Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

Objective:To investigate the clinical and neonatal outcomes of nonobstructive azoospermia (NOA) patients undergoing a second microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI).Methods:A retrospective self-controll study and a cohort study were conducted in 29 NOA patients who underwent the second microTESE-ICSI treatments at the Assisted Reproduction Center of Northwest Women's and Children's Hospital between October 2013 and December 2024, with successful sperm retrieval in the first microTESE for all included patients. The sperm retrieval rate (SRR), the two-pronuclei (2PN) rate, the high-quality embryo rate, the transferable embryo rate, the blastocyst formation rate, the pregnancy and neonatal outcomes between the two microTESE-ICSI cycles were analyzed. According to whether sperm was detected during the second microTESE, the patients were divided into detected sperm group ( n=22) and without detected sperm group ( n=7). The surgical interval, preoperative hormone levels, testicular volume, and patient pathological type were compared between the two groups. Patients who had achieved at least one biochemical pregnancy in the first cycle were classified as the pregnancy group, while those who had not achieved a biochemical pregnancy were classified as the non-pregnancy group, and the pregnancy outcomes of patients during the second microTESE-ICSI treatment were compared between the two groups. Previous surgical recordings were also analyzed. Results:The SRR of the second microTESE was 75.9% (22/29). There were no statistically significant differencs in surgical interval, preoperative hormones level, testicular volume, and patient pathological type between detected sperm group and without detected group during the second examination (all P>0.05). SRR showed no difference between idiopathic and non-idiopathic NOA ( P>0.05). 2PN rate, high-quality embryo rate, transferable embryo rate, blastocyst formation rate did not differ statistically between the two cycles (all P>0.05). Among patients completing follow-up in the second microTESE-ICSI cycle, cumulative pregnancy and live birth rates after all embryos transfer were 52.4% (11/21) and 42.9% (9/21), respectively. Further analysis revealed that patients in pregnancy group [75.0% (6/8)] had significantly higher cumulative live birth rate than that in non-pregnancy group [23.1% (3/13), P=0.032] in the second cycle. No birth defects were observed in neonates. Surgical video review suggested that excessive microdissection and low-magnification electrocautery hemostasis might increase intratesticular scarring. Conclusion:For NOA patients with failed initial microTESE-ICSI, the second treatment can effectively retrieve sperm and achieve favorable pregnancy and neonatal outcomes. Patients with prior biochemical pregnancy may benefit from higher live birth rate in subsequent cycles.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.

Objective To identify risk factors for colorectal adenomatous polyps using logistic regression analysis,construct a prediction model based on these identified factors,and subsequently evaluate the performance of the model.Methods Encompassed 1,023 patients who underwent large intestine polyp resection at the First Hospital of Handan between January 2017 and January 2022.Among these patients,676 had adenomatous polyps(adenomatous polyp group)and 347 had non-adenomatous polyps(non-adenomatous polyp group).We collected data on basic information,medical history,colonoscopy results,and polyp pathology.By comparing the two groups,we identified significant differences in various indicators,which were selected as candidate factors for model construction.Patients were randomly divided into a training set and a validation set at an 8∶2 ratio.Using the training set data,we constructed a risk prediction model and developed a nomogram using R Studio software to visually present the model.Finally,we internally validated the model using the validation set.The model's discrimination ability was evaluated using the ROC curve,its accuracy was assessed via the calibration curve,and its clinical utility was evaluated through decision curve analysis(DCA).Results Significant differences were observed between the two groups in terms of age,drinking habits,family history of colorectal cancer,hyperlipid-emia,history of cholecystectomy,HP infection,and history of appendectomy(P<0.05).These variables were included in the model construction.A total of 818 participants were randomly assigned to the training set,while 205 were allocated to the validation set.Multivariate logistic regression analysis on the training set confirmed that age(OR=1.021,95%CI:1.006～1.036,P=0.006),alcohol consumption(OR=3.440,95%CI:2.251～5.257,P<0.001),first-degree relatives with colorectal cancer(OR=3.775,95%CI:1.881～7.577,P<0.001),hyperlipidemia(OR=3.428,95%CI:2.443～4.808,P<0.001),history of cholecystectomy(OR=3.916,95%CI:1.756～8.735,P<0.001),Helicobacter pylori(HP)infection(OR=3.292,95%CI:2.309～4.693,P<0.001),and history of appendectomy(OR=3.819,95%CI:2.002～7.286,P<0.001)were independent risk factors for adenomatous polyps.Consequently,a prediction model for large intestine adenomatous polyps was developed using the formula P=1/(1+e-Y),where Y=0.020×age+1.328×first-degree relatives with colorectal cancer+1.235×alcohol consumption+1.232×hyperlipidemia+1.365×cholecystectomy+1.192×HP infection+1.340×appendectomy-1.995.The model demonstrated good performance with AUC values of 0.763(95%CI:0.729～0.797)for the training set and 0.769(95%CI:0.644～0.787)for the validation set.The calibration curve indicated a good fit,and decision curve analysis showed that the model could achieve positive net benefit across a wide range of threshold probabilities,confirming its clinical utility.Conclusions Age,alcohol consumption,a family history of colorectal cancer in first-degree relatives,hyperlipidemia,cholecystectomy,HP infection,and appendectomy were identified as independent risk factors for adenomatous polyps.A prediction model incorporating these risk factors holds significant practical value for predicting the occurrence of colorectal adenomatous polyps.

Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

Objective To construct a surgical pharmaceutical risk management index system and then to enhance surgi-cal pharmaceutical service quality.Methods Literature research and consulting pharmaceutical experts were used to collect relevant data and construct initial scale items.The Delphi expert consultation method was used to revise and improve indicators with 20 experts,after 2 rounds of inquiry improvement.The analytic hierarchy process(AHP)was used to calculate the weight of each indicator,finally forming the surgical pharmaceutical risk management index system.Results The final construction of the scale entries includes four dimensions,14 second-grade indexes,and 71 third-grade indexes.The questionnaire response rates were 100.00％,while the authority coefficient of experts was 0.832.In the consultation,the harmony coefficients of the first,second,and third indicators were 0.743,0.491,and 0.277,respectively.The AHP was used to determine the weights of indicators,and the re-sult passed the consistency test.The professional factors and pharmacist factors of the first indicators are large in weight.Con-clusion The constructed surgical pharmaceutical risk management index system is scientific and practical,which can provide a reference for the clinical work of surgeons and maximize the risk of avoidance.

Objective:To explore biomarkers for the efficacy of lymphocyte immunotherapy (LIT) treating women with unexplained recurrent spontaneous abortion (URSA).Methods:Serum samples from 24 URSA potients who received LIT were collected at Peking University Third Hospital from December 2014 to June 2015. Semiquantitative sandwich-based antibody arrays containing 40 cytokines were used to screen target immune cytokines in the peripheral blood of URSA patients before and after LIT. Multifactor quantitative microsphere flow cytometry detection validated the levels of target cytokines. Based on the final pregnancy outcome after LIT, 24 URSA patients were divided into the full-term delivery group (15 cases) and the abortion group (9 cases). Furthermore, linear regression analysis were applied to evaluate the relationship between target cytokines and pregnancy outcomes.Results:Semiquantitative sandwich-based antibody arrays suggested that, among all 24 URSA patients included in this study, the intensities of the fluorescence signal were significantly lower post-LIT versus pre-LIT for the following cytokines: interleukin-15 (IL-15), monokine induced by γ-interferon (MIG), C-C motif chemokine ligand (CCL) 1 (all P<0.05). In the full-term delivery group, the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines: IL-15, CCL1, macrophage inflammatory protein (MIP) 1α (all P<0.05). In the abortion group, the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines: MIG, MIP-1δ (all P<0.05). Linear regression analysis showed that the intensity of the fluorescence signal of CCL11 was increased and the intensity of the fluorescence signal of soluble tumor necrosis factor receptor 2 (sTNFR2) was decreased in the full-term delivery group after LIT, the differences were statistically significant ( P=0.012, 0.029). Validation results of multifactor quantitative microsphere flow cytometry detection showed that the level of CCL11 was significantly increased ( P=0.001) and the level of sTNFR2 was significantly decreased ( P=0.001) in the full-term delivery group after LIT. Conclusion:CCL11 and sTNFR2 maybe serve as potential biomarkers that could predict pregnancy outcomes after LIT in women with URSA.

The wide application of assisted reproductive technology (ART) has brought the hope of fertility to infertile couples worldwide. However, with the gradual popularization of ART, the long-term health status of ART children has attracted extensive attention from society. Adolescence is a critical developmental period for individuals to transition from childhood to adulthood, with significant physical and psychological changes, so the health status of ART offspring during this period has a profound impact on their overall future health. This article reviews the existing studies, focusing on the effects of ART on multiple aspects of adolescent health, especially growth and development, cardiovascular health, endocrine function, fertility, cancer risk, atopic diseases, mental health, epigenetic changes and other aspects. The possible mechanisms leading to these health problems, including genetic factors, environmental exposures, and the long-term effects of early life interventions, were explored. Future research should continue to explore the long-term effects of ART on the health of offspring and further clarify the mechanisms of these effects, so as to provide a scientific basis for the development of effective prevention and intervention measures.

Objective:To investigate the clinical and neonatal outcomes of nonobstructive azoospermia (NOA) patients undergoing a second microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI).Methods:A retrospective self-controll study and a cohort study were conducted in 29 NOA patients who underwent the second microTESE-ICSI treatments at the Assisted Reproduction Center of Northwest Women's and Children's Hospital between October 2013 and December 2024, with successful sperm retrieval in the first microTESE for all included patients. The sperm retrieval rate (SRR), the two-pronuclei (2PN) rate, the high-quality embryo rate, the transferable embryo rate, the blastocyst formation rate, the pregnancy and neonatal outcomes between the two microTESE-ICSI cycles were analyzed. According to whether sperm was detected during the second microTESE, the patients were divided into detected sperm group ( n=22) and without detected sperm group ( n=7). The surgical interval, preoperative hormone levels, testicular volume, and patient pathological type were compared between the two groups. Patients who had achieved at least one biochemical pregnancy in the first cycle were classified as the pregnancy group, while those who had not achieved a biochemical pregnancy were classified as the non-pregnancy group, and the pregnancy outcomes of patients during the second microTESE-ICSI treatment were compared between the two groups. Previous surgical recordings were also analyzed. Results:The SRR of the second microTESE was 75.9% (22/29). There were no statistically significant differencs in surgical interval, preoperative hormones level, testicular volume, and patient pathological type between detected sperm group and without detected group during the second examination (all P>0.05). SRR showed no difference between idiopathic and non-idiopathic NOA ( P>0.05). 2PN rate, high-quality embryo rate, transferable embryo rate, blastocyst formation rate did not differ statistically between the two cycles (all P>0.05). Among patients completing follow-up in the second microTESE-ICSI cycle, cumulative pregnancy and live birth rates after all embryos transfer were 52.4% (11/21) and 42.9% (9/21), respectively. Further analysis revealed that patients in pregnancy group [75.0% (6/8)] had significantly higher cumulative live birth rate than that in non-pregnancy group [23.1% (3/13), P=0.032] in the second cycle. No birth defects were observed in neonates. Surgical video review suggested that excessive microdissection and low-magnification electrocautery hemostasis might increase intratesticular scarring. Conclusion:For NOA patients with failed initial microTESE-ICSI, the second treatment can effectively retrieve sperm and achieve favorable pregnancy and neonatal outcomes. Patients with prior biochemical pregnancy may benefit from higher live birth rate in subsequent cycles.

Objective To evaluate the value of biparametric MRI(bpMRI)radiomics for predicting postoperation Gleason score(GS)upgrade of prostate cancer(PCa).Methods Totally 344 PCa patients who underwent radical prostatectomy(RP)were retrospectively enrolled and divided into training set(n=241)and test set(n=103)at a ratio of 7∶3.T2WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)map radiomics signatures were constructed based on preoperative bpMRI,respectively,then logistic regression(LR)algorithm was used to establish bpMRI radiomics model.Univariate and multivariate logistic regression analyses were performed to screen independent risk factors for postoperation GS upgrade of PCa,and a clinical model was constructed.Then a clinical-radiomics combined model was established based on clinical model and bpMRI radiomics model.Receiver operating characteristic curves were drawn,the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting postoperation GS upgrade of PCa.Results Elevated preoperative prostate imaging reporting and data system(PI-RADS)score and reduced biopsy Gleason grade group(GG)were both independent risk factors of postoperation GS upgrade of PCa(both P＜0.05).The AUC of bpMRI radiomics model and clinical-radiomics combined model for predicting postoperation GS upgrade of PCa were higher than that of single-sequence radiomics signatures and clinical model(all P＜0.05),while no significant difference was found between the former two(P＞0.05).The clinical-radiomics combined model demonstrated good efficacy for predicting postoperation GS upgrade of PCa with different biopsy GG before operation,with AUC ranging from 0.835 to 0.949 in training set and 0.803 to 0.948 in test set.Conclusion bpMRI radiomics model could effectively predict postoperation GS upgrade of PCa.