Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage， and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation， and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora， short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways， thereby playing an important role in the diagnosis， treatment， and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs， this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE， in order to provide new ideas for optimizing clinical prevention and treatment strategies.

Macroporous resin adsorption column chromatography, silica gel column chromatography, ODS column chromatography, and semi-preparative high-performance liquid chromatography, combined with analytical methods such as NMR and MS, were employed to separate and identify compounds from the 70% ethanol extract of Ajania purpurea. A total of 30 compounds were isolated and identified, including 13 phenolic acids, 7 coumarins, 2 lignans, 1 flavonoid, 2 sesquiterpenes, 1 steroid, and 4 others. Among them, compounds 1 and 2 were newly discovered compounds, and compounds 4, 6, 8, 12, 14-23, 25, 28, and 30 were isolated from Ajania plants for the first time. Bioactivity screening showed that multiple compounds significantly inhibited the production of nitric oxide in lipopolysaccharide-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, compound 2 elevated the levels of glutathione in LPS-induced BEAS-2B cells, reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β, enhanced the mRNA of GPX4, HMOX1, NFE2L2, and enhanced protein levels of GPX4, HO-1, Nrf2, and SLC7A11, demonstrating potential anti-ferroptotic effect.
Mice ; Animals ; Lignans/isolation & purification* ; RAW 264.7 Cells ; Humans ; Nitric Oxide ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; NF-E2-Related Factor 2/metabolism* ; Macrophages/metabolism* ; Interleukin-6/immunology*

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

OBJECTIVE To explore the distribution pattern of traditional Chinese medicine(TCM)syndrome types of primary o-varian insufficiency(POI)sleep disorders and the differences in the distribution of sleep quality index among different syndrome types,in order to provide a basis for syndrome differentiation treatment and prevention of POI associated with sleep disorders.METHODS 600 POI patients who met the inclusion criteria were collected for epidemiological investigation,and 405 patients who met the diagnosis of sleep disorders were selected as the research group.The patients'general information,TCM four diagnosis and sex hormone level in-formation were collected,and the Pittsburgh sleep quality index(PSQI)scale was used to evaluate patients'sleep conditions,and ana-lyze the characteristics and influencing factors of TCM syndrome types of POI associated with sleep disorders.RESULTS The main TCM syndrome types of POI accompanied by sleep disorders were heart and kidney disharmony syndrome(41.98%),spleen and kid-ney yang deficiency syndrome(22.22%),kidney deficiency and liver stagnation syndrome(20.99%),and kidney deficiency and blood stasis syndrome(14.81%).The heart and kidney disharmony syndrome had the longest sleep latency and shortest sleep time,relied more on hypnotic drugs,and had the highest PSQI total score;the heart and kidney disharmony syndrome and kidney deficiency and liver stagnation syndrome had the worst sleep quality;the spleen kidney yang deficiency syndrome had the highest daytime dysfunc-tion score.There was no significant difference in FSH levels among different TCM syndrome types;the distribution of E2 values from low to high was:heart and kidney disharmony syndrome,kidney deficiency and liver stagnation syndrome,spleen and kidney yang de-ficiency syndrome,and kidney deficiency and blood stasis syndrome,and there were significant differences among multiple groups(P<0.05).CONCLUSION The main TCM syndrome types of patients with POI and sleep disorders are heart and kidney disharmony syn-drome,spleen and kidney yang deficiency syndrome,kidney deficiency and liver stagnation syndrome,and kidney deficiency and blood stasis syndrome.Among them,the most common TCM syndrome type with the worst sleep quality is heart and kidney disharmony syn-drome,which may be closely related to estrogen E2 levels.

In recent years,with the gradual maturity of achievable remote collection of digital health technology,more and more clinical research have applied this technology to improve the quality of data collection and reduce the burden on subjects.However,its technological characteristics of detachment from the diagnostic and treatment environment and real-time transmission of sensitive information also pose corresponding risks to the protection of subjects'rights and interests and data standardization management,among which personal information protection and data control permissions are more prominent issues.Based on risk analysis and regulatory review,this paper explored the responsibilities of multiple parties,including the sponsors,researchers,clinical trial institutions,and ethics committee,as well as proposed five elements of special concern for ethical review,with a view to providing a reference for promoting the standardized development of digital health technology in clinical research.

Osteoarthropathy is a common chronic disease among middle-aged and elderly populations, characterized by joint pain, limited mobility, and even disability in severe cases. Treatment methods include weight control, functional exercise, local or systemic medication use, and ultimately joint replacement surgery. However, patients often experience ineffective drug treatment or inability to tolerate adverse drug reactions, as well as inability to tolerate joint replacement surgery. Multiple studies have shown that low-dose radiotherapy can alleviate joint pain and limited mobility by regulating multiple stages of the inflammatory process. In addition, the risk of secondary malignant tumors is extremely low, with rare acute and chronic adverse reactions. However, there is still some controversy regarding the optimal segmentation method for radiotherapy in clinical applications, which remains to be elucidated by more prospective studies. Low-dose radiotherapy for osteoarthropathy has been rarely studied in China. This non-invasive, safe, and effective treatment is expected to provide more treatment options for Chinese patients with osteoarthritis.