Organoid technology， a rapidly advancing three-dimensional （3D） cell culture platform， can closely mimic the microarchitecture and functions of human digestive organs， effectively overcoming the limitations of conventional two-dimensional cell models and animal experiments. By systematically summarizing the distinctive strengths of organoid technology in simulating digestive physiological and pathological states， constructing digestive system disease models， enabling high-throughput drug screening， and facilitating personalized treatment， this review explored the potential applications of organoids in identifying active components of traditional Chinese medicine （TCM） formulas， evaluating in vitro pharmacokinetics and toxicological parameters， and investigating multi-target synergistic mechanisms. By integrating cutting-edge engineering technologies， organoids are expected to provide a more scientific research platform for TCM， accelerate the modernization of its mechanistic studies， and enhance its scientific value and global impact.

ObjectiveTo analyse the current implementation status of Chinese herbal medicine （CHM） placebo and systematically evaluate the placebo effect in randomised controlled trials （RCTs） of traditional Chinese medicine （TCM） for the treatment of functional dyspepsia （FD）. MethodsA combination of medical subject terms and free words was used to search six databases， including PubMed， EMBASE， Cochrane Library， Web of Science， China National Knowledge Infrastructure， and Wanfang， for RCTs with CHM placebo group for FD published from January 31st， 1994 to September 30th， 2023. The dosage forms， composition， and methodological quality were collected and evaluated. The quality of the included articles was evaluated by Cochrane risk of bias assessment tool， and meta-analysis was performed on the CHM placebo response rate of patients with FD， and subgroup analysis and meta-regression was performed according to diagnostic criteria， efficacy criteria， duration of treatment， type of placebo， whether it contained active ingredient， and whether it evaluated placebo effects. ResultsA total of 34 publications were included involving 5046 participants， of which 2221 FD patients received CHM placebo treatment. Granules were the predominant placebo preparation， accounting for 71% （24/34）； 32.35% （11/34） of the studies added real CHM to the placebo， and only 12 （35%） of the studies described appearance， odour， and taste. The placebo response rate in FD patients in the placebo group was 41% （95% CI： 0.35 to 0.47； P＜0.01， I² = 87%）； there was significant difference between groups with different diagnostic criteria and different treatment durations （P＜0.05 or P＜0.01）， but there was no significant difference between the different efficacy evaluation criteria， the different placebo preparation， the presence of a low-dose active ingredient， and the presence or absence of placebo assessment （P＞0.05）. ConclusionThere was a significant CHM placebo effect in patients with FD， with granules as the main preparation of placebop. Different diagnostic criteria and different treatment times may affect the response rate of patients， and the addition of low-dose real medicine to the CHM placebos has not been seen to have an effect on the response rate. Clinical investigators have not paid enough attention to placebos， and there is a lack of uniform standards and norms for the preparation and evaluation of CHM placebos.

Spleen deficiency is an important part of the theoretical system of Traditional Chinese Medicine,which has experienced the process of origin,standardization,maturity,perfection and development in different historical periods.The physiological function of the spleen in Traditional Chinese Medicine involves"the spleen governs transportation and transformation,promotes blood circulation";The study of"spleen governing transportation and transformation"divided into"spleen governing transportation"and"spleen governing transformation"from the function of spleen,which is more conducive to explaining the scientific connotation of spleen governing transportation and transformation.Spleen governing transport and transformation is the basis of spleen governing clearing,and spleen governing clearing is the purpose of spleen governing transport and transformation.Spleen governing blood circulation is the outcome of spleen governing clearing,and there is a progressive logical hierarchy relationship between them.With the rise of proteomics,metabonomics and intestinal flora research,it provides technical support for the study of spleen deficiency syndrome;In addition,based on the correlation between spleen of Traditional Chinese Medicine and the functions of endoplasmic reticulum,the material basis of essence of spleen deficiency is discussed from the perspective of endoplasmic reticulum stress,which provides a new direction for the study of spleen deficiency.

Accurate segmentation of whole slide images is of great significance for the diagnosis of pancreatic cancer. However, developing an automatic model is challenging due to the complex content, limited samples, and high sample heterogeneity of pathological images. This paper presented a multi-tissue segmentation model for whole slide images of pancreatic cancer. We introduced an attention mechanism in building blocks, and designed a multi-task learning framework as well as proper auxiliary tasks to enhance model performance. The model was trained and tested with the pancreatic cancer pathological image dataset from Shanghai Changhai Hospital. And the data of TCGA, as an external independent validation cohort, was used for external validation. The F1 scores of the model exceeded 0.97 and 0.92 in the internal dataset and external dataset, respectively. Moreover, the generalization performance was also better than the baseline method significantly. These results demonstrate that the proposed model can accurately segment eight kinds of tissue regions in whole slide images of pancreatic cancer, which can provide reliable basis for clinical diagnosis.
Humans ; China ; Pancreatic Neoplasms/diagnostic imaging* ; Learning

Objective:The tumor-stroma ratio(TSR)is considered an independent prognostic factor for gastric cancer.Traditionally,TSR as-sessments have relied on the visual evaluation of surgical specimens,which is a method that lacks objectivity.This study was conducted to investigate whether the TSR in preoperative biopsy specimens can be automatically quantified using deep learning methods and whether the TSR value can be used to predict the efficacy of neoadjuvant chemotherapy(NAC)in patients with gastric cancer.Methods:In total,148 preoperative biopsy slides and 43 surgical resection slides from patients with gastric cancer who underwent NAC treatment at Yunnan Can-cer Hospital between March 2013 and March 2020 were used in the study.Tumor region segmentation and epithelial-stromal segmentation models were developed.The surgical resection slides were used to trained and evaluate the model,and the biopsy slides were used to test their predictive abilities.The TSR values were determined on the basis of the intersection of predictions from both models.The postoperat-ive pathological tumor regression grade(TRG)was used to categorize patients into good responders(TRG 0-1)and poor responders(TRG 2-3).Univariate and multivariate Logistic regression analyses were conducted to determine the correlation between the TSR value and the ef-ficacy of NAC in gastric cancer.Results:The intersection over union(IOU)value was 0.94 for the tumor tissue segmentation model and 0.88 for the epithelial-stromal segmentation model.Using cutoff values of 44.93％and 70.22％,patients were classified into low,intermediate,and high TSR groups.The proportion of good responders was significantly different among these groups(P＜0.05).Multivariate Logistic re-gression analysis indicated that the TSR was an independent predictor of NAC response in gastric cancer(OR=0.10,95％CI:0.03-0.32).When the TSR three-category classification was added as a predictor of treatment response alongside conventional clinical information,the area under curve(AUC)increased from 0.71 to 0.85.Conclusions:This deep learning model is capable of automatically segmenting tumor,epi-thelial,and stromal regions based on pathological slides,accurately calculating TSR value,and predicting the efficacy of NAC on the basis of the automatically computed TSR values.

OBJECTIVE To investigate the pharmacodynamic effects of the Citri Grandis Exocarpium extract on anorexia model immature rats.METHODS Ten immature rats were randomly selected as the control group and given regular diet， while anorexia model was induced in the remaining 50 immature rats using the etiological simulation method. The immature model rats were divided into the model group， Jianwei xiaoshi tablet group （0.65 g/kg）， Citri Grandis Exocarpium extract low-dose， medium- dose and high-dose groups （0.5， 1.0， 2.0 g/kg）. After 14 d of continuous intragastric administration， the body mass and food intake of rats in each group were observed， and the gastric acid concentration， pepsinase activity， serum levels of gastrin （GAS）， motilin （MTL） and gastric inhibitory peptide （GIP） were measured. The histopathological changes in the gastric tissue were observed.RESULTS Compared with control group， the food intake， gastric acid concentration， pepsin activity， the levels of GAS and MTL were significantly decreased and GIP level was significantly increased in the immature rats of model group （P＜0.05）； gastric histopathological examination showed significant gastric mucosal congestion and loosening and detachment of epithelial cells. Compared with model group， all administration groups showed different degrees of improvement in the above indexes and decreased gastric histopathological damage after drug intervention.CONCLUSIONS Citri Grandis Exocarpium extract improves gastric motility and protects gastric mucosa in the immature rats by regulating the concentration of gastric acid， pepsin activity， the levels of GAS， MTL and GIP， thus improving anorexia in immature rats.

OBJECTIVE To establish a method for the content determination of patulin in Citri Grandis Exocarpium. METHODS High-performance liquid chromatography-triple quadrupole mass spectrometer（HPLC-MS/MS）was used for the analysis. After water-soluble dispersion and pectinase enzymolysis， the Citri Grandis Exocarpium sample was extracted by acetonitrile with high-speed homogenated. The extracted solution was conducted dispersive solid phase extraction by mixing powder of MgSO4 and NaAC （4∶1，m/m），then purified on SHIMSEN 228 solid phase purification column. Water acetonitrile was used as mobile phase， and the Shim-pack XR-ODS column was used to separate the target compound. And it was detected by electrospray ionization in the negative mode under multiple reaction monitoring， and quantified by the external standard method with matrix- matched standard correction curves. RESULTS Patulin showed good linear correlation in the concentration from 5 to 200 ng/mL （r＝0.999 6）. RSDs of precision， reproducibility and stability tests （12 h） were all lower than 6％. The average recoveries at low， medium， high concentrations were 83.9%， 92.08%， 92.21%， respectively （RSDs were 11.09%， 5.53%， 1.75%， respectively）. The limit of quantitation was 6 μg/kg and limit of detection was 3 μg/kg. Patulin was not detected in 20 batches of samples. CONCLUSIONS Established method can be used for the rapid detection and accurate quantification of patulin in Citri Grandis Exocarpium， which can provide experimental basis and method for safety study and quality control of Citri Grandis Exocarpium.

ObjectiveTo explore the pharmacodynamic effect of the water extract of Citri Grandis exocarpium （WEC） on mice with alcohol-induced acute liver injury and provide data support for the development of this medicinal for anti-alcoholism and liver protection. MethodThe main components of WEC were determined by high performance liquid chromatography （HPLC）. Sixty Balb/c mice were randomized into 6 groups： control group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， model group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， low-， medium-， and high-dose WEC groups （0.5， 1.0， 2.0 g·kg^-1）， and Haiwang Jinzun tablet positive control group （2.0 g·kg^-1）. The administration lasted 14 days. One day before the end of the administration， mice were fasted for 12 h with free access to water. The mice， except the control group， were given 56° Chinese liquor （13 mL·kg^-1）. After 2 h， blood was taken from eyeballs and the liver was dissected and weighed. Automatic biochemical analyzer was employed to detect the expression of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and alcohol dehydrogenase （ADH）. The pathological changes of liver tissues were observed based on hematoxylin-eosin （HE） staining， and apoptosis of hepatocytes based on TUNEL/DAB staining. The expression of proteins related to apoptosis was detected by Western blot. ResultAccording to the HPLC fingerprint， the main components of WEC were rhoifolin and naringin. Compared with the control group， the model group showed increase in liver/body weight ratio （P<0.01） and the expression of ALT and AST （P<0.05， P<0.01）， decrease in the expression of ADH （P<0.05）， blurred structure of hepatic lobules， pathological changes of liver tissue， loose cytoplasm with edema， severe steatosis， rise of the TUNEL-positive rate （P<0.01）， reduction in expression of Bcl-2 （P<0.01）， and increase in Bax and Caspase-3 （P<0.01）. Compared with the model group， medium-dose WEC lowered liver/body weight ratio （P<0.05）. All doses of WEC depressed the activity of ALT and AST （P<0.05， P<0.01）， up-regulated the expression of ADH （P<0.05）， significantly improved the pathological features of alcohol-induced cytoplasmic porosity， edema， and steatosis， down-regulated the TUNEL-positive rate （P<0.05， P<0.01）， enhanced the expression of Bcl-2 （P<0.05）， and decreased Bax and Caspase-3 （P<0.01）. ConclusionWEC regulates the expression of ALT， AST， and ADH and improves hepatic steatosis and hepatocyte apoptosis to fight against acute liver injury.

OBJECTIVE：To optimize the microwave processing technology of yellow wine-processed Corydalis yanhusuo . METHODS：The contents of opioid alkaloid ，berberine hydrochloride and tetrahydropalmatine in C. yanhusuo processed with yellow wine were determined by HPLC. The contents of the extracts were determined by hot dipping method. Based on the single factor tests ，using the appearance of yellow wine-processed C. yanhusuo with microwave processing technology ，the contents of extract，opioid alkaloid ，berberine hydrochloride and tetrahydropalmatine as indexes ，with the amount of yellow wine ，wetting time，microwave power and microwaving time as factors ，the processing technology was optimized with orthogonal test combined with comprehensive weighted scoring method ，and then validated and compared with traditional yellow wine-processed C. yanhusuo . RESULTS：The linear ranges of opioid alkaloid ，berberine hydrochloride and tetrahydropalmatine were 0.100-1.500 μg（R2＝0.999 6）， 0.012-0.188 μg（R2＝0.999 5），0.050-0.750 μg（R2＝0.999 8）. RSDs of precision ，stability（12 h）and repeatability tests were all less than 2％ . The recoveries were 99.15％ -100.34％（RSD＝0.54％ ，n＝6），99.52％ -100.78％（RSD＝0.69％ ，n＝6）， 99.26％-99.79％（RSD＝0.28％，n＝6）. The optimum microwave processing technology included that the amount of yellow wine was 4 g（about 20％ of medicinal material amount ），microwave power was 40％，wetting time was 3 hour，processing time was 3 min. The results of three verification tests showed that the contents of extract ，opioid alkaloid ，berberine hydrochloride and tetrahydropalmatine were 15.7％-16.1％，0.061％-0.063％，0.003％-0.004％ and 0.061％-0.063％. The comprehensive scores were 97.916，94.730 and 97.217，and RSD were 0.42％，0.38％，0.46％（n＝3），respectively. Compared with traditional yellow wine processing technology ，there was no significant difference in the contents of opioid alkaloid and other components ，but no scorched spot and crumbs was found in yellow wine-processed C. yanhusuo with microwave processing technology. CONCLUSIONS：Established method for content determination is simple ，accurate，reliable and reproducible ，and can be used for quantitative analysis of active components in yellow wine-processed C. yanhusuo . Optimized microw ave processing technology is stable and feasible ，and can be used for the processing of yellow wine-processed C. yanhusuo .

Objective To investigate the value of neurite orientation dispersion and density imaging (NODDI) in quantitative evaluation of the microstructural changes in basal ganglia and thalamus in Wilson's disease (WD) patients,and to assess the diagnostic efficacy of NODDI.Methods Totally 27 WD patients (WD group) and 26 age-and sex-matched controls (control group) were enrolled.All subjects underwent MR scanning with NODDI.Parameters of NODDI,including intracellular volume fraction (Vic),orientation dispersion index (ODI) and isotropic volume fraction (Viso) of bilateral caudate nucleus,globus pallidus,putamen and thalamus were compared between the 2 groups.Correlation analysis was performed between each parameter of NODDI and clinical Young scores.Random Forest model was used to assess the relative importance of each parameter and to evaluate the diagnostic efficacy.Results The Vic and ODI of bilateral caudate nucleus,globus pallidus and putamen in WD patients were significantly lower than those in normal controls (all P＜0.05),while Viso was significantly higher than that in normal controls (all P＜0.05).The Vic of bilateral thalamus was lower,while Viso was higher in WD patients than those in normal controls (all P＜0.05),and ODI had no significant difference between the 2 groups (P=0.055).In WD patients,Vic and ODI of bilateral caudate nucleus,globus pallidus and putamen were negatively correlated with clinical Young scores.Viso of globus pallidus and putamen were positively correlated with clinical scores.The prediction accuracy of NODDI was 96.23％,and the area under ROC curve was 0.96.Conclusion NODDI can effectively evaluate changes in microstructures and metabolism during copper deposition in WD patients,and it may be useful in detecting changes of brain deep nuclei and assessing the progression of WD.