Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

With the continuous development of experimental biology, the limitations of commonly utilized model organisms are becoming increasingly apparent. Discrepancies between research conducted on laboratory animals and humans significantly impede the translational application of findings derived from animal experiments. This review introduces ascidian Ciona intestinalis as a novel model organism, an invertebrate that is evolutionarily closest to vertebrates and is a sister group to vertebrates. The review summarizes recent research progress on Ciona intestinalis in various fields to illustrate the significant advantages and promising application prospects of it as a model organism. The research progress outlined in the review mainly encompasses: (1) The whole-genome sequencing of Ciona intestinalis has been determined and numerous related databases have been established. Various embryonic gene editing technologies have been successfully applied, making it an animal model easy to manipulate genetically and study the functions and interactions of target genes visually. (2) In the field of neurobiology, Ciona intestinalis boasts a central nervous system structure similar to that of vertebrates and possesses numerous homologous neuropeptides and hormone molecules. These features grant it an edge in exploring the mechanisms and functional evolution of endocrine and neuroendocrine-related molecules. Additionally, the sensitivity and habituation of its larvae to light stimulation provide an avenue for exploring mechanisms related to behavioral plasticity. (3) In the field of immunology, Ciona intestinalis possesses a mature innate immune system and has evolved precursor genes to the adaptive immune system, with a relatively simple coding of immune-related genes. These features make it an exemplary model organism for immunological studies. (4) In the field of developmental biology, many studies have focused on the notochord development process in Ciona intestinalis and the regulatory mechanisms of gene expression within it, indicating common evolutionary developmental strategies among chordates. Additionally, insights into its heart development also significantly enhance our comprehension on the genetic network of human heart development. (5) In medical research, the ability of Ciona intestinalis to regenerate its neural complex and siphon, as well as the resilience of its heart to recover contractile function from substantial damage, renders it a valuable animal model for the study of regeneration and heart injury. It also has unique advantages as a research model for Alzheimer's disease and new drug development. Furthermore, its brief five-month lifespan facilitates the observation and recording of the entire aging process and the exploration of the effects of various factors on aging. In summary, this review aims to demonstrate that Ciona intestinalis stands out as a model organism with unique attributes and is expected to play a significant role in a wider range of scientific research areas.

【Objective】 To explore the causal relationship between education level and pancreatitis risk through Mendelian randomization. 【Methods】 A two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) summary data. The GWAS data for education level and pancreatitis were obtained from SSGAC database and the FinnGen database (version R9). Causal relationship between education level and pancreatitis was explored using the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Heterogeneity and directional pleiotropy were evaluated using Cochran’s Q test and funnel plots. 【Results】 Totally 604 SNPs associated with education level were included. The results provided evidence that there was negative relationship between education level and pancreatitis risk. For acute pancreatitis, OR=0.52, 95% CI: 0.44-0.62, P=2.43×10^-14 while for chronic pancreatitis, OR=0.51, 95% CI: 0.41-0.64, P=7.20×10^-9. Results from MR-Egger and weighted median analyses obtained the same results. The results of sensitivity analysis indicated that this study did not violate the basic assumptions of Mendelian randomization. 【Conclusion】 There is a causal relationship between education level and the occurrence of pancreatitis. The educational level is negatively correlated with the risk of pancreatitis.

Objective:To carry out a scoping review on the development process, main forms, main contents and outcome indicators of decision aids for thyroid cancer patients, providing a theoretical basis for future research in China.Methods:The Arksey and O'Malley's methodological framework was used to analyze the literature. Electronic retrieval was conducted in PubMed, Cochrane Library, Embase, Web of Science, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Database, and the search period was from database establishment to August 21, 2023.Results:A total of 11 articles were included. The forms of decision aids included paper decision support manuals, web-based decision support tools, conversation support tools and so on. The main content was to provide disease knowledge and the advantages and disadvantages of various treatment plans, help patients clarify their values, understand patient preferences, and assist doctors and patients make decisions. Outcome indicators involved treatment choice, medical knowledge, decision conflict, decision regret, decision satisfaction, anxiety and so on.Conclusions:The application of decision aids has a positive effect in thyroid cancer patients. Future research should encourage many people to participate in decision-making in order to improve the quality of decision-making for thyroid cancer patients.

Objective To construct and validate an effective prognostic nomogram for the patients with incidental gallbladder cancer(IGBC).Methods The clinical data of 161 patients with IGBC requiring radical surgery admitted to the First Affiliated Hospital of Xi'an Jiaotong University from May 2011 to October 2022 was analyzed retrospectively.COX proportional risk regression model was used to screen for influencing factors on overall survival(OS)of IGBC.Nomogram was constructed based on independent influencing factors that affected the prognosis of IGBC patients.The concordance index(C-index)and calibration curve were used to validate the performance of the model.Receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA)were used to validate the predictive accuracy and net benefit of the plotted column chart.Results Univariate COX regression analysis suggested that age,T stage,N stage,M stage,preoperative carcinoembryonic antigen(CEA),preoperative carbohydrate antigenl9-9(CA19-9),preoperative red blood cell volume distribution on width coefficient of variation(RDW-CV),treatment method,and recurrence and metastasis were risk factors which affected the long-term survival of IGBC patients after radical surgery.Multivariate COX regression analysis suggested that T stage,N stage,preoperative CA19-9,preoperative RDW-CV,preoperative AST,treatment methods,and recurrence and metastasis were independent risk factors which affected the prognosis of IGBC patients.The C-index of the constructed prognostic model was 0.872.The calibration plot demonstrated good performance of the Nomogram.ROC curve analysis showed an area under the curve of 0.869,confirming a high sensitivity and specificity.A high net benefit was proven by DCA.Conclusions The constructed Nomogram.can accurately and intuitively predict the survival probability of IGBC patients after radical surgery.

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
Rats ; Animals ; Doxorubicin/adverse effects* ; Nephrotic Syndrome ; AMP-Activated Protein Kinases/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

Epiphyseal plate injury in children is very common, which can be caused by fracture, infection, malignant tumors, iatrogenic injury or other causes.Growth arrest and angulation or rotation deformity after epiphyseal plate injury would seriously affect the physical and mental health of children.At present, the success rate of bone bridge resection combined with corresponding material filling is super low.The construction of bioactive epiphyseal cartilage using cartilage tissue engineering technology has become a new research direction for the treatment of epiphyseal plate injury in children.Therefore, this review focuses on the current research on the regeneration of epiphyseal cartilage from the perspective of 3 elements of tissue engineering: seed cells, growth factors, and tissue engineering scaffolds.

Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.

Objective:To study the characteristics of the lens turbidity after long-term exposure to low intensity 635nm laser.Methods:Cluster sampling method was adopted to select 812 employees in a laser leveler workshop in a city of Guangdong Province from January 2014 to December 2018. They were divided into the control group, diffuse reflection (DR) group and direct vision (DV) group for retrospective observation and analysis of lens turbidity. The laser irradiation intensity of each group was investigated, the position and shape of lens opacity were analyzed, and the influencing factors were statistically analyzed with the repeated measurement data of dichotomy.Results:The laser irradiance and radiant exposure of DV group were between 0.72×10 -4 and 9.92×10 -4 mW/cm 2 and between 2.61×10 -2 and 1.53 J/cm 2, respectively. The subjects were mainly diagnosed with lens turbidity lesion, especially for the DV group. Most of lesions occurred in the pole and periphery of the anterior cortex. The lesions exhibited multipoint patterns with greyish white color. The turbidity rates in DV group (before work and work for 1, 2, 3 years) were 0%, 1.99% (8/402) , 4.98% (20/402) and 6.72% (27/402) , respectively, in the order of observation points. The statistical analysis of single factor effect showed that the turbidity rate was higher in DV group and higher in the second year in the DV group ( P<0.01) . Multi-factor analysis of the laser effect on the lens showed that the main effect between groups, between the observation point were statistically significant ( P<0.05) , but no statistical significance in the interaction between group×observation points ( P>0.05) . Conclusion:Lens turbidity lesion can be caused by long-term exposure to low intensity 635 nm laser, so the product safety classification should be strictly strengthened. It is necessary to strengthen the protection of laser photochemical damage in the production process.

Objective:To study the characteristics of the lens turbidity after long-term exposure to low intensity 635nm laser.Methods:Cluster sampling method was adopted to select 812 employees in a laser leveler workshop in a city of Guangdong Province from January 2014 to December 2018. They were divided into the control group, diffuse reflection (DR) group and direct vision (DV) group for retrospective observation and analysis of lens turbidity. The laser irradiation intensity of each group was investigated, the position and shape of lens opacity were analyzed, and the influencing factors were statistically analyzed with the repeated measurement data of dichotomy.Results:The laser irradiance and radiant exposure of DV group were between 0.72×10 -4 and 9.92×10 -4 mW/cm 2 and between 2.61×10 -2 and 1.53 J/cm 2, respectively. The subjects were mainly diagnosed with lens turbidity lesion, especially for the DV group. Most of lesions occurred in the pole and periphery of the anterior cortex. The lesions exhibited multipoint patterns with greyish white color. The turbidity rates in DV group (before work and work for 1, 2, 3 years) were 0%, 1.99% (8/402) , 4.98% (20/402) and 6.72% (27/402) , respectively, in the order of observation points. The statistical analysis of single factor effect showed that the turbidity rate was higher in DV group and higher in the second year in the DV group ( P<0.01) . Multi-factor analysis of the laser effect on the lens showed that the main effect between groups, between the observation point were statistically significant ( P<0.05) , but no statistical significance in the interaction between group×observation points ( P>0.05) . Conclusion:Lens turbidity lesion can be caused by long-term exposure to low intensity 635 nm laser, so the product safety classification should be strictly strengthened. It is necessary to strengthen the protection of laser photochemical damage in the production process.