OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Aim To determine whether the micro kinetic chro-mogenic method can meet the requirements of Chinese Pharma-copoeia,as a supplement to the existing bacterial endotoxin test method.Methods Using micro kinetic chromogenic horseshoe crab reagent,the sample volume per well was 25 μL,the detec-tion wavelength was 405 nm,the preset OD value was 0.05,and the detection was carried out by half-well enzyme plate.In accordance with the provisions of"9101 Guiding Principles for Validation of Drug Quality Analysis Methods"in the fourth part of the 2020 edition of the People's Republic of China Pharmaco-poeia,the methodological verification of 7 items of specificity,accuracy,precision,limit of quantification,linearity,range and durability was carried out according to the specific requirements of the"quantitative"item in the"Determination of Impurities".The variety suitability study was conducted on 74 batches of samples from 48 drug varieties,and 143 batches of samples from 76 drug varieties(including 133 batches of negative samples and 10 batches of positive samples)were tested daily,and the re-sults were compared with the results of traditional color rendering method.Results The method of microdynamic color develop-ment met the requirements of the Pharmacopoeia of the People's Republic of China for quantitative methods.The results of varie-tal applicability and consistency comparison showed that the mi-crodynamic color development method had better equivalence compared with the traditional color development method.Con-clusion The micro kinetic chromogenic method can be promo-ted as a supplementary alternative to the existing bacterial endo-toxin methods.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective:To construct an estimating equation to accurately reflect the aging phenomenon of the glomerular filtration rate(GFR).Methods:Healthy subjects receiving physical examinations at the First Affiliated Hospital of Nanjing Medical University between January 2017 and April 2018 were included in the study, and the aging phenomenon of renal function indicators such as serum creatinine(Scr)was used as the reference standard to evaluate the accuracy of four Scr-based GFR equations during GFR aging, including the full age spectrum(FAS)equation, the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)equation, the Osaka equation and the Xiangya equation.Results:Of 37 636 individuals receiving physical examinations, 6 534 met the criteria specified in this study.Scr, serum urea nitrogen, serum uric acid, and serum albumin showed a significant aging phenomenon( H=191.640, 196.693, 83.271, 414.585, P<0.001 for all).The GFR estimated by the four equations all decreased with aging, but the starting point and rate of decline were significantly different.The GFR aging phenomenon estimated by the FAS equation was closer to the trend of renal function indicators. Conclusions:The FAS equation may be more applicable to healthy people to understand the aging phenomenon of GFR.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Objective:To investigate the epidemiology features, intervention effects and influencing factors of thrombosis in arteriovenous graft (AVG), and to provide reference for optimizing vascular access scheme in hemodialysis patients.Methods:It was a retrospective study. The clinical and follow-up data of patients with AVG constructed in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were analyzed. According to whether AVG thrombosis occurred during the follow-up period, they were divided into thrombosis group and non-thrombosis group, and the epidemiology status, influencing factors and patency rates of AVG thrombosis were analyzed. AVG was followed up until June 30, 2023 or abandonment or death of patient or loss of follow-up. Kaplan-Meier method was used to analyze the patency rates of AVG. Log-rank test was used to compare the differences of patency rates between groups. Logistic regression model was used to analyze the influencing factors of AVG thrombosis.Results:The study included 475 AVG from 464 patients, with age of (55.50 ± 11.85) years old, 193 males (40.6%), 185 diabetes patients (38.9%) and dialysis age of 24 (1, 68) months. One hundred and fifty-four AVG (32.4%) had a total of 307 AVG thrombotic events during the follow-up of 602 (380, 920) days, with a standardized incidence of 0.34 times per patient-year. Among them, 60 cases (19.5%, 60/307) had frequent thrombosis. Kaplan-Meier survival analysis showed that AVG secondary patency rates at 2-years and 3-years in the thrombosis group and frequent thrombosis subgroup were inferior to those in the non-thrombosis group (84.0% vs. 92.5%, P=0.017; 66.5% vs. 85.7%, P<0.001; 78.9% vs. 92.5%, P=0.030; 54.6% vs. 85.7%, P<0.001). Two hundred and sixty-nine AVG thrombotic events were analyzed to evaluate the treatment effects. Endovascular interventional surgery was used for thrombectomy in 215 cases (79.9%), and hybrid surgery (endovascular interventional surgery combined with surgical incision) was used in 54 cases (20.1%), with a technical success rate of 98.9% (266/269) and a clinical success rate of 98.1% (264/269). Kaplan-Meier survival analysis showed that there were no statistically significant differences in the primary post-intervention patency rates at 90 days and 365 days, respectively (all P>0.05), and there was statistically significant difference in the primary post-intervention patency rate at 180 days (45.1% vs. 26.5%, Z=2.563, P=0.015). Multivariate logistic regression analysis showed that graft-applied type (intering as the reference, propaten OR=1.953, 95% CI 1.139-3.350, P=0.015; acuseal OR=2.628, 95% CI 1.438-4.800, P=0.002), body mass index < 18.5 kg/m 2 (18.5-24.0 kg/m 2 as the reference, OR=0.291,95% CI 0.090-0.943, P=0.040), serum albumin < 40 g/L ( OR=1.579, 95% CI 1.019-2.445, P=0.041), serum ferritin < 200 μg/L ( OR=1.818, 95% CI 1.162-2.845, P=0.009) and mean arterial pressure < 70 mmHg ( OR=7.180, 95% CI 1.339-38.501, P=0.021) were the independent influencing factors of AVG thrombosis. Conclusions:The incidence of AVG thrombotic events is 0.34 times per patient-year, mainly concentrated in a small number of patients. Thrombosis reduces the secondary patency rate of AVG. AVG thrombosis treatment with endovascular interventional surgery or hybrid surgery has a high technical success rate and a clinical success rate. The thrombosis is related to graft-applied types, nutritional status of patients and mean arterial pressure level.

Triterpenoids widely exist in nature,displaying a variety of pharmacological activities.Determining triterpenoids in different matrices,especially in biological samples holds great significance.High-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical performance.However,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical methods.Additionally,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass spectrometry.Consequently,routine HPLC analysis suffers from poor sensitivity.Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance.Considering the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rho-damines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of triterpenoids.This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids.Moreover,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.