Objective To investigate the inhibitory effect of Zheng Gan Decoction(ZGF)on tumor progression in a rat model of diethylnitrosamine(DEN)-induced hepatocellular carcinoma(HCC)and explore the possible mechanism.Methods Seventy SD rats were subjected to regular intraperitoneal injections of DEN(50 mg/kg)for 12 weeks to induce HCC tumorigenesis,with another 10 rats receiving saline injections as the normal control.After successful modeling,the rats were randomized into 5 groups(n=10)for daily treatment with distilled water(model group),Huaier Granules(4 g/kg;positive control group),or ZGF at low,medium,and high doses(2,4,and 8 g/kg,respectively)via gavage for 17 weeks.Body weight changes of the rats were monitored,and after completion of the treatments,the rats were euthanized for measurement of liver,spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining.The expressions of YAP,p-YAP,MST1,LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting.Results Compared with the normal control rats,the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate,increased body weight and liver and spleen indices,and a lowered thymus index.ZGF treatment obviously reduced liver and spleen indices,increased the thymus index,and improved pathologies of the liver tissues of the rat models.Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats,which also exhibited significantly upregulated hepatic expressions of MST1,LATS1 and p-LATS1.Conclusion ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression,which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals, including humans (Montoya and Liesenfeld, 2004). It occurs worldwide and can persist for a lifetime in mammals. Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite. In immune-competent individuals, T. gondii infection usually does not cause significant clinical symptoms, whereas in pregnant or immunocompromised individuals, T. gondii infection (toxoplasmosis) can cause more serious problems like abortion and even death (Dunn et al., 1999; Wang et al., 2017). A combination of pyrimethamine and sulfadiazine is usually used to treat toxoplasmosis, although it is generally inefficient and causes side effects (Alday and Doggett, 2017). Worse still, there is a lack of vaccines to prevent T. gondii infection in humans or animals.
Toxoplasma/enzymology* ; Animals ; Humans ; Toxoplasmosis ; Mitochondria/enzymology* ; Protozoan Proteins/metabolism*

OBJECTIVES: To investigate the inhibitory effect of Zheng GanDecoction (ZGF) on tumor progression in a rat model of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and explore the possible mechanism. METHODS: Seventy SD rats were subjected to regular intraperitoneal injections of DEN (50 mg/kg) for 12 weeks to induce HCC tumorigenesis, with another 10 rats receiving saline injections as the normal control. After successful modeling, the rats were randomized into 5 groups (n=10) for daily treatment with distilled water ( model group), Huaier Granules (4 g/kg; positive control group), or ZGF at low, medium, and high doses (2, 4, and 8 g/kg, respectively) via gavage for 17 weeks. Body weight changes of the rats were monitored, and after completion of the treatments, the rats were euthanized for measurement of liver, spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining. The expressions of YAP, p-YAP, MST1, LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting. RESULTS: Compared with the normal control rats, the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate, increased body weight and liver and spleen indices, and a lowered thymus index. ZGF treatment obviously reduced liver and spleen indices, increased the thymus index, and improved pathologies of the liver tissues of the rat models. Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats, which also exhibited significantly upregulated hepatic expressions of MST1, LATS1 and p-LATS1. CONCLUSIONS ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression, which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Diethylnitrosamine ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Protein Serine-Threonine Kinases/metabolism* ; Carcinoma, Hepatocellular/drug therapy* ; YAP-Signaling Proteins ; Liver Neoplasms/drug therapy* ; Hippo Signaling Pathway ; Male ; Liver Neoplasms, Experimental/metabolism* ; Transcription Factors/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

Objectives:To evaluate the biomechanics of a new self-developed bidirectional self-locking fusion device in vitro.Methods:12 fresh L3/4 segment specimens of domestic pig spine were randomly divided into 3 groups for modeling:normal group(intact state),traditional fusion device group(traditional fusion device and unilateral screw fixation)and new fusion device group(bidirectional self-locking fusion device implanted).On the basis of MTS multi-freedom(spinal motion)simulation test system and 500N preload,8N·m load was applied to experimental specimens in each direction successively,and the stability test was carried out according to the order of forward bending,backward extension,left bending,right bending,and left and right rotation.The ranges of motion(ROMs)were compared between groups under different working conditions.The axial fatigue compression test was carried out with TT-JQ-01-106 fatigue testing machine to evaluate the stability and reliability of the self-developed fusion device.Results:Compared with the normal group,the ROM of the new fusion device group was significantly decreased under the conditions of flexion(1.67°±0.65° vs 3.46°±0.16°),extension(1.43°±1.01° vs 1.89°±0.29°),left bending(2.07°±1.32° vs 3.08°±0.09°),right bending(1.38°±0.72° vs 4.37°±0.20°),and right rotation(2.17°±1.51° vs 5.10°±0.37°)(all P＜0.05);Under the left rotation condition,the ROM value(3.10°±1.57°)of the new device group was significantly higher than that of the normal group(2.36°±0.62°)(P＜0.05).Compared with the conventional fusion device group,the ROM of the new fusion device group was significantly increased under flexion(1.67°±0.65° vs 1.22°±0.76°)and left rotation(3.10°±1.57° vs 1.57°±0.91°)conditions(P＜0.05);However,there were no significant differences in ROMs between the two groups under extension(1.43°±1.01° vs 1.06°±0.50°),left bending(2.07°±1.32° vs 1.87°±1.41°),right bending(1.38°±0.72° vs 1.45°±0.69°),and right rotation(2.17°±1.51° vs 1.69°±1.07°)conditions(P＞0.05).The ROM values of the normal group under flexion,extension,left bending,right bending,and right rotation conditions were significantly higher than those of the other two groups(P＜0.05).Fatigue test:after 5 million load-displacement cycles,visual inspection revealed no deformation or cracks in the fusion device,and the axial compression fatigue test was passed.Conclusions:The bidirectional self-locking fusion device can obviously improve the stability of the fusion segment,which is equivalent to the stability of using the posterior single-sided nail rod system,meanwhile,it has good fatigue resistance,therefore its mechanical properties can meet the needs of clinical applications.

Objectives:To evaluate the biomechanics of a new self-developed bidirectional self-locking fusion device in vitro.Methods:12 fresh L3/4 segment specimens of domestic pig spine were randomly divided into 3 groups for modeling:normal group(intact state),traditional fusion device group(traditional fusion device and unilateral screw fixation)and new fusion device group(bidirectional self-locking fusion device implanted).On the basis of MTS multi-freedom(spinal motion)simulation test system and 500N preload,8N·m load was applied to experimental specimens in each direction successively,and the stability test was carried out according to the order of forward bending,backward extension,left bending,right bending,and left and right rotation.The ranges of motion(ROMs)were compared between groups under different working conditions.The axial fatigue compression test was carried out with TT-JQ-01-106 fatigue testing machine to evaluate the stability and reliability of the self-developed fusion device.Results:Compared with the normal group,the ROM of the new fusion device group was significantly decreased under the conditions of flexion(1.67°±0.65° vs 3.46°±0.16°),extension(1.43°±1.01° vs 1.89°±0.29°),left bending(2.07°±1.32° vs 3.08°±0.09°),right bending(1.38°±0.72° vs 4.37°±0.20°),and right rotation(2.17°±1.51° vs 5.10°±0.37°)(all P＜0.05);Under the left rotation condition,the ROM value(3.10°±1.57°)of the new device group was significantly higher than that of the normal group(2.36°±0.62°)(P＜0.05).Compared with the conventional fusion device group,the ROM of the new fusion device group was significantly increased under flexion(1.67°±0.65° vs 1.22°±0.76°)and left rotation(3.10°±1.57° vs 1.57°±0.91°)conditions(P＜0.05);However,there were no significant differences in ROMs between the two groups under extension(1.43°±1.01° vs 1.06°±0.50°),left bending(2.07°±1.32° vs 1.87°±1.41°),right bending(1.38°±0.72° vs 1.45°±0.69°),and right rotation(2.17°±1.51° vs 1.69°±1.07°)conditions(P＞0.05).The ROM values of the normal group under flexion,extension,left bending,right bending,and right rotation conditions were significantly higher than those of the other two groups(P＜0.05).Fatigue test:after 5 million load-displacement cycles,visual inspection revealed no deformation or cracks in the fusion device,and the axial compression fatigue test was passed.Conclusions:The bidirectional self-locking fusion device can obviously improve the stability of the fusion segment,which is equivalent to the stability of using the posterior single-sided nail rod system,meanwhile,it has good fatigue resistance,therefore its mechanical properties can meet the needs of clinical applications.

Huangqitang comes from the Taiping Huimin Hejiju Fang of the Song dynasty. It consists of four medicinal materials: Astragalus membranaceus var. mongholicus, Citrμs reticμlata， Cannabis sativa， and Apis cerana. It is a classic prescription for treating constipation in the elderly. This study systematically collated the literature records about Huangqitang in ancient Chinese medicine books and combined it with the current status of modern clinical applications to conduct in-depth analysis and research on the origin，composition， dosage, processing, preparation and administration, drug base, main symptoms， and other key information of the formula, so as to provide a strong reference for the development and clinical application of the classic Huangqitang compound preparation. Through systematic combing and textual research on the previous literature of Huangqitang， it can be seen that the formula of Huangqitang was first recorded in the Taiping Huimin Hejiju Fang， and the medical books of the past dynasties mostly adopted this formula. In terms of drug base， the dried roots of the leguminous plant Astragalus membranaceus var. mongholicus are used， and for tangerine， the dried outer peel of the Rutaceae plant Citrus reticμlata and its cultivated varieties are used. The Moraceae plant Cannabis sativa with the peel removed is selected, and the Apis cerana is selected from the honey brewed by Apis cerana， an insect of the Apidae family. In terms of dosage， although the dosage of some drugs changed during the Ming and Qing dynasties, the dosage records basically followed the original prescriptions from the Song dynasty. In terms of processing, preparation, and usage， although the drug processing， preparation， and usage of Huangqitang in the medical books of the past dynasties have changed slightly， they are basically the same as the original prescription of the Song dynasty. In terms of main symptoms, Huangqitang is designed to treat constipation in the elderly. From the Song dynasty to the Qing dynasty， it was mostly used to treat constipation， secret congestion, asthenia， etc. in the elderly. In modern times， it is clinically used to treat constipation due to Qi deficiency， functional constipation， irritable bowel syndrome， and other diseases in the elderly. No adverse reactions have been found yet. In the subsequent research and development， it is necessary to carry out mass spectrometry analysis of Huangqitang， in-depth exploration of its prescription efficacy and mechanism of action， and other multi-omics scientific research. At the same time， it is important to establish quality control standards to provide a reliable scientific basis for the research and development, clinical treatment， and drug supervision of Huangqitang compound preparations.

Asian ginseng mostly appeared in herbal medical books in the late Qing Dynasty and the early Republic of China.In modern literature,it is believed that this drug is alias of vigorously cultivated ginseng,Talinum paniculatum(Jacq.)Gaertn.,Pananis Japonici Rhizoma,Arctii Fructus and other drugs,and the origin is confused.This article made a textual research on the name,origin,producing areas,processing,property and taste,and efficacy.It is concluded that the Asian ginseng was earlier included in the Ben Cao Gang Mu Shi Yi in the Qing Dynasty,and was named Asian ginseng because it was produced in Japan.The original plant is Panax ginseng C.A.Meyer,which is a kind of Araliaceae plant.It takes Yunzhou,Huijin and Xinzhou of Japan as the true land,and is also cultivated in Northeast China.Asian ginseng medicinal materials are made by processing techniques such as net whiskers,boiling,cooling,and exposure to dryness.They are warm in property,sweet and slightly bitter in taste.They are good at tonifying qi and generating fluid,and can treat all deficiency syndromes of fluid and qi.In the Qing Dynasty,they were often used as Ginseng Radix et Rhizoma.The identification of false was also attached for distinguishing.

Objective·To elucidate the regulatory mechanisms of the chromobox protein homolog 8(CBX8)in prostate cancer metastasis from transcriptome and epigenetic modification perspectives.Methods·The correlation between the expression of CBX proteins and prostate adenocarcinoma(PRAD)in The Cancer Genome Atlas(TCGA)was examined through an analysis based on cBioPortal database.A stable CBX8 knockdown DU 145 prostate cancer cell line was established via short hairpin RNA(shRNA)transfection.Subsequently,the proliferation and invasion of the CBX8 knockdown cells were analyzed by CCK-8 assay and Transwell assay,respectively.Transcriptome changes of the CBX8 knockdown cells were investigated through RNA sequencing(RNA-seq)coupled with Gene Set Enrichment Analysis(GSEA).To further evaluate the functional implications of these transcriptomic alterations,Gene Ontology(GO)for functional analysis was deployed.Moreover,to identify potentially affected signalling pathways,the Kyoto Encyclopedia of Genes and Genomes(KEGG)was utilized for pathway enrichment analysis.Lastly,the levels of H3K27me3,a key histone modification associated with CBX8,in the knockdown cells were determined by chromatin immunoprecipitation sequencing(ChIP-seq).Results·Bioinformatic analysis with cBioPortal database,based on TCGA-PRAD cohorts,unveiled a high CBX8 mRNA expression in PRAD.Knockdown of CBX8 did not significantly affect the proliferation of DU 145 cells(P＞0.05),but caused a a significant increase in their invasiveness(P＜0.05).The RNA-seq analysis revealed that CBX8 knockdown led to the upregulation of 750 genes and the downregulation of 951 genes.Notably,branched-chain-amino-acid aminotransferase 1(BCAT1),a gene implicated in the metastasis of various types of cancers,showed a significant increase in expression following CBX8 knockdown.GSEA showed that the expression levels were of the affected genes were related to the functions of the polycomb repressive complex 1(PRC1).A further investigation using GO and KEGG analyses identified several enriched pathways in the CBX8 knockdown cells,including transfer RNA(tRNA)aminoacylation,DNA replication,changes in aminoacyl-tRNA ligase activity,and cadherin binding.Interestingly,in terms of cell component of GO functional analysis,cell-substrate junction-related genes associated with tumor metastasis appeared to be enriched.ChIP-seq results showed a global decrease in H3K27me3 levels.Significantly,97 reduced H3K27me3 peaks were found located nearby genes that were upregulated upon CBX8 knockdown,including the transcriptional start site of BCAT1.Conclusion·CBX8 is highly expressed in prostate cancer.CBX8 suppresses prostate cancer cell invasion,possibly by recruiting the transcriptional repressive PRC1 complex to the transcription site of BCAT1,thereby inhibiting BCAT1 transcription and tumor metastasis.