To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Virus-induced senescence (VIS) is a significant biological phenomenon, which is associated with declining immune function, accelerating aging process and causing aging-related diseases. A variety of common viruses, including RNA viruses (such as SARS-CoV-2), DNA viruses (such as herpesviruses and hepatitis B virus), and prions can cause VIS in host cells. The primary mechanisms include abnormal activation of the cGAS-STING signaling pathway, DNA damage response, and potential correlations with the integrated stress response due to intracellular phase separation. Viral infection and cellular senescence influence each other: cellular senescence serves as a defense to restrict viral replication and transmission, while some viruses exploit cellular senescence to enhance their infectivity and replication. Understanding the mechanisms of VIS is conducive to the development of therapeutic strategies for viral infections and promotion of healthy aging. However, there is lack of research on therapeutic targets and drug development in this field so far. Although senolytics may be effective for anti-senescent cells therapy, their efficacy for VIS needs evidence from further clinical trials. This article reviews the research progress on the connection between viral infection and cellular senescence, to provide insights for the prevention and treatment of aging related diseases.
Humans ; Cellular Senescence/physiology* ; Virus Diseases/physiopathology* ; Signal Transduction ; Nucleotidyltransferases/metabolism* ; DNA Damage ; Virus Replication ; COVID-19 ; Membrane Proteins/metabolism* ; SARS-CoV-2

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

ObjectiveBased on cyclic adenosine monophosphate （cAMP）/cAMP-regulated guanine nucleotide exchange factor 1 （Epac1）/Ras-homologous protein 1 （Rap1） signaling pathway to explore the myocardial protective mechanism of Yiqi Huoxue prescription on coronary heart disease （CHD） rats with Qi deficiency and blood stasis syndrome. MethodEighty-eight specific-pathogen-free （SPF） grade male Sprague-Dawley （SD） rats were divided into a sham operation group （n=12） and an experimental group （n=76） according to the random number table. The experimental group underwent a restricted diet and exhaustive swimming combined with left anterior descending （LAD） coronary artery ligation to construct a model of CHD with Qi deficiency and blood stasis syndrome， and electrocardiograms （ECGs） of rats before and after the LAD operation were collected. After the model was successfully established， the rats were randomly divided into model group， Yiqi Huoxue prescription low-dose group （4.28 g·kg^-1）， medium-dose group （8.55 g·kg^-1）， high-dose group （17.1 g·kg^-1）， and Western medicine group （isosorbide mononitrate tablets， 3.6 mg·kg^-1）. Rats were intragastrically administered assigned drugs for 4 weeks consecutively， while the sham operation group and the model group were administered with equal volumes of double distilled water. Twenty-four hours after the final administration， the rats were anesthetized with isoflurane to detect the left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， left ventricular fractional shortening （FS， %）， and ejection fraction （EF， %） by echocardiography. Blood samples were collected from the abdominal aorta for hemorheological measurements， and plasma cAMP levels were determined using enzyme-linked immunosorbent assay （ELISA）. Myocardial tissue was collected for hematoxylin-eosin （HE） staining and Masson staining to observe myocardial pathological damage， and a transmission electron microscope was used to observe ultrastructural changes of myocardial tissue， fluorescent quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the expressions of myocardial Epac1， Rap1 GTPase activating protein （Rap1GAP） and Rap1 mRNA， and Western blot was used to detect the expressions of myocardial Epac1， Rap1GAP and Rap1 protein. ResultCompared with those in the sham operation group， LVEDD and LVISD of rats in the model group significantly increased （P<0.01）， and the ratios of EF and FS significantly decreased （P<0.01）， indicating symptoms of heart function decline， referred to as "heart Qi deficiency". The viscosity of whole blood and plasma significantly increased （P<0.01）， and the content of cAMP significant increased （P<0.01）. In addition， there was a significant proliferation of collagen fibers in myocardial tissue （P<0.01）， and the ultrastructure of the myocardial tissue was severely damaged， indicating pathological changes consistent with "blood stasis". Real-time PCR results showed that Epac1 and Rap1 mRNA levels in the model group were significantly reduced （P<0.01）， while Rap1GAP mRNA levels were significantly increased （P<0.01）. Western blot analysis showed a significant decrease in Epac1 protein expression （P<0.01） and a significant increase in Rap1GAP protein expression （P<0.05）. Compared with the model group， Yiqi Huoxue prescription improved cardiac function， reduced blood viscosity， lowered plasma cAMP levels， decreased collagen fiber proliferation， and improved myocardial ultrastructure damage in CHD rats with Qi deficiency and blood stasis syndrome. The high-dose group showed the most significant effects. In the high-dose group， Epac1 mRNA and protein expression levels significantly increased （P<0.01）， Rap1 mRNA expression significantly increased （P<0.01）， and Rap1GAP mRNA and Rap1GAP/Rap1 protein expression levels significantly decreased （P<0.05， P<0.01）. ConclusionYiqi Huoxue prescription can improve cardiac function， reduce blood viscosity and plasma cAMP levels， improve myocardial damage， and reduce collagen fiber proliferation in CHD rats with Qi deficiency and blood stasis syndrome. The myocardial protection mechanism may be related to the regulation of the cAMP/Epac1/Rap1 signaling pathway.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Objective:To construct a machine-learning model for predicting the progression of pancreatic cystic lesions (PCLs) based on clinical and CT features, and to evaluate its predictive performance in internal/external testing cohorts.Methods:Baseline clinical and radiological data of 200 PCLs in 177 patients undergoing abdominal thin slice enhanced CT examination at Peking Union Medical College Hospital from July 2014 to December 2022 were retrospectively collected. PCLs were divided into progressive and non-progressive groups according to whether the signs indicated for surgery by the guidelines of the European study group on PCLs were present during three-year follow-up. 200 PCLs were randomly divided into training (150 PCLs) and internal testing cohorts (50 PCLs) at the ratio of 1∶3. 15 PCLs in 14 patients at Jinling Affiliated Hospital of Medical School of Nanjing University from October 2011 to May 2020 were enrolled as external testing cohort. The clinical and CT radiological features were recorded. Multiple feature selection methods and machine-learning models were implemented and combined to identify the optimal machine-learning model based on the 10-fold cross-validation method. Receiver operating characteristics (ROC) curve was drawn and area under curve (AUC) was calculated. The model with the highest AUC was determined as the optimal model. The optimal model's predictive performance was evaluated on testing cohort by calculating AUC, sensitivity, specificity and accuracy. Permutation importance was used to assess the importance of optimal model features. Calibration curves of the optimal model were established to evaluate the model's clinical applicability by Hosmer-Lemeshow test.Results:In training and internal testing cohorts, the progressive and non-progressive groups were significantly different on history of pancreatitis, lesions size, main pancreatic duct diameter and dilation, thick cyst wall, presence of septation and thick septation (all P value <0.05) In internal testing cohort, the two groups were significantly different on gender, lesion calcification and pancreatic atrophy (all P value <0.05). In external testing cohort, the two groups were significantly different on lesions size and pancreatic duct dilation (both P<0.05). The support vector machine (SVM) model based on five features selected by F test (lesion size, thick cyst wall, history of pancreatitis, main pancreatic duct diameter and dilation) achieved the highest AUC of 0.899 during cross-validation. SVM model for predicting the progression of PCLs demonstrated an AUC of 0.909, sensitivity of 82.4%, specificity of 72.7%, and accuracy of 76.0% in the internal testing cohort, and 0.944, 100%, 77.8%, and 86.7% in the external testing cohort. Calibration curved showed that the predicted probability by the model was comparable to the real progression of PCLs. Hosmer-Lemeshow goodness-of-fit test affirmed the model's consistency with actual PCLs progression in testing cohorts. Conclusions:The SVM model based on clinical and CT features can help doctors predict the PCLs progression within three-year follow-up, thus achieving efficient patient management and rational allocation of medical resource.

During the complete denture restoration process, accurate impression making is a crucial step for achieving good denture retention. With the increasing popularity of intraoral scanning technology in fixed restoration, the use of intraoral scanning technology in complete denture restoration for edentulous jaw has also been developed. This article systematically reviews the research progress and application of intraoral scanning of edentulous soft tissue, focusing on difficulties in intraoral scanning of edentulous jaws, scanning accuracy, clinical application effects, as well as precautions involved. The aim is to provide references for clinical application.