OBJECTIVE:Disorders in iron metabolism increase the risk of type 2 diabetes mellitus.Hepcidin play an important role in maintaining iron homeostasis in the body,but its level increases with increased inflammation.Changes in hepcidin and iron homeostasis and the extent of their association with inflammation in people with and without type 2 diabetes mellitus are unknown.Meta-analysis was used to evaluate the effect of inflammation on serum hepcidin and iron metabolism related parameters in patients with type 2 diabetes mellitus.METHODS:CNKI,PubMed,Web of Science and EBSCOhost databases were searched by computer to collect observational studies related to inflammatory index and hepcidin in patients with type 2 diabetes mellitus.The search time was from September 1,2000 to September 30,2024.Three researchers independently screened the literature,extracted data and evaluated the quality of the included literature.Meta-analysis was performed by Review Manager 5.3,Stata 17.0 and GraphPad Prism 8.0.2 software.RESULTS:A total of 15 articles(17 studies)involving 3 159 participants,including 1 357 patients with type 2 diabetes mellitus,were included.Meta-analysis results showed that compared with the control group,patients with type 2 diabetes mellitus had higher levels of serum hepcidin[standardized mean difference(SMD)=0.35,95％confidence interval(CI)(0.05,0.65),P＜0.05],serum ferritin(SMD=0.49,95％CI(0.21,0.78),P＜0.01)and serum transferrin(SMD=0.19,95％CI(0.00,0.37),P＜0.05).Subgroup analysis results indicated that inflammation had a significant effect on serum hepcidin(SMD=0.76,95％CI(0.17,1.34),P＜0.05)and serum ferritin(SMD=0.77,95％CI(0.06,1.47),P＜0.05)in patients with type 2 diabetes mellitus.CONCLUSION:Hepcidin concentration is positively correlated with type 2 diabetes mellitus.Inflammation is one of the risk factors of type 2 diabetes mellitus.Early prevention of inflammation has certain significance in preventing iron metabolism disorder in patients with type 2 diabetes mellitus.

ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.

OBJECTIVE:Disorders in iron metabolism increase the risk of type 2 diabetes mellitus.Hepcidin play an important role in maintaining iron homeostasis in the body,but its level increases with increased inflammation.Changes in hepcidin and iron homeostasis and the extent of their association with inflammation in people with and without type 2 diabetes mellitus are unknown.Meta-analysis was used to evaluate the effect of inflammation on serum hepcidin and iron metabolism related parameters in patients with type 2 diabetes mellitus.METHODS:CNKI,PubMed,Web of Science and EBSCOhost databases were searched by computer to collect observational studies related to inflammatory index and hepcidin in patients with type 2 diabetes mellitus.The search time was from September 1,2000 to September 30,2024.Three researchers independently screened the literature,extracted data and evaluated the quality of the included literature.Meta-analysis was performed by Review Manager 5.3,Stata 17.0 and GraphPad Prism 8.0.2 software.RESULTS:A total of 15 articles(17 studies)involving 3 159 participants,including 1 357 patients with type 2 diabetes mellitus,were included.Meta-analysis results showed that compared with the control group,patients with type 2 diabetes mellitus had higher levels of serum hepcidin[standardized mean difference(SMD)=0.35,95％confidence interval(CI)(0.05,0.65),P＜0.05],serum ferritin(SMD=0.49,95％CI(0.21,0.78),P＜0.01)and serum transferrin(SMD=0.19,95％CI(0.00,0.37),P＜0.05).Subgroup analysis results indicated that inflammation had a significant effect on serum hepcidin(SMD=0.76,95％CI(0.17,1.34),P＜0.05)and serum ferritin(SMD=0.77,95％CI(0.06,1.47),P＜0.05)in patients with type 2 diabetes mellitus.CONCLUSION:Hepcidin concentration is positively correlated with type 2 diabetes mellitus.Inflammation is one of the risk factors of type 2 diabetes mellitus.Early prevention of inflammation has certain significance in preventing iron metabolism disorder in patients with type 2 diabetes mellitus.

ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride （CCl₄） and olive oil. One hundred and four SD rats were randomized into thirteen groups：a normal group，a two-week model group，a four-week model group，a six-week model group，an eight-week model group，a two-week Qijia Rougan formula group，a four-week Qijia Rougan formula group，a six-week Qijia Rougan formula group，an eight-week Qijia Rougan formula group，a two-week compound Biejia Ruangan tablet group，a four-week Compound Biejia Ruangan Tablet group，a six-week Compound Biejia Ruangan Tablet group，and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention，liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin （HE） staining，Masson staining，and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry （IHC） was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer，and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay （ELISA）. Liver tissues from the normal group，each model group，and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups，with key proteins validated by Western blot. Finally，bioinformatics analysis was performed on the differential proteins. Results（1） The staged rat model of liver fibrosis constructed with CCl₄ and olive oil showed pathological results at the 2^nd，4^th，6^th，and 8^th weeks of modeling that were consistent with the Metavir standards for the F1，F2，F3，and F4 stages. Compared with those in the normal control group，the protein expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were significantly increased in each stage （P<0.05）. The levels of liver function indicators in the serum，including alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），direct bilirubin （DBIL），and total bilirubin （TBil） in each model group，were significantly elevated in each stage （P<0.01）. The levels of liver fibrosis indicators in the serum，including procollagen Ⅲ peptide （PⅢP），type Ⅳ collagen（Ⅳ-C），hyaluronic acid （HA），and laminin （LN） in each model group，were significantly increased in each stage （P<0.05，P<0.01）. This study successfully established a staged rat model of liver fibrosis. （2） Compared with the model groups at each stage，the administration groups showed a reduction in hepatocyte ballooning degeneration，a more orderly arrangement of hepatocytes，and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer，with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced （P<0.05）. The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased （P<0.05）. The levels of ALT，AST，ALP，DBIL，and TBil in the rats of the model groups at each stage were significantly reduced （P<0.05，P<0.01）. The levels of PⅢP，Ⅳ-C，HA，and LN in the rats of the model groups at each stage were significantly decreased （P<0.05）. Among these，the improvements in all indicators were most significant in the F3 stage （P<0.01）.（3） The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group，and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD（P）H：quinone oxidoreductase 1 （NQO1），mitogen-activated protein kinase 1 （MAPK1），arginase 1 （Arg1），and glutathione S-transferase α1 （GSTA1） were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably，signaling pathways such as drug metabolism-cytochrome P450，arginine biosynthesis，and the peroxisome proliferator-activated receptor （PPAR） signaling pathway were found to be closely associated with liver fibrosis，suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450，arginine biosynthesis，and the PPAR signaling pathway.

ObjectiveTo investigate the association of the traditional Chinese medicine （TCM） syndrome types of primary liver cancer （PLC） with clinical features and multimodal quantitative radiological features on computed tomography （CT） and magnetic resonance imaging （MRI）， and to provide a reference for the objectification of TCM syndrome differentiation and precise diagnosis and treatment. MethodsA retrospective analysis was performed for the clinical data of 312 patients who were diagnosed with PLC in The First Affiliated Hospital of Hunan University of Chinese Medicine from March 2020 to June 2025， and according to the TCM syndrome type， they were divided into stagnation of liver Qi group with 40 patients， stagnation of liver Qi and spleen deficiency group with 109 patients， Qi stagnation and blood stasis group with 62 patients， dampness-heat toxin amassment group with 81 patients， and liver-kidney Yin deficiency group with 20 patients. Clinical features and multimodal quantitative radiological features were compared between the patients with different TCM syndrome types. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s multiple test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups， and the Bonferroni method was used for further comparison between two groups. ResultsThere were significant differences between the patients with different TCM syndrome types in China liver cancer staging （CNLC）， Child-Pugh class， alanine aminotransferase， aspartate aminotransferase， albumin， direct bilirubin， total bilirubin， prothrombin time， neutrophil， and albumin-bilirubin score （all P<0.05）. In the stagnation of liver Qi group， the patients with Child-Pugh class A accounted for 75.00%； among the patients with CNLC stage I PLC， the patients with stagnation of liver Qi accounted for 60.00%， and those with Qi stagnation and blood stasis syndrome accounted for 59.68%， while among the patients with CNLC stage IV PLC， the distribution proportion of dampness-heat toxin amassment （27.16%） and liver-kidney Yin deficiency （30.00%） was significantly higher than that of stagnation of liver Qi （2.50%） （all P<0.05）. Radiological examination showed that there were significant differences between the patients with different TCM syndrome types in the number of tumors， ascites， venous tumor thrombus， maximum tumor diameter， intrahepatic metastasis， and lymph node metastasis in the hepatic hilar and retroperitoneal regions （all P<0.05）. Compared with the patients with stagnation of liver Qi， the patients with liver depression and spleen deficiency or liver-kidney Yin deficiency were more likely to develop intrahepatic metastasis； the patients with liver depression and spleen deficiency， dampness-heat toxin amassment， or liver-kidney Yin deficiency were more likely to develop lymph node metastasis in the hepatic hilar and retroperitoneal regions； the patients with liver-kidney Yin deficiency were more likely to experience multiple tumors； the patients with liver depression and spleen deficiency or dampness-heat toxin amassment were more likely to develop ascites （all P<0.05）. Compared with the patients with Qi stagnation and blood stasis syndrome， the patients with liver depression and spleen deficiency had a significantly longer maximum tumor diameter and a significantly higher proportion of patients with venous tumor thrombus （both P<0.05）. Furthermore， among the 184 patients with MRI diffusion-weighted imaging sequences， the patients with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome had significantly higher ADC values and relative ADC values than those with stagnation of liver Qi （all P<0.05）. ConclusionThere are significant differences in CT/MRI radiological features and clinical features between PLC patients with different TCM syndrome types， among whom the patients with liver depression and spleen deficiency， dampness-heat toxin amassment， and liver-kidney Yin deficiency tend to exhibit progressive radiological features， and those with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome tend to have higher ADC values. These findings provide an objective basis for TCM syndrome differentiation in PLC.

Objective To investigate the factors influencing the persistence of residual low back pain following percutaneous vertebroplasty(PVP)in patients with osteoporotic vertebral fractures(OVF),in order to provide a scientific basis for clinical intervention strategies.Methods A retrospective analysis was conducted on data from 1 120 patients diagnosed with OVF who received PVP treatment between July 2020 and June 2025.Among them,61 patients who experienced residual low back pain in the early postoperative period(defined as 2 days to 1 month after surgery)with a postoperative visual analog scale(VAS)score greater than 3 points were selected as the observation group.An additional 61 control subjects were matched to the observation group at a 1∶1 ratio based on age(±5 years),gender,and preoperative bone mineral density(±0.5 standard deviation).Univariate and logistic regression analyses were subsequently performed to evaluate potential influencing factors.Results Univariate analysis revealed statistically significant differences between the two groups with respect to preoperative thoracolumbar fascia injury(TFI),MRI-detected liquefaction signals in the affected vertebrae,the number of involved vertebrae(≥2),and suboptimal bone cement distribution(P<0.05).Multivariate regression analysis confirmed that these factors were independent risk factors,with corresponding odds ratios(ORs)of 5.378,6.111,3.245,and 2.890(all P<0.05).The area under the curve(AUC)of the predictive model was 0.929,indicating a high level of predictive accuracy.Conclusion Preoperative TFI,MRI-demonstrated liquefaction signals in the affected vertebrae,the presence of multiple responsible vertebrae,and suboptimal bone cement distribution may contribute to an increased risk of early residual low back pain following PVP.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.