase 2(SOD2)selected by LASSO regression analysis had high diagnostic efficacies,and the area under receiver operating characteristic curve(ROC)(AUC)were all greater than 0.75.Conclusion:During the aging process,the genes such as JUND,SNAI1,AREG,LMNA,and SOD2 may participate in the pathophysiology of POP through various pathways,including inflammation-related pathways,transcription regulation,and affecting collagen secretion and metabolism,thereby influence the connective tissue support function and promote the occurrence and development of POP.

Relative to hepatitis B virus(HBV)monoinfection,HBV/hepatitis D virus(HDV)co-infection may be associated with more severe liver disease,leading to increased rates of cirrhosis,hepatocellular carcinoma,hepatic decompensation,and liver failure.The treatment of chronic HDV infection is essential and urgent.No drugs with established Efficacy and safety data have been approved for the treatment of chronic HDV infection.There are several new drugs are in clinical development stage now.We review the mechanism of action,research and development progress,and clinical trial design of new drugs currently in the clinical development stage,as well as the recommendations of regulatory agencies and academia for the clinical trial design of new drugs for the treatment of chronic HDV infection.And discuss the key points of confirmatory clinical trial design.

AIM:This study aimed to investigate the mechanism by which celoside I enhances mitophagy in a model of optic nerve injury through regulation of reactive oxygen species(ROS)-mediated c-Jun N-terminal kinase(JNK)/c-Jun signaling pathway.METHODS:Twenty-four New Zealand white rabbits were randomly divided into four groups:sham surgery,model,mecobalamin,and experimental group.Optic nerve injury was induced in the model,mecobala-min,and experimental groups,while the sham surgery group underwent a sham procedure.The mecobalamin group re-ceived mecobalamin,the experimental group received celoside I,and the sham surgery and model groups received saline.Interventions were administered daily for 28 d.Various techniques including endoscopy,hematoxylin-eosin(HE)stain-ing,TUNEL method,immunofluorescence staining and Western blot were used to assess fundus condition,retinal mor-phology,apoptosis,ROS expression,and protein levels in the retina.RESULTS:Fundus examination revealed im-proved blood flow in the mecobalamin and experimental groups compared to the model group.Retinal morphology showed enhanced retinal ganglion cells(RGCs)in the mecobalamin and experimental groups.Apoptosis index was lower in the mecobalamin group compared to the experimental group.Immunofluorescence staining indicated reduced ROS and P62 ex-pression and increased parkin and microtubule-associated protein light chain 3(LC3)expression in the experimental group compared to the mecobalamin group.Protein analysis showed decreased JNK,c-Jun,and P62 levels,and increased parkin and LC3 levels in the mecobalamin and experimental groups compared to the model group.CONCLUSION:Celo-side I reduces ROS expression,inhibits the JNK/c-Jun pathway,enhances mitophagy,reduces apoptosis,and protects RGCs in optic nerve injury models.

Objective:To discover the relationship between the RNF213 gene and acute myeloid leukemia(AML),and explore the effect of RNF213 on the proliferation and apoptosis of THP-1 cells.Methods:Analyze the expression of RNF213 gene in AML and its relationship with prognosis through the GEPIA database.Collecting 30 AML patients and non-tumor hematological patients who went to the Affiliated Hospital of Zunyi Medical University from January 2017 to January 2022.RT-qPCR and Western blot were used to detect the expression levels of RNF213 mRNA and protein.Perform survival of patients was analysed by Kaplan-Meier.Meanwhile,the expression levels of RNF213 mRNA and protein were detected in AML cell lines(THP-1,OCI-AML2).CRISPR-Cas9 was used to knockdown the RNF213 gene in THP-1 cells;flow cytometry was used to detect apoptosis rate of cell.CCK-8 and colony formation assay were used to detect cell proliferation.Western blot was used to detect the expression level of Cleaved-Caspase 3 protein.Results:Compared with the control group,the expression level of RNF213 in AML patients was significantly increased,and patients with high expression of RNF213 have a worse prgnosis.Higher expression level of RNF213 protein in THP-1 cells.After knocking down the RNF213 gene of THP-1 cells,cell proliferation was significantly reduced,and the apoptosis rate and expression of apoptosis related protein Cleared-Caspase3 were significantly increased.Conclusion:AML patients have high expression of RNF213,and the prognosis of high expression patients is poor.The RNF213 gene affects AML cell proliferation and apoptosis,and may be a prognostic marker and potential therapeutic target for AML.