Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Guided by the concept of holism in traditional Chinese medicine （TCM）， it is believed that spinal vertebral disorders can affect the knee joint through meridians， physical forms， the relationship among tendons， bones， qi， and blood， as well as liver-kidney zang-fu （脏腑） functions， thereby triggering knee pain. In clinical practice， for conditions such as knee joint pain with poor local therapeutic effects or unexplained knee joint pain， it is recommended to start with an examination of the spine for lesions. By adopting the spine-adjusting and knee-benefiting method， through techniques of loosening and tightening acupoints， bone setting and curve adjustment， strengthening tendons and bones， and consolidating and protecting the liver and kidneys， the spine can be restored to its normal physiological state， achieving the goal of distal tendon-bone balance， harmonization of qi and blood， and the spontaneous disappearance of knee joint pain.

ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC₅₀ value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.