Hepatopulmonary syndrome (HPS) is characterized by inflammation, pulmonary vasodiation and angiogenesis. Elevated serum level of fatty acid binding protein 4 (FABP4) in patients with liver cirrhosis is associated with poor prognosis, and FABP4 is involved in the regulation of inflammation and angiogenesis. Using a bile duct ligation (BDL) -induced HPS rat model and the FABP4inhibitor BMS309403 for intervention, this study aims to investigate the role of the FABP4/PPAR-γ signaling axis in the pathogenesis of HPS and to evaluate the protective mechanism of FABP4 inhibition against hepatopulmonary injury.

A total of 24 male SPF SD rats (6 to 8 weeks old, weighing 200 to 220 g) were enrolled and randomly divided into (n=6): a sham operation group (Sham group), the BDL postoperative3-week group (BDL3W group), the BDL postoperative 5-week group (BDL5W group), and a BDL+BMS309403treatment group (BDLB group). The BDL3W, BDL5W and BDLB groups underwent BDL to establish an HPS model, while the Sham group underwent only bile duct manipulation without ligation. The BDLB group received intraperitoneal injections of BMS309403 (5 mg/kg, twice per week) from postoperative day 15 for3 weeks. The BDL3W group was sacrificed at week 3 post-surgery, while the Sham, BDL5W, and BDLB groups were sacrificed at week 5 post-surgery. Histopathological changes in the liver and lung tissues were evaluated using HE staining. The severity of hepatic fibrosis was assessed by Masson ' s trichrome staining, while hepatic lipid accumulation was examined using Oil Red O staining. Microarray was performed on lung tissues from the Sham and BDL3W groups, and integrated analysis of differentially expressed genes (DEGs) was conducted, including: heatmap plotting based on specific gene sets, visualization of differential expression with volcano plots, and GO functional enrichment analysis. Immunohistochemistry was used to detect the localization and expression levels of CD31, iNOS, TNF-α, NF-κB p65, and PPAR-γ in lung tissues. Immunofluorescence staining was performed to determine the expression of FABP4. The protein levels of FABP4 and PPAR-γ in lung tissues were quantified by Western blotting. Arterial blood gas analysis was conducted to measure PaO₂ and P(A-a)O₂ for the evaluation of pulmonary function, and serum levels of ALT and AST were determined to evaluate hepatic function.

① Compared with the BDL3W group, the BDL5W group exhibited progressively disorganized liver structure, gradually aggravated fibrosis, and a significant increase in relative collagen areas (P<0. 01). Serum ALT levels increased continuously from the Sham group to the BDL3W and BDL5W groups (P<0. 01), with AST levels showing the same trend (P<0. 01). In the lungs, inflammatory cell infiltration aggravated progressively, and PaO₂ decreased gradually from the Sham to BDL3W and BDL5W groups (P<0. 05). Compared with the BDL3W group, P(A-a)O₂ was markedly elevated in the BDL5W group (P<0. 01), confirming the successful establishment of the HPS model. ② In the BDL3W group, FABP4 gene was significantly upregulated in the lung tissues (FC≥1. 5, P≤0. 05). GO enrichment analysis revealed significant enrichment of lipid metabolism-related genes, suggesting that FABP4and lipid metabolic processes play important roles in the pulmonary pathogenesis during HPS. ③ Compared with the BDL5W group, the BDLB group showed significantly decreased serum AST and ALT levels (P<0. 01), accompanied by attenuated hepatic fibrosis, as evidenced by a significant reduction in relative collagen area (P<0. 01). Pulmonary inflammatory infiltration, hemorrhage, and atelectasis were alleviated, with a significant increase in PaO₂ (P<0. 01) and an obvious decrease in P(A-a)O₂ (P<0. 01). ④ Immunofluorescence and Western blotting revealed that FABP4 expression in the lung tissues of the BDLB group was significantly lower than that in the BDL5W group (P<0. 05). Immunohistochemistry and Western blotting further demonstrated that PPAR-γ expression in the lung tissues was significantly enhanced in the BDLB group compared with the BDL5W group (P<0. 05). ⑤ Compared with the BDL5W group, the BDLB group exhibited reduced hepatic lipid droplet accumulation. Immunohistochemical analysis showed a significant decrease in the diameter of pulmonary microvascular lumens (P<0. 01), along with significantly downregulated expression of iNOS (P<0. 01), and remarkably reduced expression levels of the inflammatory factors TNF-α and NF-κB p65 (P<0. 01).

The FABP4 inhibitor BMS309403 ameliorates hepatopulmonary pathological injury and improves hypoxemia in HPS rats by modulating the FABP4/PPAR-γ signaling axis, ameliorating hepatic lipid metabolism disorder, inhibiting NF- κB p65/TNF- α -mediated pulmonary inflammatory response, and suppressing iNOS/NO-driven pulmonary microvascular dilation.

To identify risk factors for postoperative respiratory failure (PORF) in cardiovascular surgery patients using machine learning algorithms and to construct a specific risk prediction model.

A retrospective cohort was conducted on 1623 patients undergoing cardiovascular surgery between 2011 and 2020 from the INSPIRE database. Following data quality analysis, multiple imputation was employed to handle missing data, and the Boruta algorithm was used for feature selection. Eight machine learning models were constructed based on the selected features, including Gradient Boosting Machine (GBM), Generalized Linear Model (GLM), Extreme Gradient Boosting (XGBoost), K-Nearest Neighbors (KNN), Neural Network (NNET), Naive Bayes (NB), Support Vector Machine (SVM), and Random Forest (RF). Model performance was evaluated using metrics including the area under the curve (AUC), sensitivity, and specificity. Variables significantly influencing PORF were identified using the permutation importance algorithm.

The overall incidence of PORF was 27.05% (439/1623). The in-hospital mortality rate was significantly higher in the PORF group than the non-PORF group (12.98% vs 1.60%, P<0.001). Among the developed models, the SVM model demonstrated the best performance, achieving an AUC of 0.705 in the testing set, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.481, 0.825, 0.504, and 0.812, respectively. Based on feature importance analysis, the top 10 variables most predictive of PORF were anesthesia duration, arterial partial pressure of carbon dioxide (PaCO₂), calcium level, lymphocyte percentage, cardiopulmonary bypass duration, intraoperative blood loss, age, creatinine level, aspartate aminotransferase (AST) level, and activated partial thromboplastin time (aPTT).

A predictieon model for PORF following cardiovascular surgery is successfully developed. This model can identify high-risk patients and estimate their probability of developing respiratory failure, thereby facilitating data-driven clinical decision-making.

Patients with chronic liver diseases often exhibit unique hemodynamic abnormalities and metabolic disorders. Postoperative fluid management presents numerous challenges, especially for critically ill patients admitted to the intensive care unit (ICU) after surgery. This study aimed at exploring the relationship between postoperative fluid therapy and prognosis.

Based on 2414 patients with chronic liver diseases who underwent surgical treatment and were subsequently transferred to the ICU in the MIMIC-Ⅳ database, a retrospective cohort study was conducted on the final 2143 patients after our inclusion and exclusion criteria. Multivariate adjusted logistic regression model was used to analyze the association between fluid therapeutic regimens on the first day after ICU admission and the risk of 7-day death after surgery. Restricted cubic spline (RCS) was applied to analyze the dose-response relationship.

Multivariate analysis indicated that restrictive fluid resuscitation was an independent protective factor. Compared with the non-restrictive fluid resuscitation group, restrictive fluid resuscitation significantly reduced the 7-day postoperative mortality rate (6.4% vs 12.4%, OR=0.44, 95%CI: 0.22~0.88, P=0.021), decreased the use of mechanical ventilation (42.9% vs 72.3%, OR=0.29, 95%CI: 0.24~0.35, P<0.001), and shortened the ICU stay (1.86 vs 3.47 d, OR=0.81, 95%CI: 0.78~0.84, P<0.001). RCS curve showed that the fluid intake on the first postoperative day and the 7-day postoperative mortality risk presented a J-shaped curve relationship, with an inflection point at 1850 mL. Beyond this threshold, the 7-day postoperative mortality risk was increased. Subgroup analysis results indicated that the protective effect of restrictive fluid resuscitation was consistent across different age and comorbidity groups.

For patients with chronic liver diseases, adopting a restrictive fluid therapy on the first day after surgery can effectively reduce the risk of short-term death. Moreover, there is a non-linear dose-effect relationship between the fluid intake and the 7-day mortality risk. When the fluid intake exceeds 1850 mL, the risk of death significantly increases.

To investigate the effects of niclosamide on S100A4 expression and pathological angiogenesis of hepatopulmonary syndrome（HPS）in rats.

Thirty male SD rats were randomly divided into control group（Sham group, n=6）, common bile duct ligation（CBDL）group（n=18）and niclosamide treatment group（NIC group, n=6）. The rats of the NIC group were gavaged with niclosamide suspension for 1 week since the first day of the third week after modelling, and the rats were dissected at the end of the fifth week to assess the pathological changes and disease progression of liver and lung tissues by HE and Masson staining. Immunofluorescence assay was used to detect the location and intensity of S100A4 and CD31 expression in the lung of rats. The expression of S100A4 at mRNA and protein levels was detected using qPCR and Western blotting. Pulmonary microvascular endothelial cells（PMVECs）were treated with small interfering RNA（siRNA）serum of HPS rats and nichosamide, respectively, and their effects on cell migration and tube-forming abilities were observed.

Both mRNA and protein expression of S100A4 in lung tissue of the CBDL group rats were increased with disease progression, and the expression levels were higher than those in the Sham group（P<0.000 1）; The lung mRNA and protein levels of S100A4 were lower in the NIC group than the CBDL group at the 5th week, but still higher than those in the Sham group. After knockdown of S100A4 using siRNA in PMVECs, the migration and tube-forming abilities were reduced when compared with the NC group（P<0.000 1）. HE staining displayed that pulmonary pathological changes were milder in the NIC group than the CBDL group at the 5th week, while no such effect was found in the liver tissues. Masson staining showed that hepatic fibrosis was not obviously ameliorated in the NIC group. The migration and tube-forming abilities of the cells was significantly increased in the CBDL group after the 5 weeks of serum stimulation compared to the Sham rats, while niclosamide treatment reversed this phenomenon（P<0.000 1）.

S100A4 can accelerate the progression of HPS by promoting pulmonary micro-angiogenesis in HPS rats, and niclosamide inhibits the expression of S100A4 in the lung and thus delays the progression of HPS.

To establish a risk model for predicting postoperative cognitive dysfunction（POCD）after non-cardiac surgery using preoperative indicators based on machine learning algorithm.

A case-control study was designed, and conducted on the POCD patients after non-cardiac surgery in the medical big data platform of our hospital from January 2014 to January 2019. Finally, 92 patients were included in the POCD group. According to surgical type and age matched of the POCD group, another 276 patients who did not develop POCD after surgery and discharged from the hospital during the same time period from the same big data platform were assigned into the non-POCD group at a ratio of 1∶3. At the same time, these 368 patients were randomly divided into modeling group（n=259）and validation group（n=109）at a ratio of 7∶3. After data preprocessing and feature selection of preoperative clinical indicators（general data, relevant scoring scales, surgical-related data and results of preoperative laboratory tests）, the risk prediction model of POCD for non-cardiac surgery was established based on 3 machine learning algorithms, that is, logistic regression（LR）, support vector machine（SVM）and Decision Tree. The model efficacy was evaluated by sensitivity, specificity, F1 score, and the area under the receiver operating characteristic curve（AUC）.

The SVM algorithm was the best model among the 3 machine learning algorithms to predict the risk of POCD after non-cardiac surgery. The AUC value of the model in the validation group was 0.957（95%CI: 0.905~1.000）, with a sensitivity and specificity of 92.6% and 98.8%, respectively.

A prediction model of POCD after non-cardiac surgery is successfully established based on machine learning algorithm. This model shows good predictive performance for POCD.

To develop and validate a machine learning prediction model for postoperative respiratory failure（PRF）in patients after non-cardiothoracic surgery based on intraoperative indicators.

A total of 705 patients undergoing non-cardiothoracic surgery in our hospital from January 2014 to June 2019 were enrolled, and then 565 patients of them were assigned in the training set（including 128 cases of PRF）and 140 patients into the test set（35 cases of PRF）. Another 164 patients undergoing non-cardiothoracic surgery at West China Hospital from May 2019 to January 2020 and Zhongshan Hospital from June 2019 to December 2019 were assigned into the validation set（41 cases of PRF）. Nineteen intraoperative indicators were extracted, and 6 machine learning algorithms, such as gradient boosting model（GBM）, generalize linear model（GLM）, k-nearest neighbor（KNN）, naive bayes（NB）, neural network（NNET）, and support vector machine linear（SVM）were used to develop and test the models and were verified in the validation set. The best model was screened out by comparing the performance of each model, and finally, the web page prediction model was established.

GBM obtained the best performance, with an accuracy of 76.2%（95%CI: 69.0%~82.5%）, an area under the subject curve（AUC）of 0.794（95%CI: 0.707~0.882）, an area under the precision-recall curve（AUPRC）of 0.641, and a Brier score of 0.169.

The model developed based on GBM algorithm is of higher generalization, accuracy, and clinical utility, and helps avoid overfitting. The developed web page prediction model（http://150.158.55.139）can provide a new dynamic evaluation method for PRF and quantify surgical risk.

To investigate the differences in brain oxygen supply-demand balance before and after intravenous anesthesia with propofol, and determine the influencing factors of the balance and cerebral autoregulation plateau.

A total of 53 patients undergoing open hepatobiliary surgery in our hospital from June 2020 to October 2020 were enrolled in this study. Their local regional cerebral oxygen saturation (rSO₂), cerebral tissue hemoglobin concentration index (THI) and mean arterial pressure (MAP) were monitored and recorded from entering the operating room to the end of the operation. Brain oxygenation was assessed using rSO₂ as well as using THI. Then the moving linear Pearson correlation coefficient between rSO₂ and MAP was calculated and named as Cox, and the moving linear Pearson correlation coefficient between THI and MAP was also calculated and named as THx. The upper and lower limits and range of cerebral autoregulation (CA) were studied using COx and THx. Intermittent sampling of blood was performed for blood gas analysis. All patients underwent standardized anesthesia management.

There were significant differences in rSO₂ in the left and right brain before and after anesthesia (left: P<0.001, right: P<0.001), so were in THI in the left and right sides before and after anesthesia (left: P<0.001, right: P<0.001). There were no statistical differences in the left and right rSO₂ and THI among those at different ages, with the porta hepatis being blocked or not, and with different operation durations (P>0.05). Linear correlation curve showed that the THI values of the left and right brain were decreased with age (left: r=-0.261 8, P=0.058 3; right: r=-0.283 6, P=0.039 6). Under propofol intravenous anesthesia, COx defined the lower limit, upper limit and range of CA were 81.98±12.63, 93.67±13.69 and 11.22±8.38 mmHg, respectively. THx defined the lower limit, upper limit and range of CA was 79.96±10.61, 93.77±12.34 and 13.79±8.63 mmHg, respectively. No obvious differences were seen in the upper limit, lower limit and adjustment range of CA defined by COx and THx among those with the age is older than 50 years or not, porta hepatis being blocked or not, and longer than 360 min or not (P>0.05).

Propofol anesthesia can induce declined rSO₂ and THI values in the left and right brain. The left and right cerebral THI is affected by age, while the lower limit, upper limit and range of CA are not affected by the age older than 50 years, the porta hepatis being blocked or not, and the operation time longer than 360 min or not.

To investigate the protective effect of blebbistatin, a non-muscle myosin Ⅱ (NMⅡ) inhibitor, on inflammatory injury of lung tissue after chronic common bile duct ligation (CBDL) in rats.

A total of 55 SPF male SD rats (200~220 g) were randomly divided into 3 groups, namely control group (Sham, n=11), high CBDL group (model group, n=22) and blebbistatin treatment after high CBDL group (treatment group, n=22). The treatment group was intraperitoneally injected with blebbistatin at a dose of 5 mg/kg once a day for a week, while the model group was only given the solvent (PEG-300∶saline=1∶1). The changes of lung tissue were observed with HE staining. Western blotting was performed to detect the expression of myeloperoxidase (MPO), IL-6, TNF-α, and superoxide dismutase (SOD3) in the lung tissues. The expression levels of MPO, IL-6, IL-1β, TNF-α, LY6B, CD163, and vascular endothelium related factor CD31 were also determined by immunohistochemical assay.

The lung injury at the 3rd week after CBDL presented a large number of inflammatory cells infiltration, accompanied by local alveolar space and pulmonary interstitial hemorrhage. Immunohistochemical results demonstrated that the numbers of MPO positive cells, LY6B positive cells and CD163 positive cells were all increased significantly in the model group as compared with the Sham group (P<0.01), with enhanced expression of IL-1β and TNF-α (P<0.01). Western blotting results confirmed the up-regulated levels of MPO, IL-6 and SOD3 in the model group than the sham group (P<0.05). In comparison with the model group, the treatment group showed decreased numbers of MPO positive cells, LY6B positive cells, and CD163 positive cells (P<0.01), and declined levels of inflammatory factors IL-1β, IL-6, and TNF-α (P<0.01). Western blotting indicated as well that the expression of MPO, IL-6 and TNF-α in the treatment group was reduced greatly (P<0.05). Moreover, at the 5th week after surgery, the lung injury mainly manifested as pulmonary microvascular dilation, which was more severe in the model group than the Sham group (P<0.01), while the severity of pulmonary microvascular dilatation was remarkably milder after treatment (P<0.01).

Blebbistatin can effectively inhibit the infiltration of inflammatory cells in lung tissue, reduce pneumonia injury and alleviate pulmonary microvascular dilatation after CBDL.

To compare the analgesic effect and postoperative recovery quality of ultrasound-guided superficial and deep injection to superior costal transverse ligament (SCTL) for local anesthetics in thoracic paravertebral block (TPVB) combined with patient-controlled intravenous analgesia (PCIA) for postoperative analgesia in patients undergoing thoracoscopic surgery.

A total of 106 patients undergoing elective thoracoscopic surgery in the thoracic surgery department of our hospital from May 2021 to September 2021 were eligible for inclusion. They were randomly divided into SCTL superficial block group (Group S) and SCTL deep block group (Group T). Routine anesthesia induction and maintenance were performed in the both groups. After extubation, TPVB was operated under the guidance of ultrasound, and corresponding analgesic agent was injected into the superficial or deep surface of SCTL for local anesthetics, with 20 mL of 0.375% ropivacaine hydrochloride for single-point TPVB on the affected side, and PCIA was given at the same time. The positioning time and puncture time of ultrasonic image were recorded, the distance from the tip of ultrasonic image needle to pleura was measured, and the pleural depression and puncture related complications of ultrasonic image were observed. Visual analogue score (VAS) in resting and exercise (cough) states was evaluated at 5, 10, 20 and 30 min, and 4, 12 and 24 h (T_0~6) after block. The use of analgesic pump within 24 h after operation was observed in terms of sufentanil dosage, first compression time, effective compression times, and actual compression times. QOR-40 was employed to investigate the quality of recovery before and 24 h after operation.

Group S had significantly shorter puncture time (P<0.05) and longer distance from the tip of the needle to the pleura on ultrasound image when compared with Group T (P<0.05). Pleural depression could be observed in ultrasound image of 15 cases in Group S and of 51 cases in Group T (P<0.05). There was 1 case of epidural block in Group T. The VAS score at T₆ in exercise (cough) state was obviously higher in Group S than Group T (P<0.05). But, because the scores in both groups belonged to the range of mild pain score, no clinical difference was identified between the 2 groups. There were no statistical differences in the other VAS scores in resting and exercise (cough) states, time of image positioning under ultrasound guidance, and use of analgesic pump within 24 h after operation, and QOR-40 scores before and 24 h after operation between the 2 groups.

Both ultrasound-guided superficial and deep injection of analgesic drugs into SCTL for TPVB can provide effective postoperative analgesia and equivalent postoperative recovery quality for patients after thoracoscopic surgery. SCTL can be used as injection reference for ultrasound guidance. But the superficial injection of SCTL is safer, easier and simpler in operation.