ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

Objective:To evaluate the efficacy of gadolinium ethoxybenzyl- diethy-lenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI features in the preoperative prediction of tertiary lymphoid structures (TLS) within hepatocellular carcinoma (HCC) lesions.Methods:This retrospective cross-sectional study included clinical and pathological data from 297 HCC patients treated at the Southwest Hospital, Army Medical University between June 2021 and November 2022. Based on postoperative pathology, patients were categorized into TLS-negative ( n=93) and TLS-positive ( n=204) groups. MRI features of HCC lesions using Gd-EOB-DTPA enhancement and relevant clinical data were analyzed. Intergroup comparisons of imaging features and laboratory findings were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The logistic regression analysis was conducted to identify independent predictors of TLS positivity. A predictive model was constructed and visualized using a nomogram. The model′s predictive performance and clinical utility were assessed using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) was compared using the DeLong test. Results:Significant differences were observed between the TLS-negative and TLS-positive groups in alpha-fetoprotein (AFP) levels, intratumoral hemorrhage, and peritumoral satellite nodules in the hepatobiliary phase ( P<0.05). Multivariate logistic regression identified intratumoral hemorrhage ( OR=0.123, 95% CI 0.070-0.216, P<0.001) and peritumoral satellite nodules in the hepatobiliary phase ( OR=0.236, 95% CI 0.093-0.596, P=0.002) as independent predictive factors for TLS-positivity. The imaging model based on these two features yielded an AUC of 0.764 (95% CI 0.709-0.809) for predicting TLS-positivity. When combined with AFP levels, the resulting clinical-imaging model achieved a superior AUC of 0.784 (95% CI 0.732-0.829), which was significantly higher than that of the imaging model alone ( Z=2.20, P=0.028). A nomogram was constructed based on the clinical-imaging model. The calibration curve demonstrated good predictive performance of the nomogram, and the DCA showed that the curve remained above the default line across a range of reasonable threshold probabilities, indicating that patients could derive clinical benefit. Conclusion:A nomogram model based on Gd-EOB-DTPA enhanced MRI features combined with AFP levels can effectively predict the presence of TLS in HCC.

Objective To investigate the mechanism of action and potential biomarkers of Jiangzhi Qingshen capsules in the treatment of dyslipidaemia based on clinical lipid metabolomics.Methods 30 patients with dyslipidaemia from Zhengzhou Hospital of Chinese Medicine were collected as the test group,and their lipid levels before and after taking Jiang Zhi Qing Shen capsule for 12 weeks were compared.Another 30 healthy patients were enrolled in the physical examination department of Zhengzhou Hospital of Chinese Medicine,and metabolomics investigation was carried out on plasma samples of the test group before and after the treatment as well as those of the healthy patients by LC-MS/MS technology.The differences between the groups were compared by multivariate statistical analysis,and the potential biomarkers were identified by HMDB and lipidblast databases,so as to clarify the possible pathways and targets for the treatment of mild dyslipidaemia by Jiangzhi Qingshen capsules.Results Jiangzhi Qingshen capsules could improve patients' blood lipid level,BMI and abdominal circumference significantly(P<0.05).And metabolomics results showed that 29 lipid metabolites in the plasma of the treated patients were dialled back,which involved cholesterol metabolism,fat digestion and absorption,glycerol-phospholipid metabolism and other biological processes.Conclusion The efficacy of Jiangzhi Qingshen capsules in treating dyslipidaemia was confirmed,and its mechanism of action might be related to the regulation of lipid metabolism.Metabolites such as acylcarnitine(Acar),phosphatidylethanolamine(PE)and phosphatidylcholine(PC)were expected to be used as the biomarkers of dyslipidaemia,so as to provide objective scientific basis for the lipid-lowering capsule,and to facilitate the promotion of its application.

Objective To investigate the mechanism of action and potential biomarkers of Jiangzhi Qingshen capsules in the treatment of dyslipidaemia based on clinical lipid metabolomics.Methods 30 patients with dyslipidaemia from Zhengzhou Hospital of Chinese Medicine were collected as the test group,and their lipid levels before and after taking Jiang Zhi Qing Shen capsule for 12 weeks were compared.Another 30 healthy patients were enrolled in the physical examination department of Zhengzhou Hospital of Chinese Medicine,and metabolomics investigation was carried out on plasma samples of the test group before and after the treatment as well as those of the healthy patients by LC-MS/MS technology.The differences between the groups were compared by multivariate statistical analysis,and the potential biomarkers were identified by HMDB and lipidblast databases,so as to clarify the possible pathways and targets for the treatment of mild dyslipidaemia by Jiangzhi Qingshen capsules.Results Jiangzhi Qingshen capsules could improve patients' blood lipid level,BMI and abdominal circumference significantly(P<0.05).And metabolomics results showed that 29 lipid metabolites in the plasma of the treated patients were dialled back,which involved cholesterol metabolism,fat digestion and absorption,glycerol-phospholipid metabolism and other biological processes.Conclusion The efficacy of Jiangzhi Qingshen capsules in treating dyslipidaemia was confirmed,and its mechanism of action might be related to the regulation of lipid metabolism.Metabolites such as acylcarnitine(Acar),phosphatidylethanolamine(PE)and phosphatidylcholine(PC)were expected to be used as the biomarkers of dyslipidaemia,so as to provide objective scientific basis for the lipid-lowering capsule,and to facilitate the promotion of its application.

Objective:To analyze the influencing factors of mood state of common rheumatic (rheumatoid arthritis; systemic lupus erythematosus; ankylosing spondylitis) patients and find out the common characteristics of patients with negative emotions, so as to identify and treat rheumatic patients with anxiety and depression in clinical practice.Methods:A total of 205 patients with rheumatism (83 with rheumatoid arthritis, 74 with systemic lupus erythematosus, 48 with ankylosing spondylitis) admitted to the Shandong Provincial Hospital Affiliated to Shandong University from April to May 2023 were included. The general condition and POMS of patients were collected. All patients were divided into 3 groups of low-TMD/ middle-TMD/ high-TMD(TMD≤90 scores; 90 scores105 scores). The χ2 test was used for categorical variables, and the continuous variables were tested for normal distribution. If they followed a normal distribution, the independent sample t test (for homogeneous variance) or the Welch′s t test (for unequal variance) was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups; if they did not follow a normal distribution, the Kruskal-Wallis H test was used for comparison between groups. Patients with TMD>90 scores were defined as the negative emotion group. Gender, age, education level, economic income status, and TMD were included in the two-step cluster analysis (TCA) to obtain three cluster groups and analyze the differences between the groups. Logistic regression was used to analyze the risk factors. Results:The study found that patients with rheumatic diseases with low serum albumin levels ( F=6.26, P=0.003), low education level ( χ2=8.36, P=0.015), low economic level ( χ2=15.59, P<0.001), short disease course ( H=28.01, P<0.001), and high disease activity ( χ2=56.93, P<0.001) had higher TMD scores, which was not related to the type of disease ( χ2=4.81, P=0.090). The negative mood group had a higher proportion of females (57.6% vs. 73.4%, χ2=5.16, P=0.023), a shorter course of disease [24(12, 48) months vs. 48(24, 93) months, Z=13.58, P<0.001], and a lower serum albumin [(42.2±4.0) g/L vs. (44.0±3.4)g/L, t=-14.09, P=0.002], low level of education ( χ2=9.04, P=0.029), low level of income ( χ2=10.29, P=0.036), high disease activity ( χ2=61.91, P<0.001). The results of cluster analysis indicated that the above factors were significantly different among the three cluster groups except the course of disease. It is noteworthy that age ( F=19.25, P<0.001) and serum albumin ( F=5.64, P=0.004) had the lowest value and the highest TMD score ( F=5.64, P<0.001). Regression analysis showed that gender, disease course and disease activity were related factors to the occurrence of negative emotions, and high disease activity was a risk factor [ OR(95% CI) =26.58(4.53, 156.09), P<0.001]. Men [ OR(95% CI)=0.20 (0.08, 0.50), P=0.001) and the course of [ OR(95% CI)=0.99 (0.98, 1.00), P=0.007) as the protective factors. Conclusion:Male, serum albumin level, education level, income level, disease course and disease activity were the main factors affecting the mood state of patients with rheumatism, in which high disease activity was the risk factor, male and long disease course were the protective factors.

Objective:To evaluate the efficacy of gadolinium ethoxybenzyl- diethy-lenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI features in the preoperative prediction of tertiary lymphoid structures (TLS) within hepatocellular carcinoma (HCC) lesions.Methods:This retrospective cross-sectional study included clinical and pathological data from 297 HCC patients treated at the Southwest Hospital, Army Medical University between June 2021 and November 2022. Based on postoperative pathology, patients were categorized into TLS-negative ( n=93) and TLS-positive ( n=204) groups. MRI features of HCC lesions using Gd-EOB-DTPA enhancement and relevant clinical data were analyzed. Intergroup comparisons of imaging features and laboratory findings were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The logistic regression analysis was conducted to identify independent predictors of TLS positivity. A predictive model was constructed and visualized using a nomogram. The model′s predictive performance and clinical utility were assessed using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) was compared using the DeLong test. Results:Significant differences were observed between the TLS-negative and TLS-positive groups in alpha-fetoprotein (AFP) levels, intratumoral hemorrhage, and peritumoral satellite nodules in the hepatobiliary phase ( P<0.05). Multivariate logistic regression identified intratumoral hemorrhage ( OR=0.123, 95% CI 0.070-0.216, P<0.001) and peritumoral satellite nodules in the hepatobiliary phase ( OR=0.236, 95% CI 0.093-0.596, P=0.002) as independent predictive factors for TLS-positivity. The imaging model based on these two features yielded an AUC of 0.764 (95% CI 0.709-0.809) for predicting TLS-positivity. When combined with AFP levels, the resulting clinical-imaging model achieved a superior AUC of 0.784 (95% CI 0.732-0.829), which was significantly higher than that of the imaging model alone ( Z=2.20, P=0.028). A nomogram was constructed based on the clinical-imaging model. The calibration curve demonstrated good predictive performance of the nomogram, and the DCA showed that the curve remained above the default line across a range of reasonable threshold probabilities, indicating that patients could derive clinical benefit. Conclusion:A nomogram model based on Gd-EOB-DTPA enhanced MRI features combined with AFP levels can effectively predict the presence of TLS in HCC.

Objective:To analyze the influencing factors of mood state of common rheumatic (rheumatoid arthritis; systemic lupus erythematosus; ankylosing spondylitis) patients and find out the common characteristics of patients with negative emotions, so as to identify and treat rheumatic patients with anxiety and depression in clinical practice.Methods:A total of 205 patients with rheumatism (83 with rheumatoid arthritis, 74 with systemic lupus erythematosus, 48 with ankylosing spondylitis) admitted to the Shandong Provincial Hospital Affiliated to Shandong University from April to May 2023 were included. The general condition and POMS of patients were collected. All patients were divided into 3 groups of low-TMD/ middle-TMD/ high-TMD(TMD≤90 scores; 90 scores105 scores). The χ2 test was used for categorical variables, and the continuous variables were tested for normal distribution. If they followed a normal distribution, the independent sample t test (for homogeneous variance) or the Welch′s t test (for unequal variance) was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups; if they did not follow a normal distribution, the Kruskal-Wallis H test was used for comparison between groups. Patients with TMD>90 scores were defined as the negative emotion group. Gender, age, education level, economic income status, and TMD were included in the two-step cluster analysis (TCA) to obtain three cluster groups and analyze the differences between the groups. Logistic regression was used to analyze the risk factors. Results:The study found that patients with rheumatic diseases with low serum albumin levels ( F=6.26, P=0.003), low education level ( χ2=8.36, P=0.015), low economic level ( χ2=15.59, P<0.001), short disease course ( H=28.01, P<0.001), and high disease activity ( χ2=56.93, P<0.001) had higher TMD scores, which was not related to the type of disease ( χ2=4.81, P=0.090). The negative mood group had a higher proportion of females (57.6% vs. 73.4%, χ2=5.16, P=0.023), a shorter course of disease [24(12, 48) months vs. 48(24, 93) months, Z=13.58, P<0.001], and a lower serum albumin [(42.2±4.0) g/L vs. (44.0±3.4)g/L, t=-14.09, P=0.002], low level of education ( χ2=9.04, P=0.029), low level of income ( χ2=10.29, P=0.036), high disease activity ( χ2=61.91, P<0.001). The results of cluster analysis indicated that the above factors were significantly different among the three cluster groups except the course of disease. It is noteworthy that age ( F=19.25, P<0.001) and serum albumin ( F=5.64, P=0.004) had the lowest value and the highest TMD score ( F=5.64, P<0.001). Regression analysis showed that gender, disease course and disease activity were related factors to the occurrence of negative emotions, and high disease activity was a risk factor [ OR(95% CI) =26.58(4.53, 156.09), P<0.001]. Men [ OR(95% CI)=0.20 (0.08, 0.50), P=0.001) and the course of [ OR(95% CI)=0.99 (0.98, 1.00), P=0.007) as the protective factors. Conclusion:Male, serum albumin level, education level, income level, disease course and disease activity were the main factors affecting the mood state of patients with rheumatism, in which high disease activity was the risk factor, male and long disease course were the protective factors.

ObjectiveThis paper aims to analyze the current status of outcome indicators in randomized controlled trials （RCT） of traditional Chinese medicine （TCM） for treating chronic atrophic gastritis （CAG）， so as to provide references for constructing the core outcome set （COS） of TCM in the treatment of CAG. MethodChina National Knowledge Infrastructure （CNKI）， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library databases were searched for RCTs of TCM in the treatment of CAG in the last five years. The risk of bias of included studies was evaluated， and the selection status of outcome indicators was statistically analyzed. ResultA total of 150 RCTs were included， with a sample size of 44-398 cases. 164 outcome indicators were reported， with an application frequency of 1 229 times. The outcome indicators were classified into seven indicator domains according to functional attributes， followed by physical and chemical examination （69.41%）， TCM syndrome （12.69%）， symptoms and signs （11.15%）， safety indicators （5.37%）， quality of life （0.65%）， long-term prognosis （0.65%）， and economic evaluation （0.08%）. According to the statistical analysis， there were problems in the selection of outcome indicators in RCTs of TCM for treating CAG， including various indicators， non-standard name reports， unclear primary and secondary indicators， random combination of subjective and objective indicators， neglected patient report outcome indicators， missing long-term prognosis and economic indicators， insufficient reporting of safety indicators， and inconsistent measurement tools and measurement time points. ConclusionIn the past five years， there have been many problems in the selection of outcome indicators in RCTs of TCM for treating CAG. It is necessary to actively promote the construction of the COS of TCM in the treatment of CAG and promote the high-quality development of clinical research of TCM.

In this study, 34 deep eutectic solvents (DESs) were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes. The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis. The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30% (V/V) in DESs. AB-8 macroporous resin and ethyl acetate were used for separation and refining, and the oligomer-rich proanthocyanidin components were eventually obtained. The ultraviolet (UV) and infrared (IR) spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin. To further clarify the chemical composition of proanthocyanidin, an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering (MDF) algorithm, combined with the full mass spectrometry (MS)/dd-MS² scan mode that turns on the "if idle pick others" function. By using ultra-high performance liquid chromatography and high-resolution MS (UHPLC/HRMS), the analysis used both targeted and non-targeted methods to detect proanthocyanidins. Finally, 50 oligomeric proanthocyanidin (OPC) compounds were identified, including 7 monomers, 22 dimers, 20 trimers, and 1 tetramer, most of which were procyanidins of proanthocyanidins (84%), and a small amount of prodelphinidin (14%) and other types of proanthocyanidins (2%), which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes. Meanwhile, the comparison with the grape seeds OPCs standard (United States Pharmacopeia) revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant, suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.