Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Pancreatic cancer is a highly malignant tumor of the digestive system,with a significantly lower five-year survival rate than other malignancies.Gemcitabine(GEM)is the primary chemotherapeutic agent for pancreatic cancer,but its efficacy is often limited by chemotherapy resistance of tumor.This article elaborates on the intrinsic cellular mechanism and non-cell-autonomous mechanism of GEM resistance in pancreatic cancer and summarizes how to enhance the sensitivity of pancreatic cancer cells to GEM by inducing ferroptosis through the regulation of polyunsaturated fatty acid peroxidation,iron metabolism control,and antioxidant systems,in order to investigate the association between ferroptosis and GEM resistance mechanisms and provide new directions for the clinical treatment of pancreatic cancer.

OBJECTIVES: Managing patients with refractory head and neck cancer pain is one of the more challenging issues in clinical practice, and traditional intrathecal drug delivery also fails to provide adequate analgesia. There are currently no comprehensive and effective treatment methods. This study aims to observe the efficacy and safety of treating intractable head and neck cancer pain with morphine pump via lumbar approach to the prepontine cistern. METHODS: A total of 18 patients with intractable head and neck cancer pain treated with prepontine cistern morphine pumps were selected from the Department of Pain Management, Second Xiangya Hospital, Central South University between September 2019 and July 2023. Statistical analysis was performed on patients' preoperative and postoperative (1 week, 1 month, and 2 months after surgery), Numerical Rating Scale (NRS) scores, Self-Rating Depression Scale (SDS) scores, daily oral morphine consumption, the number of daily breakthrough pain episodes, and postoperative daily intrathecal morphine dosage. RESULTS: The NRS scores, SDS scores, daily oral morphine consumption, and the number of daily breakthrough pain episodes of patients at each time point after surgery were significantly lower than before surgery (all P<0.05). With the gradual increase in the dosage of intrathecal morphine, the daily oral morphine consumption of patients at each postoperative time point was significantly reduced compared to preoperative levels (all P<0.05). The complications related to the operation were mild, including nausea in 5 cases (31.3%), headache in 2 cases (12.5%); hypotension, urine retention, hypersomnia and constipation in 1 case (6.3% each), and no serious adverse events occurred. All improved and were discharged after symptomatic treatment. CONCLUSIONS The implantation of prepontine cistern morphine pump effectively controls intractable head and neck cancer pain, demonstrating characteristics of minimal invasiveness, mild side effects, and low medication dosage under the premise of standardized procedures.
Humans ; Morphine/administration & dosage* ; Male ; Female ; Middle Aged ; Head and Neck Neoplasms/surgery* ; Analgesics, Opioid/administration & dosage* ; Cancer Pain/drug therapy* ; Pain, Intractable/etiology* ; Aged ; Adult ; Infusion Pumps, Implantable ; Pain Management/methods*

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objective To explore the synergistic therapeutic effect of sodium butyrate and Sishen pill on mice with diarrhea with kidney-yang deficiency syndrome,and provide experimental evidence for the contemporary application of classical prescriptions.Methods The diarrhea with kidney-yang deficiency syndrome mouse model was construc-ted by gavage of adenine combined with Folium sennae.Mice were given 100％Sishen pill decoction,50 mg/kg so-dium butyrate+75％Sishen pill decoction,100 mg/kg sodium butyrate+50％Sishen pill decoction,200 mg/kg so-dium butyrate+25％Sishen pill decoction,and 300 mg/mL sodium butyrate decoction by intragastric administra-tion,respectively.General condition,food and water intake,anal temperature,body weight,fecal water content,organ index,intestinal microbiota,and enzyme activity of the mice were compared.Results After treatment,the general condition,food and water intake,anal temperature,and fecal water content of the mice gradually recovered.The body weight of mice from the natural recovery group,the 200 mg/kg sodium butyrate+25％ Sishen pill group,and the 50 mg/kg sodium butyrate+75％ Sishen pill group still showed statistical differences from the normal group(P＜0.05).The body weight of mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group(34.23±4.93)g increased,close to the body weight of mice from the normal group(35.69±4.78)g.Spleen index of the mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group recovered to normal,showing significant difference from mice from the natural recovery group(P＜0.05).There were no significant differences in thymus index of mice from different groups(P＞0.05).After treatment,the mice intestinal microbiota began to recover,with no signifi-cant differences in the number of bacteria among groups(P＞0.05).Compared with the natural recovery group,the number of Escherichia coli in mice from each treatment group reduced significantly(P＜0.01),and the mice from 100 mg/kg sodium butyrate+50％ Sishen pill group had the smallest number of Escherichia coli.The number of Bifidobacteria in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group and the 50 mg/kg sodium bu-tyrate+75％ Sishen pill group recovered to the level of the normal group(P＞0.05).The mice from 100 mg/kg so-dium butyrate+50％ Sishen pill group showed a significant effect on the recovery of Lactobacillus number(P＜0.05).The amylase,lactase,and protease activities in mice from the natural recovery group were all higher than those from the normal group(all P＜0.05),and the enzyme activities in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group were closer to those from the normal group.Compared with the natural recovery group,lactase activity of mice from the 100％ Sishen pill group reduced significantly(P＜0.01),and the xylanase activity in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group was closest to the normal group.Conclusion The synergistic effect of sodium butyrate enhances the therapeutic efficacy of Sishen pill.100 mg/kg sodium buty-rate+50％ Sishen pill group showed significant improvement in mice mental status,diarrhea symptoms,intestinal enzyme activity,and microbial stability compared with other groups using sodium butyrate or Sishen pill alone.

With the rapid rise of large language models(LLM),the natural language generation capabilities of deep learning have demonstrated significant value in the medical field.However,the"closed nature"of model parameters makes them prone to generating"hallucinations",making it difficult to provide accurate answers to the latest knowledge,and the reasoning process lacks transparency and traceability.Retrieval-augmented generation(RAG)technology addresses these issues by actively connecting external information sources such as document databases and knowledge graphs during the generation process.This significantly reduces the dependence of LLM on outdated training data and introduces verifiable evidence and real-time knowledge updates into their responses.In the medical field,RAG technology effectively addresses the high-accuracy and traceability requirements of literature retrieval and clinical decision support.It is widely applied in areas such as drug discovery,pharmacovigilance,and the diagnosis and treatment of rare diseases.By integrating emerging technologies such as reinforcement learning,multimodal processing,and compliant privacy protection,RAG technology is evolving towards a more open and highly customizable direction,providing innovative intelligent solutions for medical information retrieval and decision-making support.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the effect of bone morphogenetic protein-9(BMP9)overexpression on inflammatory response and apoptosis of alveolar epithelial cells induced by lipopolysaccharide(LPS).Methods:A549 cells were stimulated with 0.1 μg/ml LPS,expressions and changes of BMP9 protein at different time points(LPS stimulation for 0 h,6 h,12 h,24 h)were detected by Western blot.Expression of BMP9 in A549 cells was up-regulated by transfection of BMP9 plasmid,and the transfection efficiency was verified by Western blot and qPCR.After 12 h of LPS stimulation,levels of inflammatory factors TNF-α,IL-6,IL-1β in cell supernatant were detected by ELISA,expressions of anti-apoptotic protein(Bcl-2)and pro-apoptotic protein(Bax)were detected by Western blot,and apoptosis of cells was detected by TUNEL staining.Results:With the extension of LPS stimulation time,expression of BMP9 was down-regulated.Overexpression of BMP9 successfully up-regulated expression of BMP9 in A549 cells.LPS stimulation promoted secretions of TNF-α,IL-6 and IL-1β from A549 cells,increased apoptosis,promoted Bcl-2 expression while inhibited Bax expression.Overexpression of BMP9 inhibited TNF-α,IL-6 and IL-1β releasing,decreased apoptosis,inhibited Bcl-2 expression,while promoted Bax expression.Conclusion:In LPS-stimulated A549 cells,BMP9 expression is gradually decreased at a time-depen-dent manner.Overexpression of BMP9 can inhibit LPS-induced inflammatory response and apoptosis in A549 cells.

Background: Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy. Raw pieces of Rhei Radix et Rhizoma (RP) are known for their strong laxative effects, often accompanied by side effects, while steamed Rhei Radix et Rhizoma pieces (SP) possess a milder laxative effect and are widely used clinically. However, there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness, particularly from a bioavailability perspective. Objective: This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics, tissue distribution, and excretion assays. Methods: An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites. Pharmacokinetic, tissue distribution, and excretion assays were conducted in constipation rats following oral administration of RP and SP. Blood, tissue, urine, and fecal samples were collected and analyzed to compare the absorption, distribution, metabolism, and excretion profiles of anthraquinones, highlighting differences in bioavailability and safety between RP and SP. Results: Compared with the RP group, the SP group showed significantly reduced area under the plasma concentration-time curve, mean residence time, and half-life time values for rhein-8-O-β-D-glucopyranoside, rhein, emodin, aloe-emodin, and their glucuronide metabolites. The clearance values were significantly increased in the SP group. These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP. Additionally, these components were primarily distributed in the large intestine, where they exerted their laxative effects. Glucuronide metabolites were mainly excreted through urination, while prototype components were excreted in both urine and feces. Notably, the cumulative excretion of aloe-emodin, emodin, rhein, and their glucuronide metabolites was significantly higher in both urine and feces after SP administration, indicating that SP enhances the excretion of these components compared with RP. Conclusion: The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion, demonstrating that the steaming process significantly promotes the elimination of key components. This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma, offering a scientific basis for the improved safety and clinical use of SP. These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines. This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Objective: To prepare platelet membrane biomimetic liposomes loaded with vincristine sulfate (VCR) for targeted delivery to tumor. Methods: Vincristine sulfate liposomes (LIPO) were prepared using the pH-gradient method, followed by the fusion of platelet membranes and subsequent drug loading to obtain platelet membrane biomimetic liposomes (PLM-LIPO). The particle size, polydispersity index (PDI), Zeta potential, and drug encapsulation efficiency (EE%) of both liposomes were characterized. The tumor-targeting capability was evaluated through in vitro cellular experiments and in vivo biodistribution studies. Results: The optimal preparation conditions for LIPO were determined as follows: DPPC-to-cholesterol molar ratio of 1∶1, internal aqueous phase of 0.3 M pH 4.0 citrate buffer, external aqueous phase of 1 M Na HPO solution, drug-to-lipid ratio of 1∶10, drug loading temperature of 60℃, and loading time of 10 minutes. The LIPO exhibited a mean particle size of (147.3±2.24) nm, PDI of 0.078±0.014, Zeta potential of (-3.54±0.75) mV, and EE% of 91.37±0.47. For PLM-LIPO, prepared via membrane fusion followed by drug loading, the mean particle size was (185.3±3.61) nm, PDI was 0.075±0.022, Zeta potential was (-18.91±1.54) mV, and EE% was 63.36±2.45. In the CD62P validation experiment, the fluorescence intensity of PLM-LIPO was five times higher than that of LIPO. In vitro cellular uptake experiments revealed that PLM-LIPO showed 1.3-fold and 1.2-fold higher uptake rates compared to LIPO at 6 h and 12 h, respectively. In vivo experiments demonstrated that 1h after administration, the accumulation of PLM-LIPO at tumor sites was 4-fold higher than that of LIPO and 6-7 times higher than that in healthy mice. Conclusion: The platelet membrane biomimetic liposomes loaded with vincristine sulfate were successfully developed. Both cellular uptake and tissue distribution studies confirmed the PLM-LIPO enhanced tumor-targeting capability.