OBJECTIVE To identify tortoiseshell glue and antler glue in Qichong zuogui granules， and determine the contents of 12 chemical components. METHODS Identification and content determination were performed by using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. The identification was performed on Hypersil GOLD column with a mobile phase consisted of acetonitrile-0.1% formic acid solution （gradient elution）； the electrospray ion source was used to scan in the positive ion multi-reaction detection mode. The mass charge ratio （m/z） 631.3→546.4， 631.3→921.4 was the detection ion pair for tortoiseshell glue， and the m/z 765.4→554.0， 765.4→733.0 was the detection ion pair for antler glue. The determination method for 12 chemical components was as follows： Accucore C18 column， methanol-0.1% formic acid as mobile phase （gradient elution）； scanning range of positive and negative ions was m/z 100→1 000 with the electric spray ion source and single ion detection scanning mode. RESULTS Average retention times of the molecular ion peaks for characteristic peptide segments of tortoiseshell glue and antler glue were 6.28 and 6.77 min， respectively； the linear relationship of 12 chemical components was good within their respective concentration ranges， such as astragaloside Ⅳ， calycosin-7-O-β-D-glucoside， calycosin， chlorogenic acid， ferulic acid， betaine， amygdalin， rutin， hydroxysafflor yellow A， hyperoside， loganin， cyasterone （r＞0.999）； RSDs for precision， stability （24 h） and reproducibility tests were all less than 5%. The average sample recovery rates ranged from 98.04% to 101.08%. The average contents of 12 components were 1.83， 25.73， 13.76，56.71， 23.80， 49.82， 807.49， 15.01， 317.02， 60.21， 202.71 and 17.70 μg/g， respectively. CONCLUSIONS In this study， tortoiseshell glue and antler glue in Qixiong zuogui granules are identified， and the contents of 12 chemical components therein are determined. This provides a reference for the quality control of this granule.

ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula （活血消异方， HXF） in treating ovarian endometriosis （OEM） from the perspective of T follicular helper （Tfh） cells and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups， HXF group， model group， and normal group， with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling， the treatment group received HXF at 5.85 g/（kg·d） by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues， and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 （CXCR5） and interleukin-21 （IL-21） in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21， IL-21 receptor （IL-21R）， Janus kinase 1 （JAK1）， signal transducer and activator of transcription 6 （STAT6）， and B-cell lymphoma 2 （Bcl-2）. Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly， the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group， but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues， ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores， higher CXCR5 and IL-21 expression， and elevated levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2 proteins. Compared with the model group， HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.

Objective To compare the differences in alkaloids between Nelumbinis Semen and Nelumbinis Plumula and their inhibitory effects on the proliferation of HepG2 cells, and investigate the material basis for their anti-cancer activity differences. Methods Simultaneous Thermal Analysis was used to preliminarily compare the component differences between Nelumbinis Semen and Nelumbinis Plumula. Alkaloids were extracted from them by both using reflux extraction, and their contents were measured by UV and HPLC methods. The CCK-8 method was used to assess the in vitro inhibitory effects of the alkaloids on the HepG2 cells, and to verify pharmacological differences. Results Simultaneous thermal analysis revealed distinct peak shapes, positions, and sizes in the thermal analysis curves of Nelumbinis Semen and Nelumbinis Plumula at respective temperature stages. The contents of total alkaloids showed as follows: the total alkaloids in Nelumbinis Plumula > total extract of Nelumbinis Plumula > the total alkaloids in Nelumbinis Semen. The total alkaloids in Nelumbinis Plumula effectively inhibited HepG2 cell proliferation, while the total alkaloids in Nelumbinis Semen showed no impact. Conclusion Differences in the composition and content of alkaloids may be key factors underlying the biological activities differences between Nelumbinis Semen and Nelumbinis Plumula. This study provided a basis for exploring the material foundation of the differential efficacy and properties of Nelumbinis Semen and Nelumbinis Plumula, which could support their rational clinical application.

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.

Objective To investigate the temporal properties of dynamic functional connectivity of brain networks and the variability of network topology in patients with end-stage renal disease(ESRD).Methods Data of 30 ESRD patients(ESRD group)and 33 healthy subjects(control group)were retrospectively analyzed.Based on cranial resting-state functional MRI(rs-fMRI),dynamic functional connectivity(dFC)and graph theory analysis were employed,and the abnormalities in network topology and dFC in ESRD patients were assessed through comparison of groups.Pearson correlation analysis was used to observe the correlation between abnormal dFC indicators and clinical variables.Results Compared with control group,temporal scores and the mean residence time in ESRD group were significantly higher under state Ⅱ but significantly lower under state Ⅲ(both P＜0.05).The abnormal functional connectivity in ESRD patients under states Ⅱ and Ⅲ distributed mainly within and between default mode network,sensorimotor network,subcortical nuclei,execution and attention network,visual network and cerebellum networks.Network density and bilateral superior temporal gyrus nodal degrees in ESRD group were all significantly lower than those in control group(all P＜0.05).No significant correlation was found between the abnormal parameters of functional connectivity and graph theory attributes in ESRD group and clinical indicators under states Ⅱ nor Ⅲ(all P＞0.05).Conclusion ESRD patients had abnormal temporal attributes and network topology of brain dynamic networks related to cognitive impairments.

Objective:To analyze clinical efficacy, failure mode and prognostic factors of nasopharyngeal carcinoma (NPC) patients undergoing intensity modulated radiation therapy (IMRT).Methods:Clinical data of 951 locally advanced NPC patients who were newly-treated with IMRT in Hunan Cancer Hospital from January 2018 to January 2019 were retrospectively analyzed. The patients' general data, overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), local recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were analyzed. Comparison among different groups was performed by one-way ANOVA. Survival rate was calculated by Kaplan-Meier method. Survival difference was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression model.Results:The median follow-up time was 62.0 months (IQR, 58.0-65.0 months). The 5-year OS, LRFS, RRFS, LRRFS, DMFS, and PFS were 85.4%, 94.0%, 97.7%, 92.6%, 85.7% and 76.9%, respectively. According to the 8th edition staging of American Joint Committee on Cancer (AJCC), there were 10 cases (1.1%) of stage I, 76 cases (8.0%) of stage II, 445 cases (46.8%) of stage III, and 420 cases (44.2%) of stage IVA, respectively. Among them, the OS rates of stage I, II, III and IVA patients were 100%, 97.2%, 88.8% and 79.2%, respectively ( P<0.001); LRRFS rates were 100%, 90.4%, 94.7% and 90.4%, respectively( P=0.104); DMFS rates were 90.0%, 95.9%, 88.0% and 81.1%, respectively ( P<0.001); PFS rates were 90.0%, 89.1%, 80.9% and 70.1% respectively ( P<0.001). There were 183 cases of treatment failure, including 52 cases (5.5%) of local failure, 19 cases (2.0%) of regional failure, 130 cases (13.7%) of distant metastasis, 16 cases of local combined with regional failure (1.7%), 16 cases (1.7%) of local failure combined with distant metastasis, 13 cases (1.4%) of regional failure combined with distant metastasis, and 9 cases (0.9%) of local regional failure combined with distant metastasis, respectively. Multivariate regression analysis suggested that EB virus DNA copy number before treatment, T stage and N stage were the independent prognostic factors affecting OS, DMFS and PFS. Conclusions:Compared with two-dimensional radiotherapy, IMRT has improved the overall therapeutic effect for NPC, especially the local control rate. Distant metastasis is still the main failure mode. Clinical staging, prognostic risk stratification and prognostic biomarkers can be combined to deliver stratified and precise treatment, which may further improve clinical efficacy and reduce treatment-related side effects.

Objective:To analyze the value of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in the detection of myocardial injury in patients treated with anti-tumor therapy. Methods:A retrospective study was conducted on 164 patients who underwent 68Ga-FAPI-04 PET/CT to evaluate the efficacy of anti-tumor therapy in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2021 and March 2024. The patients were divided into 68Ga-FAPI-04-positive group ( n=63, 36 males, 27 females, age (66.7±9.6) years) and 68Ga-FAPI-04-negative group ( n=101, 42 males, 59 females, age (55.2±14.1) years) based on the uptake of left ventricular myocardium (LVM). Moreover, FAPI-04 uptake was analyzed based on different types and locations, and the corresponding SUV max differences were analyzed by Kruskal-Wallis rank sum test. The differences of SUV max between 68Ga-FAPI-04-positive group and 68Ga-FAPI-04-negative group were analyzed by Mann-Whitney U test. The clinical factors such as gender, age, body mass index (BMI), previous history of coronary heart disease, left ventricular ejection fraction (LVEF), smoking history, hypertension, diabetes, cancer types and immune checkpoint inhibitors (ICIs) treatment were collected, and their predictive values for LVM 68Ga-FAPI-04 uptake were investigated by the binary logistic regression analysis. Results:Fifty patients of the 68Ga-FAPI-04-positive group (79.4%, 50/63) showed focal uptake of LVM, 7 patients (11.1%, 7/63) showed multifocal myocardial uptake, and 6 patients (9.5%, 6/63) showed diffuse myocardial uptake. A total of 127 uptake lesions were found, and most of them were located in the septum (37.8%, 48/127). The SUV max of LVM in 68Ga-FAPI-04-positive group and 68Ga-FAPI-04-negative group were 4.00(3.10, 5.40) and 1.31(1.20, 1.40) respectively ( z=-10.82, P<0.001). Differences of the SUV max among focal uptake group, multifocal myocardial uptake group, and diffuse myocardial uptake group were not significantly different (4.00(3.00, 5.10) vs 7.60(3.60, 9.30) vs 3.95(3.05, 5.05); H=3.81, P=0.149). There is no statistically significant difference either in FAPI uptake among different sites of LVM ( H=1.51, P=0.825). Age, previous history of coronary heart disease, BMI, LVEF and ICIs treatment were independent predictive factors for positive 68Ga-FAPI-04 uptake in the LVM (odds ratio ( OR) values: 0.87-10.43, all P<0.05). Conclusion:68Ga-FAPI-04 PET/CT is a potential new imaging method for the visualization of myocardial injury in patients with anti-tumor therapy.

Objective To establish an artificial intelligence (AI)-assisted platform for detection of parasite eggs, and to evaluate its detection efficiency and accuracy, so as to provide technical supports for elimination of parasitic diseases. Methods A total of 1 003 slides of Enterobius vermicularis, horkworm, Trichuris trichiura, Clonorchis sinensis, Taenia, Ascaris lumbricoides, Schistosoma japonicum, Paragonimus westermani and Fasciolopsis buski eggs were collected, and converted into digital images with an automatated scanning microscope to create a dataset. Based on the Object Detection platform on the Baidu Easy DL model, an AI-assisted platform for detection of parasite eggs was created through procedures of uploading, labeling, training, evaluation and optimization. Then, 70% of the datasets were randomly selected for model training, and the precision, recall and average accuracy were calculated to evaluate the effectiveness of platform for recognition of parasite eggs. In addition, the platform was deployed on the computer and smart phone terminals for use. Results An AI-assisted platform for detection of parasite eggs was successfully created. If the platform was deployed using the public cloud application programming interface (API), the average accuracy, precision and recall of the platform were 93.42%, 92.55% and 89.32% for recognition of parasite eggs. If the platform was deployed using the offline software development kit (SDK), the average accuracy, precision and recall of the platform were 92.97%, 94.78% and 87.63% for recognition of parasite eggs. In addition, the precision of the platform was 97.00% and 96.23% for identification of Taenia and C. sinensis eggs, respectively. Conclusions The AI-assisted platform for detection of parasite eggs has been successfully created, which is high in the accuracy for recognition of parasite eggs and convenient in use. This platform may provide a powerful technical support for parasitic disease diagnosis.