ObjectiveTo investigate the mechanism by which Bushao Tiaozhi capsules （BSTZ） ameliorate hyperlipidemia based on untargeted metabolomics and targeted bile acid quantification. MethodsA rat model of hyperlipidemia was established with a high-fat diet. The rats were randomized into five groups： normal control， model， atorvastatin calcium （1.8 mg·kg^-1）， and low-dose （2.88 g·kg^-1） and high-dose （5.76 g·kg^-1） BSTZ groups. All treatments were administered for four consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by biochemical assays. Hepatic histopathological changes were evaluated via hematoxylin-eosin （HE） staining， and lipid droplet deposition was assessed by oil red O staining. Integrated untargeted metabolomics and targeted bile acid quantification were employed to investigate BSTZ-induced alterations in hepatic metabolic profile and bile acid profile. Additionally， correlation analyses were conducted between differential bile acids and lipid parameters to identify key bile acids. ResultsCompared with the normal control group， the model group exhibited elevated serum TC， TG， and LDL-C levels （P<0.01） and a reduced HDL-C level （P<0.01）， along with marked hepatic steatosis and extensive lipid droplet deposition. Compared with the model group， all BSTZ treatment groups showed decreased TC， TG， and LDL-C levels （P<0.01） and increased HDL-C levels （P<0.01）， accompanied by notably alleviated hepatic steatosis and lipid deposition. Untargeted metabolomics and targeted bile acid quantification revealed that BSTZ significantly remodeled the hepatic bile acid profile， characterized by elevated levels of secondary bile acids （DCA， HDCA， TDCA， and TLCA） and reduced levels of primary bile acids （CDCA and TCDCA）. Correlation analyses further demonstrated strong associations between differential bile acids and lipid parameters： elevated secondary bile acids were negatively correlated with serum TC， TG， and LDL-C levels， whereas primary bile acids were positively correlated with these parameters. ConclusionBSTZ can ameliorate dyslipidemia and hepatic lipid accumulation in hyperlipidemic rats by regulating hepatic bile acid homeostasis， which provides metabolic clues for subsequent mechanism validation.

Objective:To explore the value of a scoring system based on preoperative abdominal computed tomography (CT) for predicting the difficulty of laparoscopic cholecystectomy (LC).Methods:A retrospective analysis was conducted on 105 patients diagnosed with gallstones or cholecystitis who underwent LC at Beijing Jishuitan Hospital, Capital Medical University from January 2021 and February 2022. Based on surgical video reviews, patients were divided into the easy group ( n=58) and the difficult group ( n=47) according to the intraoperative Parkland Grading Scale (PGS), with PGS grades 1-2 assigned to the easy group, and PGS grades 3-5 assigned to the difficult group. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and compared using independent samples t-test; the non-normally distributed measurement data were expressed as median (interquartile range) [ M ( Q1, Q3)], and compared using the rank-sum test. The count data were expressed as the number of cases and percentage, and compared using the Chi-square test or Fisher exact probability method. Univariate analysis and cut-off value determination: for continuous CT variables, univariate Logistic regression and stepwise regression analyses (with surgical difficulty grouping as the dependent variable) were performed to identify the optimal combination of predictive variables and establish a scoring system. For each significantly associated continuous variable or important CT image feature from a clinical perspective, receiver operating characteristic (ROC) curve analysis was used to evaluate its predictive performance for difficult surgery. The area under the curve (AUC) was calculated, and the optimal cut-off value was determined using the Youden index to maximize the sum of sensitivity and specificity. The categorical CT image features were scored according to their original groups. The Kappa consistency test was used to assess the strength of agreement between the preoperative abdominal CT score (grouped by the optimal cut-off) and PGS grades (easy/difficult). Decision curve analysis (DCA) was employed to validate the predictive performance of the model. Results:Stepwise Logistic regression identified seven key imaging features as the optimal predictive variables for constructing the preoperative abdominal CT scoring system: maximum gallbladder cross-sectional diameter, maximum gallbladder cross-sectional width, gallbladder wall thickness, common bile duct diameter, pericholecystic fat stranding, periductal fat stranding, and impacted cystic duct stones. Each case was scored after assigning scores based on the optimal cut-off values. The total score of the preoperative abdominal CT scoring system was ≥3 points predicted difficult LC with an AUC of 0.745 (95% CI: 0.650-0.839), sensitivity of 66.0%, and specificity of 75.9%. DCA confirmed the model′s reliable predictive performance, and the preoperative abdominal CT scoring system showed good agreement with PGS grades ( Kappa value was 0.420, P<0.001). Conclusions:The preoperative abdominal CT scoring system based on pericholecystic imaging features can effectively predict the difficulty of LC with good discriminative ability. It provides a quantitative tool for preoperative assessment, surgical scheduling, and ambulatory surgery management.

Objective:To evaluate the association between the preoperative aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:In this nested case-control study, medical records from patients, aged ≥55 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with Mini-Mental State Examination (MMSE) scale score >24 on preoperative day 1, scheduled for elective total knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between November 2021 and December 2023, were collected. POD was assessed using the Confusion Assessment Method. Patients were categorized into POD and non-POD groups based on the occurrence of POD. Logistic regression was employed to identify protective and risk factors for POD. The predictive performance of preoperative AST/ALT ratio alone and its combination with cerebrospinal fluid (CSF) biomarker concentrations for POD was evaluated using receiver operating characteristic curves, and the clinical utility of the prediction models was assessed using decision curve analysis. Mediation analysis was conducted to examine the mediation role of CSF biomarkers in the relationship between the preoperative AST/ALT ratio and POD. Restricted cubic splines were used to assess the nonlinear relationship between the preoperative AST/ALT ratio and POD.Results:A total of 460 patients were finally included, with 49 in POD group and 411 in non-POD group. After adjustment for multiple confounding factors including age, sex, educational level, MMSE score, history of hypertension, history of diabetes, history of smoking and history of alcohol use, multivariable logistic regression identified that the higher preoperative AST/ALT ratio, CSF total tau protein (t-tau) and phosphorylated tau protein (p-tau) concentrations were independent risk factors for POD, whereas lower CSF β-amyloid 42 (Aβ 42) concentration, Aβ 42/t-tau ratio and Aβ 42/p-tau ratio served as protective factors ( P<0.05). The area under the receiver operating characteristic curve of the preoperative AST/ALT ratio combined with CSF biomarkers in predicting POD was 0.939 ( P<0.001), demonstrating high clinical efficacy. After adjusting for age, educational level, sex, MMSE score, history of hypertension, history of diabetes, history of smoking, history of alcohol use and body mass index, restricted cubic splines revealed a nonlinear relationship between preoperative AST/ALT levels and the probability of POD, and the probability of POD increased with rising ratios when the preoperative AST/ALT ratio ranged from 1.09 to 1.40 ( Poverall < 0.05, Pnonlinear <0.05). After stratification by sex, the preoperative AST/ALT ratio demonstrated a linear relationship with the probability of POD ( Poverall <0.05, Pnonlinear>0.05). Mediation analysis indicated that the relationship between the preoperative AST/ALT ratio and POD was partially mediated by CSF p-tau concentration (proportion mediated 18.1%), CSF t-tau concentration (proportion mediated 12.0%), and the Aβ 42/t-tau ratio (proportion mediated 15.4%). Conclusions:A higher preoperative AST/ALT ratio is an independent risk factor for POD in total knee/hip arthroplasty patients. The concentrations of CSF t-tau and p-tau and Aβ 42/t-tau ratio have a mediating role in the relationship between the preoperative AST/ALT ratio and POD.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Objective To investigate the efficacy and safety of blank microspheres combined with microcoils in treating hemopty-sis due to arteriae bronchiales(BA)malformation during bronchial arterial embolization(BAE).Methods A retrospective analysis was conducted on the preoperative data,embolization materials,technical success rate,clinical success rate,postoperative recurrence rate,and complications of 87 patients who underwent BAE using blank microspheres for hemoptysis due to BA malformation.Results There were 87 patients in this study,and BA computed tomography angiography(CTA)classification was as follows:32 cases(36.78％)of type Ⅰ,23 cases(26.44％)of type Ⅱ,19 cases(21.84％)of type Ⅲ,and 13 cases(14.94％)of other types(Ⅳ-Ⅸ).A total of 171 blood vessels were embolized in 87 patients,including 16 ectopic BA,and 130 embolized microspheres,including 104 microspheres of 500-700 μm and 26 of 700-900 μm.There were 265 microcoils,with a technical success rate of 100％,a 24 h clinical success rate of 100％,and a 30 d clinical success rate of 98.85％.The recurrence rate was 3.45％ at 6 months,5.75％ at 12 months,and 8.05％ at 24 months.Postopera-tive complications(Clavien-Dindo classification):complications of grade Ⅰ,embolic syndrome recurrence rate was 8.05％,chest pain incidence was 3.45％,dysphagia incidence was 2.30％,BA injury incidence was 3.45％;complications of grade Ⅳ,paraplegia inci-dence was 1.15％.Conclusion The use of blank microspheres combined with microcoils in the treatment of hemoptysis caused by BA malformation has high safety and clear efficacy.

OBJECTIVE: To compare clinical efficacy of tibial transverse transport (TTT) microcirculation reconstruction and periosteal distraction in treating patients with early diabetic foot(DF). METHODS: From June 2021 to June 2024, 60 patients with DF were admitted and divided into bone transport group and stretch group according to different treatment methods. There were 30 patients in bone transport group, including 16 males and 14 females;aged from 48 to 65 years old with an average of (55.59±3.78) years old;the course of disease ranged from 2 to 9 months with an average of(5.95±1.32) months;TTT microcirculation reconstruction surgery was performed. There were 30 patients in distraction group, including 17 males and 13 females;aged from 47 to 67 years old with an average of (55.24±3.81) years old;the course of disease ranged from 2 to 10 months with an average of (5.68±1.54) months;periosteal distraction surgery was performed. The skin temperature of the affected feet, the time of getting out of bed and walking after operation, the time of full weight-bearing, the wound healing time and complications were compared between two groups;the pain was evaluated by visual analogue scale (VAS) before operation and one month after operation respectively;the changes of blood flow velocity of dorsal foot arteries, ankle brachial index(ABI), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF) before and after operation at 3 months were compared between two groups. RESULTS: All patients were followed up for 3 to 4 months with an average of (3.52±0.12) months. There were no statistically significant differences in comparison of foot skin temperature, postoperative walking time, full weight-bearing time and complications between two groups (P>0.05). The wound healing time of bone transport group (61.26±7.31) days was shorter than that of distraction group (70.17±7.15) days, and the difference was statistically significant (P<0.05). Postoperative VAS at 1 month of bone transport group (2.19±0.21) was lower than that of distraction group (2.55±0.20), and the difference was statistically significant (P<0.05). At 3 months after operation, the blood flow velocity of dorsal foot artery, ankle-brachial index, EGF and bFGF in bone transport group were(34.73±4.18) cm·s^-1, (0.95±0.13), (716.61±71.13) pg·ml^-1 and (175.69±31.28) pg·ml^-1, respectively;which were higher than that of distraction group (31.86±3.23) cm·s^-1, (0.84±0.11), (677.37±70.21) pg·ml^-1, (149.26±30.13) pg·ml^-1, and the differences were statistically significant (P<0.05). There was no recurrence of ulcers in situ or at other sites in both groups during follow-up. CONCLUSION Compared with periosteal distraction, TTT microcirculation reconstruction surgery has a definite effect in the treatment of early DF. It could effectively reduce pain level, improve blood flow indicators and vascular endothelial function of the foot, and has a relatively high safety.
Humans ; Male ; Female ; Middle Aged ; Aged ; Tibia/blood supply* ; Diabetic Foot/physiopathology* ; Microcirculation ; Periosteum/surgery* ; Plastic Surgery Procedures/methods* ; Osteogenesis, Distraction

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Objective:To evaluate the association between the preoperative aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:In this nested case-control study, medical records from patients, aged ≥55 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with Mini-Mental State Examination (MMSE) scale score >24 on preoperative day 1, scheduled for elective total knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between November 2021 and December 2023, were collected. POD was assessed using the Confusion Assessment Method. Patients were categorized into POD and non-POD groups based on the occurrence of POD. Logistic regression was employed to identify protective and risk factors for POD. The predictive performance of preoperative AST/ALT ratio alone and its combination with cerebrospinal fluid (CSF) biomarker concentrations for POD was evaluated using receiver operating characteristic curves, and the clinical utility of the prediction models was assessed using decision curve analysis. Mediation analysis was conducted to examine the mediation role of CSF biomarkers in the relationship between the preoperative AST/ALT ratio and POD. Restricted cubic splines were used to assess the nonlinear relationship between the preoperative AST/ALT ratio and POD.Results:A total of 460 patients were finally included, with 49 in POD group and 411 in non-POD group. After adjustment for multiple confounding factors including age, sex, educational level, MMSE score, history of hypertension, history of diabetes, history of smoking and history of alcohol use, multivariable logistic regression identified that the higher preoperative AST/ALT ratio, CSF total tau protein (t-tau) and phosphorylated tau protein (p-tau) concentrations were independent risk factors for POD, whereas lower CSF β-amyloid 42 (Aβ 42) concentration, Aβ 42/t-tau ratio and Aβ 42/p-tau ratio served as protective factors ( P<0.05). The area under the receiver operating characteristic curve of the preoperative AST/ALT ratio combined with CSF biomarkers in predicting POD was 0.939 ( P<0.001), demonstrating high clinical efficacy. After adjusting for age, educational level, sex, MMSE score, history of hypertension, history of diabetes, history of smoking, history of alcohol use and body mass index, restricted cubic splines revealed a nonlinear relationship between preoperative AST/ALT levels and the probability of POD, and the probability of POD increased with rising ratios when the preoperative AST/ALT ratio ranged from 1.09 to 1.40 ( Poverall < 0.05, Pnonlinear <0.05). After stratification by sex, the preoperative AST/ALT ratio demonstrated a linear relationship with the probability of POD ( Poverall <0.05, Pnonlinear>0.05). Mediation analysis indicated that the relationship between the preoperative AST/ALT ratio and POD was partially mediated by CSF p-tau concentration (proportion mediated 18.1%), CSF t-tau concentration (proportion mediated 12.0%), and the Aβ 42/t-tau ratio (proportion mediated 15.4%). Conclusions:A higher preoperative AST/ALT ratio is an independent risk factor for POD in total knee/hip arthroplasty patients. The concentrations of CSF t-tau and p-tau and Aβ 42/t-tau ratio have a mediating role in the relationship between the preoperative AST/ALT ratio and POD.

Objective To investigate the efficacy and safety of blank microspheres combined with microcoils in treating hemopty-sis due to arteriae bronchiales(BA)malformation during bronchial arterial embolization(BAE).Methods A retrospective analysis was conducted on the preoperative data,embolization materials,technical success rate,clinical success rate,postoperative recurrence rate,and complications of 87 patients who underwent BAE using blank microspheres for hemoptysis due to BA malformation.Results There were 87 patients in this study,and BA computed tomography angiography(CTA)classification was as follows:32 cases(36.78％)of type Ⅰ,23 cases(26.44％)of type Ⅱ,19 cases(21.84％)of type Ⅲ,and 13 cases(14.94％)of other types(Ⅳ-Ⅸ).A total of 171 blood vessels were embolized in 87 patients,including 16 ectopic BA,and 130 embolized microspheres,including 104 microspheres of 500-700 μm and 26 of 700-900 μm.There were 265 microcoils,with a technical success rate of 100％,a 24 h clinical success rate of 100％,and a 30 d clinical success rate of 98.85％.The recurrence rate was 3.45％ at 6 months,5.75％ at 12 months,and 8.05％ at 24 months.Postopera-tive complications(Clavien-Dindo classification):complications of grade Ⅰ,embolic syndrome recurrence rate was 8.05％,chest pain incidence was 3.45％,dysphagia incidence was 2.30％,BA injury incidence was 3.45％;complications of grade Ⅳ,paraplegia inci-dence was 1.15％.Conclusion The use of blank microspheres combined with microcoils in the treatment of hemoptysis caused by BA malformation has high safety and clear efficacy.

Objective To determine the risk factors and prognostic survival of patients with para-aortic lymph node metastasis of advanced esophagogastric junction malignancy by comparing their general clinicopathological characteristics and regional lymph node metastasis status with those of patients with negative para-aortic lymph node metastasis. Methods This single-center retrospective case study collected the clinical and pathological data of 224 patients with esophagogastric junction malignant tumors undergoing radical resection. Single factor affecting lymph node metastasis in group 16 was analyzed by chi square test, and multiple factors were examined using logistic regression. Kaplan-Meier method was used for survival analysis, and Log rank test was used for survival rate comparison. Results Among the 224 patients with advanced esophagogastric junction malignant tumors, (1) Univariate analysis showed that Siewert classification, tumor diameter, pathological stage, T stage, and N stage were associated with positive para-aortic lymph node metastasis (P<0.05). Meanwhile, multivariate logistic analysis showed that Siewert type and tumor diameter were independent risk factors for positive metastasis (P<0.05); (2) Among the 17 groups of regional lymph nodes with para-aortic lymph node metastasis, univariate analysis revealed that No.5, No.6, No.111, and No.112 lymph nodes were not correlated with positive para-aortic lymph node metastasis (P>0.05). The remaining 13 groups of regional lymph nodes were all associated with para-aortic lymph node metastasis. Meanwhile, multivariate logistic analysis revealed that No.7, No.11p, and No.110 lymph nodes were independent risk factors for metastasis (P<0.05). When the regional lymph node metastasis in these three groups was negative, the positive rate of para-aortic lymph node metastasis was only 4.7%. When at least one of these groups had regional lymph node metastasis, the positive metastasis rate was up to 47.4%; (3) The 1- and 3-year cumulative survival rates of the patients with positive para-aortic lymph node metastasis after surgery were 76.5% and 8.1%, respectively, and those in negative patients were 98.3% and 76.8%, respectively. Log rank test showed a significant difference in overall survival rate between the patients with positive and negative para-aortic lymph node metastasis (P<0.001). Conclusion (1) Preoperative examination of patients with advanced esophagogastric junction malignant tumors should clarify the tumor type and maximum diameter. Patients with Siewert type Ⅱ and Ⅲ and maximum tumor diameter of >6 cm are recommended to undergo para-aortic lymph node dissection. (2) Frozen biopsy of lymph nodes of No.7 and No.11p is performed during the operation, and the para-aortic lymph nodes should be dissected if the metastasis is found to be positive, which is helpful for the clinical surgeon to judge the dissection of the para-aortic lymph nodes.