Based on the theory of diseased collaterals and the progression pattern of diabetic kidney disease （DKD）， this paper proposes a staged treatment system based on the "three states of kidney collaterals" including collateral distention， collateral bi （痹） and collateral accumulation. In the collateral distention stage， the primary pathogenesis is heat damaging the kidney collaterals and collateral vessel dilation， corresponding to the early state of DKD characterized by hyperfiltration and microalbuminuria； the clearing method is suggested， and Shenling Jiangtang Formula （参苓降糖方） can be used to promote the remission of proteinuria by ameliorating insulin resistance and regulating intestinal microecology. In the collateral bi stage， the core pathogenesis lies in the binding of phlegm and stasis， and the formation of concretions and conglomerations in the kidney collaterals， corresponding to massive proteinuria and the decline of renal function， for which the unblocking method should be taken， using Jinchan Yishen Tongluo Formula （金蝉益肾通络方） and Qingre Xiaozheng Formula （清热消癥方） to alleviate renal pathological damage by regulating the autophagy-lysosome pathway and repairing mitochondrial energy metabolism. The collateral accumulation stage is characterized by the internal retention of turbid toxins and accumulations of concretions in the kidney collaterals， corresponding to renal fibrosis and end-stage renal disease （ESRD）； the dispersion method is suggested， and Yiqi Tongluo Xiezhuo Formula （益气通络泄浊方） and Shenyan Fangshuai Fluid （肾炎防衰液） can be used to inhibit extracellular matrix accumulation and delay the progressive loss of renal function. Collateral deficiency runs through the entire course of the disease and is closely related to cellular senescence and the imbalance of the ubiquitin-proteasome/autophagy system. The concept of the "three states of kidney collaterals" integrates the evolution of traditional Chinese medicine pathogenesis with modern pathological staging， forming a whole-course intervention system of "staging-syndrome differentiation-target-formula"， thereby providing novel insights for prevention and treatment of DKD using integrated traditional Chinese and western medicine.

T cell factor 1（TCF-1）is a downstream transcription factor of the Wnt/β-catenin signaling pathway，and plays an important role in the development，differentiation，and memory formation of T cells. Recent studies have shown that TCF-1 can regulate the formation and maintenance of stem-like memory T cells（Tscm），and has potential application value in evaluating the prognosis of tumor immunotherapy and as a target for tumor immunotherapy. This article reviews the regulatory effects of TCF-1 on the immune memory as well as stemness formation and maintenance of CD8 +T cells，summarizes the transcription network centered on TCF-1，and further elucidates the application and value of TCF-1 in tumor immunotherapy.

BACKGROUND:Buqi Huoxue Compounds have shown significant clinical effects on the treatment of ischemic stroke due to qi deficiency and phlegm stasis,but its specific mechanism of action needs to be further clarified.OBJECTIVE:To observe the effects of Buqi Huoxue Compounds on the neurological function,p-Akt and serum exosome expression in a rat model of cerebral ischemia-reperfusion injury.METHODS:Forty adult male SPF Sprague-Dawley rats,6 weeks old,were randomly divided into sham operation group,model group,Buqi Huoxue Compounds group,Buqi Huoxue Compounds+GW4869 group,with 10 rats in each group.In the latter three groups,a rat model of cerebral ischemia-reperfusion injury was established using thread technique.The sham operation group was given incision and separation without inserting a suture.The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion;the GW4869+Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion and intraperitoneally given GW4869[2.5 mg/(kg·d)]2 hours before gavage with 3 days after modeling.Both the sham operation group and model group received equal amounts of saline via gavage,three times a day,for 7 consecutive days.Neurological function,cerebral infarct volume,brain tissue morphology,characterization of serum exosome,p-Akt in the cortical area and CD63 and TSG101 in serum exosome were detected after 7 days of administration.RESULTS AND CONCLUSION:(1)After modeling,compared with the sham operation group,the neurological function scores of the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group were significantly increased(P＜0.01 or P＜0.05).After 7 days of intervention,the neurological function scores of the Buqi Huoxue Compounds group were significantly lower than those of the model group and Buqi Huoxue Compounds+GW4869 group(all P＜0.01).(2)The results of 2,3,5-triphenyltetrazolium chloride staining showed that cerebral infarct foci were observed in the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group,and the cerebral infarct volume in the Buqi Huoxue Compounds group was smaller than that in the model group and the Buqi Huoxue Compounds+GW4869 group(P＜0.01).(3)The results of hematoxylin-eosin staining showed that the morphological and structural abnormalities of nerve cells in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group were less severe than those in the model group,but some cells still exhibited cytoplasmic agglutination and pyknosis in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group.(4)NanoSight analysis showed that the diameters of the isolated particles ranged from 60 nm to 300 nm,consistent with the characteristic size of exosomes.(5)Western blot results showed that the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly lower in the model group compared with the sham operation group(P＜0.05 or P＜0.01).Compared with the model group,the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly higher in the Buqi Huoxue Compounds group than in the model group(P＜0.05 or P＜0.01).However,the p-Akt expression in the infarct zone and CD63 expression in serum exosomes decreased significantly in the Buqi Huoxue Compounds+GW4869 group(P＜0.05),while TSG101 expression decreased without significant difference after the addition of GW4869.(6)To conclude,Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury and increase the expression of p-Akt in rats by promoting exosome secretion.

T cell factor 1（TCF-1）is a downstream transcription factor of the Wnt/β-catenin signaling pathway，and plays an important role in the development，differentiation，and memory formation of T cells. Recent studies have shown that TCF-1 can regulate the formation and maintenance of stem-like memory T cells（Tscm），and has potential application value in evaluating the prognosis of tumor immunotherapy and as a target for tumor immunotherapy. This article reviews the regulatory effects of TCF-1 on the immune memory as well as stemness formation and maintenance of CD8 +T cells，summarizes the transcription network centered on TCF-1，and further elucidates the application and value of TCF-1 in tumor immunotherapy.

Shengyutang is a famous classical formula of tonic， which is made from Siwutang with Ginseng Radix et Rhizoma and Astragali Radix. It is included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. Based on the Principles of Key Information Research of Ancient Famous Classical Formulas， this paper used bibliometrics to sort out and research the key information of Shengyutang in the aspects of history， composition， origin and processing， dosage， decocting method， efficacy and indications. After research， it has been found that this formula was first recorded in Lanshi Micang written by LI Dongyuan during the Jin dynasty， composed of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix and Angelicae Sinensis taproot. The name of the formula passed down through generations was relatively unified， with clear origins and veins. In later generations， this formula was the mainstream， and adjustments were made to the dosage and composition according to the indication. In the formula， Astragalus membranaceus var. mongholicus was selected as the origin of Astragali Radix， and the origins of other medicinal materials were consistent with the 2020 edition of Chinese Pharmacopoeia. Except for Rehmanniae Radix Praeparata， the other medicinal materials were made from raw products， and the dosage form was boiled powder. According to the measurement standard in the Jin dynasty， the recommended usage and dosage were 1.24 g of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma each， 2.07 g of Astragali Radix and Angelicae Sinensis taproot each， crushed into coarse particles that pass through the 4 mesh sieve but can't pass through the 10 mesh sieve， added 1 200 mL of water and boiled to 300 mL， and removed the residue. Shengyutang has the functions of tonifying Qi and blood， and blood intake， treating various sores， and restlessness and insomnia caused by excessive blood flow. In ancient times， this formula was widely used in the treatment of surgical sores， gynecological diseases， deficiency syndrome， etc. In modern clinical practice， it is mostly used to treat gynecological， neurological， musculoskeletal， hematological diseases caused by Qi and blood deficiency. In this paper， the key information of Shengyutang was researched by reviewing relevant ancient literature， in order to provide reference for the modern application and development of this formula.

BACKGROUND:Buqi Huoxue Compounds have shown significant clinical effects on the treatment of ischemic stroke due to qi deficiency and phlegm stasis,but its specific mechanism of action needs to be further clarified.OBJECTIVE:To observe the effects of Buqi Huoxue Compounds on the neurological function,p-Akt and serum exosome expression in a rat model of cerebral ischemia-reperfusion injury.METHODS:Forty adult male SPF Sprague-Dawley rats,6 weeks old,were randomly divided into sham operation group,model group,Buqi Huoxue Compounds group,Buqi Huoxue Compounds+GW4869 group,with 10 rats in each group.In the latter three groups,a rat model of cerebral ischemia-reperfusion injury was established using thread technique.The sham operation group was given incision and separation without inserting a suture.The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion;the GW4869+Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion and intraperitoneally given GW4869[2.5 mg/(kg·d)]2 hours before gavage with 3 days after modeling.Both the sham operation group and model group received equal amounts of saline via gavage,three times a day,for 7 consecutive days.Neurological function,cerebral infarct volume,brain tissue morphology,characterization of serum exosome,p-Akt in the cortical area and CD63 and TSG101 in serum exosome were detected after 7 days of administration.RESULTS AND CONCLUSION:(1)After modeling,compared with the sham operation group,the neurological function scores of the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group were significantly increased(P＜0.01 or P＜0.05).After 7 days of intervention,the neurological function scores of the Buqi Huoxue Compounds group were significantly lower than those of the model group and Buqi Huoxue Compounds+GW4869 group(all P＜0.01).(2)The results of 2,3,5-triphenyltetrazolium chloride staining showed that cerebral infarct foci were observed in the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group,and the cerebral infarct volume in the Buqi Huoxue Compounds group was smaller than that in the model group and the Buqi Huoxue Compounds+GW4869 group(P＜0.01).(3)The results of hematoxylin-eosin staining showed that the morphological and structural abnormalities of nerve cells in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group were less severe than those in the model group,but some cells still exhibited cytoplasmic agglutination and pyknosis in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group.(4)NanoSight analysis showed that the diameters of the isolated particles ranged from 60 nm to 300 nm,consistent with the characteristic size of exosomes.(5)Western blot results showed that the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly lower in the model group compared with the sham operation group(P＜0.05 or P＜0.01).Compared with the model group,the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly higher in the Buqi Huoxue Compounds group than in the model group(P＜0.05 or P＜0.01).However,the p-Akt expression in the infarct zone and CD63 expression in serum exosomes decreased significantly in the Buqi Huoxue Compounds+GW4869 group(P＜0.05),while TSG101 expression decreased without significant difference after the addition of GW4869.(6)To conclude,Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury and increase the expression of p-Akt in rats by promoting exosome secretion.

Objective To observe the value of ultrasonic parameters for predicting whether patients with cesarean scar pregnancy(CSP)would benefit from ultrasound-guided suction curettage alone.Methods Totally 140 CSP patients diagnosed by transvaginal ultrasound and initially treated with ultrasound-guided suction curettage alone were prospectively recruited and categorized into benefited group(n=103)and non-benefited group(n=37)according to bleeding during suction curettage and prognoses.The ultrasonic manifestations of CSP were observed,and the thickness of chorionic villi at the scar,as well as of residual myometrium of the anterior wall in the lower segment of the uterus,also the maximum diameter of the gestational sac were measured and compared between groups,and the parameters with quantitative data being statistically different between groups were converted into categorical predictor through analyzing of the receiver operating characteristic(ROC)curves and the optimal cut-off values.The independent predictors were selected among ultrasonic features and categorical predictor variables being statistically different between groups using multivariate logistic regression,and a combined predicting model was then constructed,and the predicting efficacy of the combined model and each categorical predictor alone was assessed according to the area under curve(AUC)and then were compared.Results Compared with non-benefited group,the gestational weeks in benefited group were smaller(P＜0.05),and the percentages of rich blood supply and the presence of embryos and fetal heartbeats were lower,with thinner chorionic villi at the scar,thicker residual myometrium and smaller maximal diameter of the gestational sac in benefited group(all P＜0.05).ROC curves analyses yielded the best cut-off value for dichotomy of chorionic villi thickness at the scar was 4.7 mm,of residual myometrium thickness was 1.8 mm and of the maximum diameter of the gestational sac was 29 mm,respectively,and then categorical predictor variable were obtained.Multivariate logistic regression showed that the transformed categorical predictors,i.e.the thickness degree of the chorionic villi at the scar,the thickness degree of the residual muscle layer and the size degree of the gestational sac,were all independent predictors of whether CSP patients would benefit from ultrasound-guided suction curettage alone(all P＜0.05).The AUC of the combined predicting model was 0.918,higher than that of each transformed categorical predictor alone(all P＜0.05).Conclusion The thickness of the chorionic villi at the scar ≤4.7 mm,the thickness of the residual muscle layer＞1.8 mm and the maximum diameter of the gestational sac≤29 mm were all independent predictors of CSP patients would benefit from ultrasound-guided suction curettage alone,and the predicting efficacy of the combined model was higher than that of each alone.

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

Objective To preliminarily analyze the prediction efficiency of multimodal MRI?based radiomics model for preoperative glioma IDH1 gene expression type. Methods The MRI data of 108 surgery?proven glioma patients from May 2015 to January 2019 were retrospectively analyzed, and the MRI data included axial T1WI,T2WI,fluid attenuated inversion recovery (FLAIR),DWI imaging and enhanced T1WI sequence.Forty-seven cases were IDH1 mutant type, and 61 cases were IDH1 wild type. All patients were divided into training and validation groups according to the 7∶3 ratio of the random forest model. Seventy-three cases were in training group, and 35 cases were in validation group. Independent predictors of IDH1 mutation were screened by univariate analysis combined with multivariate logistic regression analysis (P<0.05) in order to construct a random forest diagnosis model of general clinical information and conventional MRI morphological features.General clinical information and conventional MRI morphological features included gender, age, umbers of cases of left and right hemispheres, location of tumors, maximum diameter of tumors, peritumoral edema, intratumoral cystic degeneration, enhancement and ADC value of tumors. The ROI was manually outlined by MaZda software in the most obvious level of 5 sequences of tumor mass and the radiomics features were extracted, including the gray?level co?occurrence matrix(GLCM), the run?length matrix(RUN), the absolute gradient(GRA),the auto?regressive model(ARM) and wavelets transform (WAV). The least absolute shrinkage and selection operator (LASSO)regression were used to select image radiomics features with a method of 10 fold cross?validation and to reduce the dimensions. The screened image radiomics labels were combined with the conventional morphological feature independent predictors to construct a multimodal MRI?based random forest model, and the validation data set was used to evaluate the accuracy and diagnostic efficiency of each model. The sensitivity and specificity of conventional MRI morphological feature model and multimodal MRI?based radiomics prediction model were evaluated dynamically by drawing ROC curves, and the prediction efficiency of the two models was quantified by using AUC statistical indicators. The model classification error rate under different outcomes and the classification error rate of out of bag(OOB)were used to evaluate the stability of the multimodal MRI?based random forest model. The contribution rate of each variable to the model was reflected by the characteristic variables importance assessment map. Results Univariate regression analysis of the conventional MRI morphological characteristics showed that peritumoral edema, cystic degeneration and enhancement were the three independent predictors of IDH1 gene expression (P<0.01). LASSO algorithm and 10?fold cross?validation identified six robust radiomic features including high frequency coefficients of wavelet transform (WavEnHH_s?4) of T2WI, S(4, 4) inverse difference of gray uniformity measurement (InvDfMom), S(5, 0) Entropy (entropy), WavEnHH_s?4 of T1WI enhancement, S(1, 1) InvDfMom, S(1, -1) Entropy Difference (DifEntrp)of Flair.The error rate of classification for different outcomes and classification error rate of random forest OOB data of multimodal MRI radiomics diagnosis model finally stabilized at 10%. The results of Characteristic Variable Importance Assessment Map: Mean Decrease Accuracy and Mean Decrease Gini index were consistent, which showed that besides three conventional MRI morphological predictors peritumoral edema, enhancement and cystic degeneration, the radiomics labels also played a key role in the model. The results of ROC curve showed that the accuracy, specificity,sensitivity and AUC of conventional MRI morphological feature model were 82.7%, 68.4%, 90.9% and 0.835, respectively, and those of multimodal MRI?based radiomics model were 88.5%, 89.5%, 87.8% and 0.956 respectively. Conclusion Multimodal MRI?based radiomics random forest model can improve the predictive efficiency of preoperative glioma IDH1 gene expression type more quantitatively.

Objective: To preliminarily analyze the prediction efficiency of multimodal MRI-based radiomics model for preoperative glioma IDH1 gene expression type. Methods: The MRI data of 108 surgery-proven glioma patients from May 2015 to January 2019 were retrospectively analyzed, and the MRI data included axial T₁WI,T₂WI,fluid attenuated inversion recovery (FLAIR),DWI imaging and enhanced T₁WI sequence.Forty-seven cases were IDH1 mutant type, and 61 cases were IDH1 wild type. All patients were divided into training and validation groups according to the 7∶3 ratio of the random forest model. Seventy-three cases were in training group, and 35 cases were in validation group. Independent predictors of IDH1 mutation were screened by univariate analysis combined with multivariate logistic regression analysis (P<0.05) in order to construct a random forest diagnosis model of general clinical information and conventional MRI morphological features.General clinical information and conventional MRI morphological features included gender, age, umbers of cases of left and right hemispheres, location of tumors, maximum diameter of tumors, peritumoral edema, intratumoral cystic degeneration, enhancement and ADC value of tumors. The ROI was manually outlined by MaZda software in the most obvious level of 5 sequences of tumor mass and the radiomics features were extracted, including the gray-level co-occurrence matrix(GLCM), the run-length matrix(RUN), the absolute gradient(GRA),the auto-regressive model(ARM) and wavelets transform(WAV). The least absolute shrinkage and selection operator (LASSO)regression were used to select image radiomics features with a method of 10 fold cross -validation and to reduce the dimensions. The screened image radiomics labels were combined with the conventional morphological feature independent predictors to construct a multimodal MRI-based random forest model, and the validation data set was used to evaluate the accuracy and diagnostic efficiency of each model. The sensitivity and specificity of conventional MRI morphological feature model and multimodal MRI-based radiomics prediction model were evaluated dynamically by drawing ROC curves, and the prediction efficiency of the two models was quantified by using AUC statistical indicators. The model classification error rate under different outcomes and the classification error rate of out of bag(OOB)were used to evaluate the stability of the multimodal MRI-based random forest model. The contribution rate of each variable to the model was reflected by the characteristic variables importance assessment map. Results: Univariate regression analysis of the conventional MRI morphological characteristics showed that peritumoral edema, cystic degeneration and enhancement were the three independent predictors of IDH1 gene expression (P<0.01). LASSO algorithm and 10-fold cross-validation identified six robust radiomic features including high frequency coefficients of wavelet transform (WavEnHH_s-4) of T₂WI, S(4,4) inverse difference of gray uniformity measurement (InvDfMom),S(5,0) Entropy (entropy),WavEnHH_s-4 of T₁WI enhancement, S(1,1) InvDfMom,S(1, -1) Entropy Difference (DifEntrp)of Flair.The error rate of classification for different outcomes and classification error rate of random forest OOB data of multimodal MRI radiomics diagnosis model finally stabilized at 10%. The results of Characteristic Variable Importance Assessment Map: Mean Decrease Accuracy and Mean Decrease Gini index were consistent, which showed that besides three conventional MRI morphological predictors peritumoral edema, enhancement and cystic degeneration, the radiomics labels also played a key role in the model. The results of ROC curve showed that the accuracy, specificity, sensitivity and AUC of conventional MRI morphological feature model were 82.7%, 68.4%, 90.9% and 0.835, respectively, and those of multimodal MRI-based radiomics model were 88.5%, 89.5%, 87.8% and 0.956 respectively. Conclusion Multimodal MRI-based radiomics random forest model can improve the predictive efficiency of preoperative glioma IDH1 gene expression type more quantitatively.