1.Treatment of Hyperuricemia and Gouty Arthritis by Buyang Huanwu Tongfeng Decoction via Inhibition of PPAR-γ/NF-κB/AGEs/RAGE Pathway Based on Network Pharmacology
Yue CAO ; Wanmei YAO ; Tao YANG ; Man YANG ; Ruimin JIA ; Rongrong LU ; Xue FENG ; Biwang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):182-192
ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology(GO) enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software, and the protein-protein interaction (PPI) network for key targets was depicted. Finally, the hub gene was determined through topological analysis. Auto Dock, PyMOL, and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments, a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin(HE) staining, uric acid test, enzyme linked immunosorbent assay(ELISA), Western blot, and real-time polymerase chain reaction(Real-time PCR), the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values, 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response, astrocyte activation, regulation of interleukin (IL)-8 production, nuclear receptor activity, and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway, advanced glycosylation end/receptor of advanced glycation endproducts(AGE/RAGE) signaling pathway, anti-inflammatory, and other pathways. PPI network indicated that albumin(ALB), peroxisome proliferator-activated receptor-γ (PPAR-γ), IL-6, IL-1β, and C-reactive protein(CRP) were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene (β-carotene). Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose (7.76 g·kg-1·d-1), medium-dose (15.53 g·kg-1·d-1), and high-dose (31.05 g·kg-1·d-1) groups of Buyang Huanwu Tongfeng decoction had different degrees of remission, and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration, as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced, followed by the medium-dose and low-dose groups, and the expression of ALB, PPAR-γ, IL-6, IL-1β, and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB, PPAR-γ, IL-6, IL-1β, and CRP, inhibiting the PPAR-γ/nuclear transcription factor (NF)-κB pathway, and reducing AGEs/RAGE-mediated inflammation, Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.
2.Concept, design and clinical application of minimally invasive liver transplantation through laparoscopic combined upper midline incision
Shuhong YI ; Hui TANG ; Kaining ZENG ; Xiao FENG ; Binsheng FU ; Qing YANG ; Jia YAO ; Yang YANG ; Guihua CHEN
Organ Transplantation 2025;16(1):67-73
Objective To explore the technical process and clinical application of laparoscopic combined upper midline incision minimally invasive liver transplantation. Methods A retrospective analysis was conducted on 30 cases of laparoscopic combined upper midline incision minimally invasive liver transplantation. The cases were divided into cirrhosis group (15 cases) and liver failure group (15 cases) based on the primary disease. The surgical and postoperative conditions of the two groups were compared. Results All patients successfully underwent laparoscopic "clockwise" liver resection, with no cases of passive conversion to open surgery or intolerance to pneumoperitoneum. In 6 cases, the right lobe was relatively large, and the right hepatic ligaments could not be completely mobilized. One case required an additional reverse "L" incision during open surgery. All patients successfully completed the liver transplantation, with no major intraoperative bleeding, cardiovascular events, or other occurrences in the 30 patients. The model for end-stage liver disease (MELD) score in the cirrhosis group was lower than that in the liver failure group (P<0.001). There were no statistically significant differences between the two groups in terms of age, surgical time, blood loss, anhepatic phase, or cold ischemia time (all P>0.05). During the perioperative period, there was 1 case of hepatic artery embolism, 1 case of portal vein anastomotic stenosis, no complications of hepatic vein and inferior vena cava, and 3 cases of biliary anastomotic stenosis, all of which occurred in the liver failure group. Conclusions In strictly selected cases, the minimally invasive liver transplantation technique combining laparoscopic hepatectomy with upper midline incision for graft implantation has the advantages of smaller incisions, less bleeding, relatively easier operation, and faster postoperative recovery, which is worthy of clinical promotion and application.
3.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
4.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides
Lin-Fang CHEN ; Jia-Fan ZHANG ; Ye-Ning GUO ; Hui-Zhong HUANG ; Kang-Hong HU ; Chen-Guang YAO
Progress in Biochemistry and Biophysics 2025;52(1):50-60
Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.
5.Interpretation of 2024 ESC guidelines for the management of elevated blood pressure and hypertension
Yu CHENG ; Yiheng ZHOU ; Yao LÜ ; ; Dongze LI ; Lidi LIU ; Peng ZHANG ; Rong YANG ; Yu JIA ; Rui ZENG ; Zhi WAN ; Xiaoyang LIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):31-40
The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."
6.Isoliquiritigenin alleviates abnormal endoplasmic reticulum stress induced by type 2 diabetes mellitus
Kai-yi LAI ; Wen-wen DING ; Jia-yu ZHANG ; Xiao-xue YANG ; Wen-bo GAO ; Yao XIAO ; Ying LIU
Acta Pharmaceutica Sinica 2025;60(1):130-140
Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms.
7.Statistical considerations in the design of albumin clinical trials
Yuanyuan KONG ; Chen YAO ; Jidong JIA
Journal of Clinical Hepatology 2025;41(3):420-423
Albumin is widely used in clinical practice, and the rationality of trial design directly affects the reliability of research findings and clinical application value. This article reviews the key statistical considerations in the design of albumin clinical trials, including the selection of primary endpoints, the establishment of statistical hypotheses and non-inferiority margins, clinical evaluation criteria for ascites improvement, sample size, and interim analyses, in order to provide methodological guidance for clinical researchers to optimize clinical trial design and enhance its scientific rigor and feasibility.
8.Geographical Inference Study of Dust Samples From Four Cities in China Based on ITS2 Sequencing
Wen-Jun ZHANG ; Yao-Sen FENG ; Jia-Jin PENG ; Kai FENG ; Ye DENG ; Ke-Lai KANG ; Le WANG
Progress in Biochemistry and Biophysics 2025;52(4):970-981
ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.
9.Value of third lumbar skeletal muscle mass index in predicting the prognosis of patients with acute-on-chronic liver failure
Yewen HAN ; Jing LI ; Ninghui ZHAO ; Jia YAO ; Juan WANG
Journal of Clinical Hepatology 2025;41(4):698-702
ObjectiveTo investigate the value of third lumbar skeletal muscle mass index (L3-SMI) in predicting the long-term prognosis of patients with acute-on-chronic liver failure (ACLF), and to provide a useful tool for prognostic scoring of ACLF patients. MethodsA retrospective analysis was performed for the data of 126 patients who underwent abdominal computed tomography (CT) scanning and were diagnosed with ACLF in Shanxi Bethune Hospital from December 2017 to December 2021, including clinical indicators, biochemical parameters, and model for end-stage liver disease (MELD) score, and L3-SMI was calculated. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of L3-SMI and other variables (MELD score and Child-Pugh score), and the DeLong test was used for comparison of the area under the ROC curve (AUC). ResultsAmong the 126 patients enrolled, 44 (35%) died within 2 years and 82 (65%) survived. Compared with the survival group, the death group had significantly higher age, incidence rate of ascites, international normalized ratio, MELD score, and Child-Pugh score (all P<0.05) and a significantly lower value of L3-SMI [38.40 (35.95 — 46.29) cm²/m² vs 44.19 (40.20 — 48.58) cm²/m², Z=-2.855, P=0.004]. L3-SMI had an AUC of 0.720 in predicting 2-year mortality in ACLF patients, with a sensitivity of 63.6% and a specificity of 80.5%, and a combination of L3-SMI, MELD score, and Child-Pugh score had a significantly better AUC than a combination of MELD score and Child-Pugh score in predicting 2-year mortality (0.809 vs 0.757, Z=2.015, P<0.05). ConclusionL3-SMI has a high predictive value for the prognosis of ACLF patients, and the combination of L3-SMI、MELD score and Child-Pugh score has a higher predictive value for ACLF patients, and the inclusion of L3-SMI or sarcopenia in the conventional prognostic scores of ACLF patients may increase the ability to predict disease progression.
10.Application of middle hepatic vein splitting and reconstruction technique in split liver transplantation from low-age donor livers
Hui TANG ; Binsheng FU ; Qing YANG ; Jia YAO ; Kaining ZENG ; Xiao FENG ; Shuhong YI ; Yang YANG
Organ Transplantation 2025;16(3):453-459
Objective To explore the feasibility and clinical experience of the middle hepatic vein splitting-reconstruction technique in split liver transplantation from low-age donor livers. Methods A retrospective analysis was conducted on the cases of two low-age donor livers that underwent middle hepatic vein splitting-reconstruction, which were transplanted into four child recipients at the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to July 2023. The surgical and postoperative conditions were summarized and analyzed. Results Donor 1 was a 6-year-old and 4-month-old girl with a body weight of 21 kg, and the obtained donor liver weighed 496 g. After splitting, the left and right liver weights were 201 g and 280 g, and transplanted into a 9-month-old boy weighing 6.5 kg and a 9-month-old boy weighing 7.5 kg, respectively. The graft to recipient weight ratio (GRWR) was 3.09% and 3.73%, respectively. Donor 2 was a 5-year-old and 8-month-old boy with a body weight of 19 kg, and the donor liver weighed 673 g. After splitting, the left and right liver weights were 230 g and 400 g, and transplanted into a 13-month-old girl weighing 9.5 kg and a 15-month-old boy weighing 12 kg. The GRWR was 2.42% and 3.33%, respectively. Both donor livers were split ex vivo, with the middle hepatic vein being completely split in the middle and reconstructed using allogeneic iliac vein and iliac artery vascular patches. According to GRWR, none of the 4 transplant livers were reduced in volume. Among the 4 recipients, one died due to postoperative portal vein thrombosis and non-function of the transplant liver, while the other three cases recovered smoothly without early or late complications. Regular follow-up was conducted until July 31, 2023, and liver function recovered well. Conclusions Under the premise of detailed assessment of the donor liver and meticulous intraoperative operation, as well as matching with suitable child recipients, low-age donor livers may be selected for splitting. The complete splitting and reconstruction of the middle hepatic vein in the middle may effectively ensure the adequate venous return of the left and right liver and provide sufficient functional liver volume.

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