Immunotherapy, including immune checkpoint inhibitors, tumor vaccine therapy, oncolytic virotherapy, and adoptive cell therapy, has made remarkably breakthroughs in the field of oncology. Immune checkpoint inhibitors, which block programmed death receptor 1 or programmed death ligand 1, have been included in the first-line clinical treatment for advanced solid tumors, such as non-small cell lung cancer and malignant melanoma. However, primary or secondary drug resistance in tumors severely limits the survival benefits for patients. Immune-related adverse reactions, such as pneumonia, hypothyroidism, hypophysitis, and myocarditis, also greatly affect the quality of life of patients. Fuzheng Jiedu Huayu is an important concept guiding the prevention and treatment of tumors with traditional Chinese medicine (TCM). It is also a curative principle and therapeutic TCM method to reduce the toxicity and enhance the efficacy of immunotherapy. This article summarizes the research progress of immunotherapy and discusses how TCM reduces the toxicity and enhances the efficacy of immunotherapy, hoping to provide a reference for the integrated treatment of tumors with TCM and immunotherapy.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

Objective:To establish an animal model of trans-sutural distraction osteogenesis in SD rats.Methods:A self-designed V-shaped distraction device(distractor)was fabricated with the traction force(N)of 0,1.3,2.2,3.0,4.3 and 5.0 corresponding to the distraction length(mm)of 5,4,3,2,1 and 0 respectively,meeting the trans-sutural distraction osteogenesis requirements in skull of 5-week-old SD rats.The distractor was plased into the sagittal suture of 12 SD rats.Continuous sampling was conducted 1,3,5 and 7 days respectively(n=3)after operation.The tissue changes in the trans-sutural distraction area were observed by HE and Masson's trichrome staining.Inflammation levels were determined using Arg-1 immunofluorescence staining.The early angiogenesis was clarified through co-staining with CD31 and EMCN.Results:A stable trans-sutural distraction osteogenesis model was estab-lished,5 mm distraction osteogenesis width was observed completely within 7 days of distraction.Significant new bone formation was observed at 7 days after operation.Arg-1 expression increased and was concentrated at the bone margins,overlapping with the areas of new bone formation.EMCN expression gradually decreased,and by day 7 CD31 was predominant,indicating the basic maturation of blood vessels.Conclusion:This study successfully constructed a stable and effective trans-sutural distraction osteogenesis animal model,and provides an experimental basis for the investigation of its early continuous histological changes.

Objective To observe the value of radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced hepatobiliary phase(HBP)MRI for assessing clinical pathological stage of hepatic fibrosis(HF).Methods Data of 240 patients with pathologically/clinically diagnosed and clinical pathological staged HF who underwent Gd-EOB-DTPA enhanced MR examination were retrospectively analyzed.The liver-to-muscle signal intensity ratio(SIR1)and liver-to-spleen signal intensity ratio(SIR2)were measured based on HBP images.Radiomics features of HBP images were extracted and screened to construct radiomics models.The signal intensity ratio(SIR)-radiomics combined models were constructed based on SIR and radiomics signatures.Receiver operating characteristic(ROC)curves were drawn to evaluate the efficacy of each model for assessing clinical pathological stage of HF.Results The area under the curve(AUC)of SIR1 and SIR2 models for assessing clinical pathological stage of HF were 0.63-0.70 and 0.65-0.71,respectively.The most effective radiomics model for assessing HF,significant HF,advanced HF and early cirrhosis was support vector machine(SVM),SVM,light gradient boosting machine and K-nearest neighbor model,respectively,with the AUC in validation set of 0.87,0.82,0.81 and 0.80,respectively,while the AUC of SIR-radiomics combined models in validation set of 0.88,0.82,0.82 and 0.81,respectively.Conclusion The radiomics models based on Gd-EOB-DTPA enhanced HBP MRI were helpful for assessing clinical pathological stage of HF.Combining with HBP SIR could improve their efficacy.

ObjectiveTo investigate the value of aspartate aminotransferase-to-platelet ratio index （APRI） and platelet-albumin-bilirubin （PALBI） score in predicting the risk of esophagogastric variceal bleeding in patients with liver cirrhosis. MethodsA total of 119 patients with liver cirrhosis who were admitted to The First Affiliated Hospital of Soochow University from May 2021 and June 2022 were enrolled， and clinical data， routine blood test results， serum biochemistry， and coagulation test results were collected from all patients. According to the presence or absence of esophagogastric variceal bleeding， the patients were divided into non-bleeding group with 59 patients and bleeding group with 60 patients， and a comparative analysis was performed for the two groups. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-squared test or the Fisher’s exact test was used for comparison of categorical data between groups. The multivariate Logistic regression analysis was used to identify the independent risk factors for esophagogastric variceal bleeding in patients with liver cirrhosis and establish a nomogram predictive model. ResultsThe male patients accounted for 75.00% in the bleeding group and 40.68% in the non-bleeding group， and there was a significant difference in sex composition between the two groups （χ²=14.384， P<0.001）. Chronic hepatitis B was the main etiology in both the bleeding group and the non-bleeding group （53.33% vs 38.98%）， and there was no significant difference in composition ratio between the two groups （χ²=2.464， P=0.116）. Compared with the non-bleeding group， the bleeding group had a significantly higher activity of AT-IIIA （t=3.329， P=0.001） and significantly lower levels of PLT， TBil， Ca， TC， and TT （all P<0.05）. There were significant differences in APRI and PALBI between the two groups （χ²=6.175 and 19.532， both P<0.05）. The binary logistic regression analysis showed that APRI （odds ratio ［OR］=0.309， 95% confidence interval ［CI］： 0.109‍ ‍—‍ ‍0.881， P=0.028）， PALBI （OR=7.667， 95%CI： 2.005‍ ‍—‍ ‍29.327， P=0.003）， Ca （OR=0.001， 95%CI： 0.000‍ ‍—‍ ‍0.141， P=0.007）， TC （OR=0.469， 95%CI： 0.226‍ ‍—‍ ‍0.973， P=0.042）， and TT （OR=0.599， 95%CI： 0.433‍ ‍—‍ ‍0.830， P=0.002） were independent influencing factors for esophagogastric variceal bleeding in liver cirrhosis. A nomogram model was established based on the above factors and had an index of concordance of 0.899 and a well-fitted calibration curve. ConclusionAPRI and PALBI have a good value in predicting esophagogastric variceal bleeding in patients with liver cirrhosis， and the nomogram model established based on this study can predict the incidence rate of esophagogastric variceal bleeding in patients with liver cirrhosis.

Objective To compare the effect of routine speech training and computer-assisted training on post-stroke dysarthria. Methods From March,2021 to April,2023,72 patients with post-stroke dysarthria in Beijing Bo'ai Hospital were ran-domly divided into control group(n=36)and experimental group(n=36).Both groups received routine rehabili-tation,while the control group received routine speech training,and the experimental group received computer-assisted training,for four weeks.They were assessed with modified Frenchay Dysarthria Assessment(m-FDA)and Speech Intelligibility(SI)before and after intervention. Results Eight cases in the control group and one case in the experimental group dropped down.The scores of m-FDA and SI improved in both groups after treatment(|Z|＞4.183,P＜0.001),and there was no significant difference between two groups(|Z|＜1.598,P＞0.05).Noninferiority of m-FDA was found between two groups(|t|＞3.656,P＜0.001). Conclusion Computer-assisted training could improve the speech function of patients with post-stroke dysarthria,simi-lar to routine speech training.

Objective:To explore the regulatory effects of Danzhi Jiangtang Capsules on glucose metabolism and mitochondrial oxidative stress levels in db/db mice.Methods:Totally 32 db/db mice were randomly divided into model group, positive control group, and Danzhi Jiangtang Capsule low-, medium- and high-dosage groups; at the same time, 8 same-sex C57BL/6 mice of the same week age were selected as the blank group. The metformin group was filled with metformin solution 0.1 g/kg, and the Danzhi Jiangtang Capsule low-, medium- and high-dosage groups were injected with 0.99, 0.49 and 0.25 g/kg Danzhi Jiangtang Capsule solution respectively. The model group and the blank group received the same volume of physiological saline solution for the gavage, 1 time/d, continuous 12 weeks. The weight and fasting blood sugar (FBG) changes in each group of mice were detected; the serum insulin (FINS) level was detected by ELISA method and the insulin resistance index (HOMA-IR) was calculated; kits were used to detect the pancreatic tissue SOD and MDA levels of each group of mice; HE staining was used to observe pathological morphology of pancreatic tissue. Transmission electron microscopy was used to observe the ultrastructure of pancreatic mitochondria; Western blot method was used to detect the expressions of p-AMPK and AMPK proteins in pancreatic tissue.Results:Compared with the model group, after 8 or 12 weeks of drug administration, the weight of mice in the Danzhi Jiangtang Capsule high-dosage group decreased ( P<0.05 or P<0.01), and the level of FBG decreased ( P<0.01); FINS and HOMA-IR in the Danzhi Jiangtang Capsule high- and medium-dosage groups decreased ( P<0.01), the SOD activity in Danzhi Jiangtang Capsule high- medium- and low-dosage groups increased, and the level of MDA decreased ( P<0.01); the expressions of p-AMPK and AMPK in Danzhi Jiangtang Capsule high-and medium-dosage groups increased ( P<0.01), the expression of AMPK in Danzhi Jiangtang Capsule low-dosage group increased ( P<0.01). Conclusion:Danzhi Jiangtang Capsule can improve SOD activity in pancreatic tissue of db/db mice, reduce MDA content, and activate the AMPK signaling pathway, suggesting that Danzhi Jiangtang Capsule can improve insulin resistance and restore glucose homeostasis by inhibiting oxidative stress levels and improving mitochondrial function.

The mutual recognition of medical examination results is significant for improving the utilization efficiency of limited resources in large public hospitals,promoting the sharing of quality medical resources,alleviating the high costs and diffi-culties of healthcare for the public,reducing pressure on medical insurance funds,and enhancing the efficiency of fund utiliza-tion.This study reviews the research on mutual recognition of medical examination results in China,analyzing it from four as-pects:regulatory norms,platform construction,policy awareness,and performance distribution.It identifies research hotspots and directions related to mutual recognition,clarifies the challenges and key points in the implementation of relevant policies,and suggests future research directions,including strengthening theoretical research,improving empirical studies,and innovating re-search methods.

Objective:To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism.Methods:Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue.Results:After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and severe damage to the tight junction complex structure of intestinal epithelial cells, which was significantly improved in the Ber group but less improved in the DAPT group. The levels of serum DAO, iFABP, TNF-α, IL-6 in the LPS group were significantly higher than those in the Sham group, while the above indicators in the Ber group were significantly lower than those in the LPS group [DAO (μg/L): 4.94±0.44 vs. 6.53±0.49, iFABP (ng/L): 709.67±176.97 vs. 1 417.71±431.44, TNF-α (ng/L): 74.70±8.15 vs. 110.36±3.51, IL-6 (ng/L): 77.34±9.80 vs. 101.65±6.92, all P < 0.01], while the above indicators in the DAPT group were significantly higher than those in the Ber group. The results of RT-PCR and Western blotting showed that the mRNA and protein expressions of Occludin, Claudin1, Notch1, and Hes1 in the ileum tissue of LPS group rats were decreased compared to the Sham group, which were significantly increased in the Ber group compared with the LPS group [mRNA expression: Occludin mRNA (2 -ΔΔCt): 1.61±0.74 vs. 0.30±0.12, Claudin1 mRNA (2 -ΔΔCt): 1.97±0.37 vs. 0.58±0.14, Notch1 mRNA (2 -ΔΔCt): 1.29±0.29 vs. 0.36±0.10, Hes1 mRNA (2 -ΔΔCt): 1.22±0.39 vs. 0.27±0.04; protein expression: Occludin/GAPDH: 1.17±0.14 vs. 0.74±0.04, Claudin1/GAPDH: 1.14±0.06 vs. 0.58±0.10, Notch1/GAPDH: 0.87±0.11 vs. 0.56±0.09, Hes1/GAPDH: 1.02±0.13 vs. 0.62±0.01; all P < 0.05], while those in the DAPT group were significantly lower than those in the Ber group. Conclusion:Early use of berberine hydrochloride can significantly improve intestinal mucosal barrier damage in sepsis rats, and its mechanism may be related to inhibiting inflammatory response and regulating the expression of intestinal mechanical barrier tight junction protein through Notch1 signal.