Nonalcoholic fatty liver disease（NAFLD） is the most common chronic liver disease in the world. Because of its complex pathogenesis， high clinical prevalence and large population， it poses a great threat and challenge to public health in the world. Therefore， active intervention measures are needed. Currently， western medicine is effective in reducing weight， reducing liver fat content， improving glucose-lipid metabolism and insulin resistance. However， for patients with NAFLD-related fibrosis and cirrhosis， there is still a lack of sufficient histological evidence to support its benefits， and randomized controlled trials are still needed to clarify. Lifestyle intervention is an important cornerstone for the treatment of NAFLD， but there are many problems such as poor implementation and low compliance of patients， and the clinical efficacy is not ideal. Traditional Chinese medicine（TCM） has the significant advantages of multiple pathways and multiple targets. Berberine， the active ingredient of TCM， can interfere with the production of NAFLD from multiple pathways， including increasing energy consumption， weight loss， improving glucose-lipid metabolism， improving insulin resistance， anti-inflammatory， anti-oxidation， regulating intestinal flora， restoring bile acid homeostasis， anti-fibrosis and so on， which can play a positive role in the treatment of NAFLD. At the same time， it was found that the combination of BBR with Chinese and western medicines had significant advantages in promoting drug absorption， improving oral bioavailability， increasing the highest biological distribution in the liver， enhancing the overall therapeutic effect of NAFLD， and reducing adverse drug reactions， which could provide reference for clinical medication.

Acute lung injury （ALI） is a common and highly lethal clinical syndrome characterized by acute progressive respiratory failure. Currently， the treatment of ALI primarily involves respiratory support therapy and symptomatic pharmacotherapy， yet there is still a lack of specific and effective pharmacological treatments. Qingwen Baidu decoction is a traditional Chinese medicine formula that has the effects of clearing heat， removing toxin， cooling blood， and purging fire. Its pharmacological effects include anti-inflammatory， antipyretic， antibacterial， antiviral， sedative， and so on. The flavonoids， phenols， terpenes， and other components contained in this formula have strong pharmacological activity， which can regulate the inflammatory response caused and oxidative stress in ALI and maintain the integrity of alveolar-capillary barrier （ACB） by anti-apoptosis， anti-pathogen infection， and anti-pulmonary fibrosis， thereby improving the pathological changes of lung tissue. Among them， flavonoids have been reported more， and their mechanism of action is complex and diverse. For example， quercetin， luteolin， and baicalin act on multiple important targets， such as signal transducer and activator of transcription 3 （STAT3）， mitogen-activated protein kinase 3 （MAPK3）， etc. and participate in the regulation of Toll-like receptor 4 （TLR4）/myeloid differentiation primary response 88 （MyD88）/nuclear factor kappa B （NF-κB）， nuclear factor erythroid 2-related factor 2（Nrf2）/Kelch-like ECH-associated protein 1 （Keap1）， and silent information regulator 1 （SIRT1）/forkhead box protein O1 （FoxO1） signaling pathways， thereby intervening in pathological events such as inflammation， oxidative stress， cell apoptosis， and fibrosis. This paper aims to review the research progress on Qingwen Baidu decoction and its active ingredients in the prevention and treatment of lung injury in the expectation of providing reference for its subsequent pharmacological mechanism research and theoretical support for its clinical application and drug development in the treatment of ALI.

ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma， and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography（HPLC） was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces， and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside， chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics， the contents and quantity ratio relationships of the glycosides， aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed， and the partial least squares-discriminant analysis（PLS-DA） and cluster analysis of the main components in different steaming times were conducted， the statistically significant differential markers were selected with the variable importance in the projection（VIP） value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma， there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times， the anthraquinone glycosides and aglycones could be roughly divided into three stages， including rapid change stage， fluctuation change stage and stable stage， and the total amount of tannins showed a decreasing trend. However， the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes， while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening， it was found that chrysophanol， emodin， chrysophanol-8-O-β-D-glucoside， rhein， physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb， which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.

OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

OBJECTIVE To develop a prediction model for durable clinical benefit （DCB） in patients with advanced esophageal squamous cell carcinoma （ESCC） receiving programmed death-1 （PD-1） inhibitor. METHODS The clinical data of patients with advanced ESCC who received PD-1 inhibitor in Jieyang People’s Hospital were retrospectively collected between January 2020 to December 2023. Predictors were screened by least absolute shrinkage and selection operator （Lasso） regression， and a multivariable Logistic regression model was developed to predict DCB. A nomogram was constructed based on the model. Internal validation of the prediction model was performed by using the Bootstrap method， and the model was evaluated by the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis. RESULTS A total of 91 patients with advanced ESCC were included. The results of Lasso regression combined with Logistic regression analysis indicated that the baseline lymphocyte monocyte ratio （LMR） [odds ratio （OR）＝1.97， 95% confidence interval （CI）： 1.15-3.36， P＝0.013]， albumin （ALB） content （OR＝1.35， 95%CI： 1.13-1.60， P＜0.001）， body mass index （BMI） category 1 [normal vs. low： OR＝ 0.28， 95%CI （0.09-0.96）， P＝0.042]， BMI category 2 [overweight-obesity vs. low： OR＝0.08， 95%CI （0.01-0.59）， P＝0.013]， and treatment regimen [monotherapy vs. monotherapy combination therapy： OR＝0.07， 95%CI （0.01-0.50）， P＝0.008] were predictive factors for patients with advanced ESCC to achieve DCB when treated with PD-1 inhibitor. A prediction model was constructed based on the above indicators. Internal validation of the model using the Bootstrap method showed an area under the curve of 0.831 （95%CI： 0.746-0.904）， with specificity of 74.4% and sensitivity of 75.0%. The Hosmer-Lemeshow test yielded χ2＝ 9.930， P＝0.270， and the calibration curve slope was close to 1. The decision curve analysis demonstrated that the model exhibited good clinical utility within a threshold range of 0.1 to 1.0. CONCLUSIONS The prediction model based on baseline LMR， ALB content， BMI， and treatment regimen demonstrates robust predictive performance and clinical utility for assessing therapeutic efficacy of PD-1 inhibitor in the treatment of advanced ESCC.

OBJECTIVE To construct a risk prediction model for bloodstream infection （BSI） induced by carbapenem-resistant Klebsiella pneumoniae （CRKP）. METHODS Retrospective analysis was conducted for clinical data from 253 patients with BSI induced by K. pneumoniae in the First Hospital of Qinhuangdao from January 2019 to June 2022. Patients admitted from January 2019 to December 2021 were selected as the model group （n＝223）， and patients admitted from January 2022 to June 2022 were selected as the validation group （n＝30）. The model group was divided into the CRKP subgroup （n＝56） and the carbapenem- sensitive K. pneumoniae （CSKP） subgroup （n＝167） based on whether CRKP was detected or not. The univariate and multivariate Logistic analyses were performed on basic information such as gender， age and comorbid underlying diseases in two subgroups of patients； independent risk factors were screened for CRKP-induced BSI， and a risk prediction model was constructed. The established model was verified with patients in the validation group as the target. RESULTS Admissioning to intensive care unit （ICU）， use of immunosuppressants， empirical use of carbapenems and empirical use of antibiotics against Gram-positive coccus were independent risk factors of CRKP-induced BSI （ORs were 3.749， 3.074， 2.909， 9.419， 95%CIs were 1.639-8.572， 1.292- 7.312， 1.180-7.717， 2.877-30.840， P＜0.05）. Based on this， a risk prediction model was established with a P value of 0.365. The AUC of the receiver operating characteristic （ROC） curve of the model was 0.848 [95%CI （0.779， 0.916）， P＜0.001]， and the critical score was 6.5. In the validation group， the overall accuracy of the prediction under the model was 86.67%， and the AUC of ROC curve was 0.926 [95%CI （0.809， 1.000]， P＜0.001]. CONCLUSIONS Admission to ICU， use of immunosuppressants， empirical use of carbapenems and empirical use of antibiotics against Gram-positive coccus are independent risk factors of CRKP- induced BSI. The CRKP-induced BSI risk prediction model based on the above factors has good prediction accuracy.

Xenotransplantation is an efficient pathway to solve the problem of transplant organ source deficiency in clinical settings. With the increasing progress of gene editing technique and immune suppression regimen, important development has been achieved on researches regarding pig to non-human primate kidney xenotransplantation, which provides a good condition for the introduction of the technique in the clinical application. In view of the substantial difference between human and non-human primate, and to meet the needs of current ethic requirements, it is necessary to perform subclinical studies for pig to human kidney xenotransplantation. In recent years, such subclinical studies with regard to the genetically modified pig to brain death recipient kidney xenotransplantation had been performed, indicating that kidney xenotransplantation gradually began to transit to the clinical development stage. However, donor/recipient selection and immune suppression regimen has not reached a consensus yet, and has to be clarified in subclinical studies. In this article, the current status and confronted problems of donor/recipient selection, immune suppression regimen and post transplantation management in the subclinical studies of kidney xenotransplantation were reviewed, aiming to promote the clinical transformation of kidney xenotransplantation to the clinical application.

Positron emission tomography (PET) now plays an important role in the research and development (R&D) of central nervous system (CNS) drugs. PET could characterize the biodistribution, pharmacokinetics, and receptor binding of CNS drugs quantitatively. The present review summarized the quantitative methods of PET used in the pharmacokinetics and receptor occupancy analysis of CNS drugs. Moreover, the present review listed various applications of PET supporting R&D of CNS drugs, which could provide a new direction for the R&D of CNS drugs.