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.

Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.
Humans ; Glioma/metabolism* ; Blood Platelets/physiology* ; Brain Neoplasms/pathology* ; Tumor Microenvironment

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

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.

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 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 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.