OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

Objective To explore the related risk factors of osteosarcopenia (OS) in elderly patients with type 2 diabetes mellitus (T2DM) and to evaluate their predictive value. Methods We selected 409 elderly patients with T2DM from our hospital between June 2021 and December 2024 as the study subjects, and divided them into an OS occurrence group and a non-occurrence group based on whether they were diagnosed with OS. Results Among the 409 elderly patients with T2DM included, 93 were diagnosed with OS, yielding a prevalence rate of 22.73%. Spearman correlation analysis revealed a significant association between lumbar spine BMD and T-scores with age, history of previous fractures, fasting plasma glucose (FPG), procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and 25-hydroxyvitamin D (25(OH)D). Gender (OR=0.193), Body Mass Index (BMI) (OR=0.254), history of previous fractures (OR=8.883), FPG (OR=0.543), Total Cholesterol (TC) (OR=3.684), High-Density Lipoprotein Cholesterol (HDL-C) (OR=86.024), PINP (OR=0.818), and OC (OR=0.526) are identified as influential factors for the occurrence of OS in elderly patients with T2DM. The combined prediction of these variables yields a sensitivity of 96.5%, a specificity of 97.8%, and an area under the curve (AUC) of 0.992 for the occurrence of OS in elderly patients with T2DM, indicating an excellent predictive performance. Conclusion The following factors—gender, BMI, history of previous fractures, FPG, TC, HDL-C, PINP, and OC—are influential in the occurrence of OS among elderly patients with T2DM. Formulating intervention measures based on these influencing factors can provide assistance in preventing and treating the occurrence of OS.

Purpose: In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. Methods: Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. Results: Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. Conclusion Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.

Objective To assess the effects of “dual low” scanning technology in conjunction with an individualized injection protocol in enhancing the quality of abdominal contrast-enhanced CT images. Methods A total of 200 patients who underwent abdominal contrast-enhanced CT examinations at the Hainan Western Central Hospital between January 2022 and January 2024 were selected for the study. Using a random number table, participants were randomly assigned to either a control group (n = 100, sub-hypertonic contrast agent + conventional tube voltage + individualized injection protocol) or an observation group (n = 100, isotonic contrast agent + tube voltage of 100 kV + individualized injection protocol). The study compared the impact of these two methodologies on the quality of abdominal contrast-enhanced CT images. Results During the arterial phase, the CT value of the abdominal aorta was significantly higher in the observation group than that in the control group (P < 0.05), suggesting that isotonic contrast agent and low tube voltage more effectively enhanced vascular signal. During the portal vein phase, the CT value was higher and the liver parenchymal noise was lower in the observation group those in the control group (P < 0.05), further validating the advantages of the “dual low” approach during the portal venous phase. The radiation dose was significantly lower in the observation group than that in the control group (P < 0.05), indicating that the “dual low” protocol effectively reduced radiation dose while enhancing patient safety. During the arterial phase, both the abdominal aorta noise and liver parenchymal noise were lower in the observation group than those in the control group (P < 0.05), demonstrating that the “dual low” strategy effectively reduced image noise and enhanced image clarity. The image quality scores were significantly higher in the observation group than in the control group (P < 0.05), indicating that high image quality could be achieved even at reduced radiation doses and contrast agent concentrations. Conclusion The “dual low” scanning technology, combined with an individualized injection protocol, not only effectively enhances the contrast of arteries and veins, reduces image noise, and improves the overall image quality, but also decreases radiation dose and enhances patient safety. Therefore, this technology is worth being widely promoted.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

The epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation is a rare subtype of mutations in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC carrying the EGFR ex20ins mutation tend to have poor responses to traditional EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and immunotherapy, leading to a poor clinical prognosis. Significant progress has been made in the development of new drugs targeting the EGFR ex20ins mutation. The research on new drugs targeting EGFR ex20ins mutations has made significant progress. The main ones include new EGFR-TKIs (such as sunvozertinib, mobocertinib, and furmetinib, etc.), bispecific antibodies (such as amivantamab, JMT101, and GB263T, etc.), and emerging drugs such as AUY922. These agents have demonstrated promising efficacy in clinical trials, improving the objective response rate and progression-free survival of patients, and are expected to improve overall survival. An in-depth analysis of the mechanism of action and clinical trial progress of these novel targeted drugs for EGFR ex20ins-mutated NSCLC can offer new therapeutic strategies for patients with EGFR ex20ins-mutated NSCLC.

Objective:To establish the UPLC fingerprint evaluation system of Viticis Fructus; To comprehensively evaluate the quality of Viticis Fructus and its processed products combining with multivariate statistical methods and compositional variance analysis.Methods:19 batches of Viticis Fructus from different regions were collected and processed by frying process into decoction pieces. The separation was operated on Waters CORTECS T3 C18 chromatographic column (100 mm × 2.1 mm, 1.6 μm). Acetonitrile and 0.1% phosphoric acid water were used as mobile phases for gradient elution, to establish the UPLC fingerprints of Viticis Fructus. The UPLC fingerprints of Viticis Fructus were analyzed using similarity evaluation, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA). The contents of seven active components in the samples of Viticis Fructus and fried Viticis Fructus were determined.Results:A total of 26 common peaks were identified in the fingerprints of 38 batches of samples, and 7 components were identified. Similarity evaluation results demonstrated that the chemical components of Viticis Fructus from Jingdezhen City, Jiangxi Province, were significantly different from those of other regions. The results of PCA and PLS-DA analysis showed that the chemical components of Viticis Fructus and fried Viticis Fructus could be clearly distinguished, and the processing process had an impact on the components. The results of content determination showed that the contents of some components increased or decreased after frying. The analysis results of grey correlation method and TOPSIS method show that the medicinal materials in Jiujiang City, Jiangxi Province have a high score ranking and stable quality.Conclusion:This study successfully establishes the fingerprints of Viticis Fructus and its processed products, grey correlation method and TOPSIS method analysis revealed the quality differences of samples from different origins, which providing a scientific basis for the quality control and evaluation of Viticis Fructus and its processed products.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Ulcerative colitis(UC)is an idiopathic,relapsing,and etiologically complicated chronic inflammatory bowel disease.Despite substantial progress in the management of UC,the outcomes of mucosal barrier repair are unsatisfactory.In this study,phillygenin(PHI)treatment alleviated the symptoms of chronic colitis in mice,including body weight loss,severe disease activity index scores,colon shortening,splenomegaly,oxidative stress,and inflammatory response.In particular,PHI treatment ameliorated the tight junction proteins(TJs)reduction,fibrosis,apoptosis,and intestinal stem cell activity,indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis.In the NCM460 cells damage model,dextran sulfate sodium triggered the sequential induction of TJs reduction,fibrosis,and apoptosis.Takeda G protein-coupled receptor-5(TGR5)dysfunction mediated NCM460 cell injury.Moreover,PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function,depending on TGR5 activation.PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids.Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5,indicating that PHI is an agonist of TGR5.The process of PERK-eIF2α pathway-mediated endo-plasmic reticulum Ca2+release was involved in NCM460 cell injury as well,which was associated with TGR5 dysfunction.When NCM460 cells were pretreated with PHI,the PERK-eIF2α pathway and elevated Ca2+levels were blocked.In conclusion,our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca2+pathway through TGR5 activation to against DSS-induced TJs reduction,fibrosis,and apoptosis.

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.