Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

OBJECTIVES: To investigate the effect of Ching Shum Pills (CSP) for alleviating non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism. METHODS: In a mouse model of NAFLD, the therapeutic effect of CSP was evaluated by measuring serum glucose, lipid profiles (TC, TG, LDL-C, HDL-C), and hepatic function markers. Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP, HERB, SwissTargetPrediction, GeneCards, OMIM, and DisGeNET. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway analyses were conducted. Molecular docking (AutoDock Vina) was used to assess the compound-target binding affinities. Quantitative real-time PCR (qRT-PCR) was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models. RESULTS: In the mouse model of NAFLD, treatment with CSP significantly reduced body weight gain and serum TG levels of the mice, and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation. Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP, which target TNF, AKT1, IL6, TP53, and ALB. Docking simulations suggested strong binding between the two core compounds and their target proteins. The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53, Cpt1, and Ppara expressions in mice, which was effectively reversed by CSP treatment. CONCLUSIONS CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function. The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Lipid Metabolism/drug effects* ; Molecular Docking Simulation ; Disease Models, Animal ; Liver/metabolism* ; Male ; Lipid Metabolism Disorders/drug therapy* ; PPAR alpha/metabolism* ; Mice, Inbred C57BL ; Network Pharmacology

Hypoxic injury (HI) in the prenatal period often causes neonatal neurological disabilities. Due to the difficulty in obtaining clinical samples, the molecular and cellular mechanisms remain unclear. Here we use vascularized cerebral organoids to investigate the hypoxic injury phenotype and explore the intercellular interactions between vascular and neural tissues under hypoxic conditions. Our results indicate that fused vascularized cerebral organoids exhibit broader hypoxic responses and larger decreases in panels of neural development-related genes when exposed to low oxygen levels compared to single cerebral organoids. Interestingly, vessels also exhibit neural protective effects on T-box brain protein 2⁺ intermediate progenitors (IPs), which are markedly lost in HI cerebral organoids. Furthermore, we identify the role of bone morphogenic protein signaling in protecting IPs. Thus, this study has established an in vitro organoid system that can be used to study the contribution of vessels to brain injury under hypoxic conditions and provides a strategy for the identification of intervention targets.
Organoids/pathology* ; Animals ; Mice ; Hypoxia, Brain/metabolism* ; Brain/blood supply* ; Neurons/metabolism*

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Ethanol detection plays an important role in food industry,environmental monitoring,medical health monitoring,prevention of drunk driving,etc.The development of low-cost,high-performance ethanol sensors has important application value.In this study,a ZnO/FeS nano heterojunction ethanol sensor was prepared on commercial ceramic silver electrode substrate.The sensing characteristics of the sensor for ethanol gas were systematically studied.The results showed that ZnO had a nanowire structure,and the FeS was coated on the ZnO nanowire in the form of nanosheets.The sensor performed well for ethanol detection in environments with relative humidity ranging from 30%to 60%,with a detection range from 0.2 mg/m3 to 50 mg/m3.At the optimum operating temperature of 300℃,the response of ZnO/FeS nano heterojunction sensor to 50 mg/m3 ethanol was 15.6,the response time was 5.0 s,and the detection limit was as low as 0.101 mg/m3,which was obviously better than that of commercial ethanol sensor.This sensor was highly selective for ethanol compared to other gases such as CO,NH3,acetone,etc,and could steadily work for 30 days.The fabricated sensor had good development potential in the field of low-cost and high-performance ethanol gas detection.

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.

Objective To investigate the effect of Ching Shum Pills(CSP)for alleviating non-alcoholic fatty liver disease(NAFLD)and the underlying mechanism.Methods In a mouse model of NAFLD,the therapeutic effect of CSP was evaluated by measuring serum glucose,lipid profiles(TC,TG,LDL-C,HDL-C),and hepatic function markers.Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP,HERB,SwissTargetPrediction,GeneCards,OMIM,and DisGeNET.Protein-protein interaction(PPI)networks,Gene Ontology(GO),and KEGG pathway analyses were conducted.Molecular docking(AutoDock Vina)was used to assess the compound-target binding affinities.Quantitative real-time PCR(qRT-PCR)was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models.Results In the mouse model of NAFLD,treatment with CSP significantly reduced body weight gain and serum TG levels of the mice,and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation.Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP,which target TNF,AKT1,IL6,TP53,and ALB.Docking simulations suggested strong binding between the two core compounds and their target proteins.The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53,Cpt1,and Ppara expressions in mice,which was effectively reversed by CSP treatment.Conclusion CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function.The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.