BACKGROUND: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.

Objective To establish a prognostic nomogram based on preoperative serum prealbumin levels for predicting overall survival(OS)in patients with unresectable hepatocellular carcinoma(HCC)treated with transcatheter arterial chemoembolization(TACE).Methods A total of 1 041 patients with unresectable HCC,who received TACE treatment at five medical centers in Suzhou city of China between January 2007 and December 2018,were divided into a training cohort(n=768)and a validation cohort(n=273).Cox regression analysis was used to analyzed the independent factors affecting one-,2-,and 3-year OS,based on which the nomogram was constructed,and validation of the nomogram was conducted in an internal test sequence.The performance of the nomogram was evaluated by concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curve,and judgment curve analysis(DCA).Results COX regression analysis showed that AFP,BCLC,HBV,intrahepatic vascular invasion,number of tumors,PALB,PS,and tumor size were the independent risk factors affecting OS in patients with unresectable HCC treated with TACE.The C-index in the nomogram was 0.739(95％CI:0.719-0.759)for the training cohort and 0.715(95％CI:0.678-0.752)for the verification cohort.The AUCs of one-,2-,and 3-year OS in the training cohort were 0.877,0.794,and 0.799 respectively,which in the verification cohort were 0.840,0.741,and 0.671 respectively.The AUC-ROC values of the nomogram were higher than those of other traditional scoring systems,indicating that the nomogram had a good discriminatory power.The calibration curves demonstrated that a strong agreement existed between the predicted values of the nomogram and the actual observed values,and the DCA showed that the nomogram had high potential clinical utilization.The nomogram risk score revealed that the survival rate of patients in the low-risk group was significantly higher than that of patients in the high-risk group.Conclusion The nomogram based on preoperative serum prealbumin levels has excellent ability in predicting the prognosis of patients with unresectable HCC treated with TACE.

Objective To construct and validate a predictive model based on preoperative inflammatory biomarkers,and to evaluate its ability in predicting the prognosis of patients with unresectable hepatocellular carcinoma(HCC)after receiving transcatheter arterial chemoembolization(TACE).Methods A total of 544 patients with HCC,who received TACE as the initial treatment at six medical institutions between January 2007 and December 2020,were retrospectively collected.The patients were divided into training cohort(n=376)and validation cohort(n=168).LASSO algorithm and Cox regression analysis were used to screen out the independent influencing factors and to make modelling.The model was validated based on the discrimination,calibration and clinical applicability,and the Kaplan-Meier risk stratification curves were plotted to determine the prognostic differences between groups.The likelihood ratio chi-square value,R2 value,akaike information criterion(AIC)value,C-index and AUROC value of the model were calculated to determine its accuracy and efficiency.Results The training cohort and validation cohort had 376 participants and 168 participants respectively.Multivariate analysis indicated that BCLC,tumor size,number of tumor lesions,neutrophil and prognostic nutritional index(PNI)were the independent influencing factors for postoperative overall survival(OS),with all P being＜0.05;the BCLC grade,tumor size,number of tumor lesions,NLR,PNI and PS score were the independent influencing factors for progression-free survival(PFS),with all P being＜0.05.The C-indexes of the OS and PFS models were 0.735(95％ CI=0.708-0.762)and 0.736(95％ CI=0.711-0.761)respectively,and the external validation was 0.721(95％ CI=0.680-0.762)and 0.693(95％ CI=0.656-0.730)respectively.Ideal discrimination ability of the nomogram was exhibited in time-dependent C-index,time-dependent ROC,and time-dependent AUC.The calibration curves significantly coincided with the ideal standard lines,indicating that the model had high stability and low over-fitting level.Decision curve analysis revealed that there was a wider range of threshold probabilities and it could augment net benefits.The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically between risk categories(P＜0.000 1).The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically among different risk groups(P＜0.000 1).The likelihood ratio chi-square value,R2 value,AIC value,C-index and AUROC value of the model were better than those of other models commonly used in clinical practice.Conclusion The newly-developed prognostic nomogram based on preoperative inflammatory indicators has excellent accuracy as well as excellent prediction effect in predicting the prognosis of patients with unresectable HCC after receiving TACE,therefore,it can be used as an effective tool for guiding individualized treatment and for predicting prognosis.(J Intervent Radiol,2024,33:245-258)

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

A 14-year-old boy presented with coma and convulsion following a 3-day high fever of unknown origin was initially diagnosed with a central nervous system infection with uncertain pathogen. Direct microscopic examination of wet slides of cerebrospinal fluid cytology revealed active amoeboid trophozoites with different shapes. The amoeba trophozoite could be seen at high magnification after Wright′s-Giemsa staining. A diagnosis of primary amoebic meningoencephalitis was made according to the cellular morphology results of the cerebrospinal fluid, imaging data, and clinical symptoms. After high-throughput gene detection targeting the infection pathogen and specific PCR verification of amoeba species, it was confirmed that the infection was caused by Naegleria fowleri. Timely antiamoebic treatment and other related treatments were implemented, but the patient progressed to brain death after 50 days, leading to the discontinuation of treatment by the family.

Objective:To investigate the effects of preoperative mammalian target of rapamycin(mTOR )inhibitor on partial nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML).Methods:A retrospective analysis was conducted on clinical data from 13 patients who were diagnosed with TSC-RAML and treated at Peking Union Medical College Hospital between August 2019 and July 2022. This cohort included 4 males and 9 females, with ages ranging from 22 to 66 years. All patients underwent partial nephrectomy, with 2 patients requiring two-stage surgeries due to bilateral RAMLs, resulting in a total of 15 surgeries being performed. Preoperative mTOR inhibitors, specifically everolimus (10 mg/d) or sirolimus (2 mg/d), were administered orally for at least 3 months prior to 7 of the surgeries. The effects of mTOR inhibitors on tumor size, tumor computed tomography attenuation value (CT value), and tumor CT enhancement were evaluated. The comparison of surgery-related clinical parameters was conducted between patients who received preoperative mTOR inhibitors and those who did not to assess the influences of mTOR inhibitors on surgery.Results:Compared to the baseline tumor, there was a significant reduction in tumor diameter after mTOR treatment [(6.4±3.1) cm vs. (8.7±3.9)cm], as well as in the CT value in both the unenhanced phase[(-18.63±48.73)HU vs. (-2.13±51.58)HU] and corticomedullary phase[(13.25±64.01)HU vs. (47.25±66.99)HU]. Additionally, tumor CT enhancement also decreased as compared with that before treatment [(31.88±18.20)HU vs. (49.38±20.63)HU]. Patients who received preoperative mTOR inhibitor showed a trend towards shorter operative time for removing per milliliter of tumor compared to those without preoperative mTOR inhibitor [1.06(0.18, 2.40) min/ml vs. 1.98(0.39, 5.03) min/ml] and so was the renal artery clamping time [0.17(0.03, 0.79) min/ml vs. 0.34(0.10, 1.71) min/ml]. Additionally, the amount of intraoperative bleeding for removing per milliliter of tumor was lower in patients with preoperative mTOR inhibitors compared to those without [0.72(0.19, 0.88) ml/ml vs. 1.69(0.59, 4.54) ml/ml].Conclusions:The administration of mTOR inhibitors before partial nephrectomy in patients with TSC-RAM have the potential to reduce tumor size and blood supply, as well as operative time, renal artery clamping time and intraoperative bleeding, which might contribute to surgery safety and preservation of renal function.

Objective:To analyze and explore the possible mechanism of anti-tumor metastasis of Notoginseng Radix et Rhizoma using Internet pharmacology. Methods:The active components and targets of Notoginseng Radix et Rhizoma were screened by retrieving Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). GeneCards database was used to screen the anti-tumor metastasis-related targets, and compounds and disease targets were under mapping analysis. Key targets of Notoginseng Radix et Rhizoma for anti-tumor metastasis were screened through Venn map. With the help of Cytoscape 3.7.2 software, a compound-disease network diagram was constructed. String platform was used to build a PPI network. Bioconductor was used to enrich the target genes for KEGG signaling pathway and GO biological process analysis. Results:Totally 119 active components were selected from Notoginseng Radix et Rhizoma. There were 8 eligible active components, corresponding to 162 related targets, 121 targets related to anti-tumor metastasis, and 30 key targets screened by PPI network, including AKT1, MAPK1, JUN, RELA, IL6, etc. GO enrichment analysis mainly involved biological processes such as cytokine receptor binding, heme binding, RNA polymerase Ⅱ transcription factor binding, ubiquitin protein ligase binding, and steroid hormone receptor activity. 149 signal pathways related to Notoginseng Radix et Rhizoma anti-tumor metastasis were obtained by KEGG enrichment analysis, mainly involving multiple signal pathways, such as AGE-RAGE and PI3K-Akt, and hepatitis B, Kaposi's sarcoma-associated herpes virus infection, human cytomegalovirus infection and other viral infections and various tumors. Conclusion:Notoginseng Radix et Rhizoma can pass multiple active components, such as ginsenoside f2, ginsenoside rh2 β-, sitosterol, stigmasterol and quercetin, and multiple targets, such as AKT1, MAPK1, JUN, RELA and IL6, acting on multiple pathways such as PI3K-Akt, thereby playing the role of anti-tumor metastasis.

Objective:To review relevant research on the application of self-help intervention model in adult depression patients, analyze the main characteristics and application effects of self-help intervention model, in order to provide reference for related research in this field.Methods:According to the methodological framework of the scope review, searched 12 Chinese and English databases including CNKI, Wanfang, PubMed, Web of Science, etc. from the establishment of the database until April 20, 2021, and sorted and analyzed the obtained documents according to the inclusion and exclusion standards.Results:A total of 45 documents were included, of which only 5 were from China; the included studies were mainly based on the Internet platform, using cognitive behavioral therapy, reading therapy, acceptance and commitment therapy, and problem-solving therapy for intervention; the duration of the intervention was 3 weeks to 4 months, participants complete an intervention module or read a specified number of chapters every 3 to 7 days on average, and receive regular guidance and supervision from the intervention facilitator every 1-2 weeks. The total contact time with the facilitator was 80-160 minutes. Various modes of self-help intervention based on the Internet could effectively improve the negative emotions of patients with depression.Conclusions:The self-help intervention model has shown good results in the treatment of patients with depression, but there is a lack of local intervention research in China, and there is no clear standard for the number of interventions and the length of the intervention guide. Under the general trend of "Internet + medical health", it is necessary to actively construct a self-help intervention model for depression with Chinese cultural characteristics, and form a systematic and standardized intervention strategy to address the many obstacles in time, location, resources and cost of people with depression, and finally achieve the purpose of improving the patients′ depressive symptoms and helping them to restore their social functions.

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.
Animals ; Cell Line, Tumor ; Cell Proliferation ; Follicle Stimulating Hormone/metabolism* ; Gene Expression Regulation, Neoplastic ; In Situ Hybridization, Fluorescence ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Rats