Objective To investigate the role of activating transcription factor 4 (ATF4) in benign prostatic hyperplasia (BPH) in order to elucidate the molecular mechanism underlying BPH progression. Methods Firstly, we analyzed the correlation between the expression of ATF4 and the volume of prostate transition zone in BPH tissues using publicly available datasets. Subsequently, we explored the potential association among ATF4, epithelial-mesenchymal transition (EMT) and BPH through single-cell RNA sequencing (scRNA-seq). Finally, we validated the findings by silencing ATF4 and treating BPH cells with ATF4 protein inhibitors, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, and Western blot. Results The expression of ATF4 in BPH tissues exhibited a significant positive correlation with the volume of prostate transition zone (r=0.64, P＜0.05). scRNA-seq analysis revealed that ATF4 was significantly upregulated in the prostate epithelial cells of BPH patients (P＜0.05), and its expression demonstrated a significant positive correlation with the Hallmark EMT singscore (r=0.14, P＜0.05). In vitro experiments further indicated that knockdown of ATF4 led to a significant reduction in the proliferative activity of BPH-1 cells (P＜0.05). Similarly, inhibition of ATF4 activity resulted in a marked decrease in the proliferative capacity and EMT of BPH-1 cells (P＜0.05). Conclusion ATF4 may exert a promoting effect on BPH by modulating the EMT signaling pathway;therefore, ATF4 may serve as a novel therapeutic target of BPH.

Objective To provide a comprehensive and multi-dimensional objective assessment of the online medi-cal service quality supplied by public hospitals in China,and providing feasible suggestions for further improving.Methods It adopted a standardized patient method and relied on the IOM model to conduct a descriptive analy-sis of the online medical service quality from the perspectives of safety and effectiveness,efficiency,patient-cen-tered care,and accessibility.Results The process quality(adherence to checklist)in public hospital was 17.65％,the diagnostic accuracy was 66.04％,and the treatment correctness was 88.68％.The average consultation fee was 50 yuan.The patients'disease experience was 4.00 points,the social situation was 0,and the agreement between the physician and the patient was 12.00 points.The average time waiting for first response was about 1.60 hours,the average time waiting for each response was about 5.14 hours,and the patient's total time was about 20.32 hours.The time for response was 3,and the total words of providers was 149.50.Conclusion Internet medical ser-vices quality in public hospital are still insufficient in three aspects:the process quality(adherence to checklist),pa-tient-centered care,and accessibility.Improving online medical service quality can be achieved by strengthening"in-process supervision"and improving physicians'comprehensive clinical ability.

Objective:To provide a scoping review of domestic and international studies on the influencing factors of frailty in stroke inpatients, and to provide guidance for interventional studies on debility in stroke inpatients in China.Methods:A systematic search of domestic and international literature databases, including China National Knowledge Infrastructure, WanFang, VIP, China Biomedical Literature Database, PubMed, Web of Science, Embase, Cochrane Library, CINAHL was conducted about the status and its influencing factors of frailty in stroke inpatients. The retrieval time limit was from database establishment to November 23, 2023. The included literature was extracted, analyzed, and summarized according to the reporting specifications of the scope review guidelines.Results:Thirty-six articles were included, all of the 36 papers reported the prevalence of frailty in patients with stroke. The top three countries with the highest prevalence were China (15.3%-86.9%), the United Kingdom (28%-78%), and Italy (31.37%). The risk factors of stroke frailty were categorized mainly into 4 themes: social demographic factors, physical health factors, disease-related factors, and psychological and social background factors.Conclusions:The confidence of frailty in stroke patients of a higher level at home and abroad, and the risk factors involved are complex and diverse. It is suggested that future studies need to conduct large-sample, multicenter longitudinal studies to clarify the causal relationship, strengthen the exploration of controversial factors of stroke debility, and carry out more targeted intervention studies, so as to reduce the incidence of frailty and improve the recovery process of patients.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

OBJECTIVE To explore the mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis(RA).METHODS The targets of main saponins in C.robustum Maxim were obtained from Swiss Target Prediction,and the RA treatment targets collected from the GeneCards and OMIM database were intercrossed to establish an interaction network based on network pharmacology.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed.RA model was established by injecting complete Freund's adjuvant into the back of rabbits for verification.The arthritis index score,knee diameter and pain threshold of rabbits were compared.Pathological examination of rabbit synovial tissue was carried out.The levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β)and IL-6 in rabbit serum and synovial fluid were detected.The phosphorylation levels of tyrosine protein Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)proteins in rabbit synovium were detected.RESULTS Network pharmacology identified 143 intersection targets between the drug and RA.After the construction of the"drug-component-target"network,the core components of the network were echinocystic acid,oleanolic acid,hederagenin,cauloside A and cauloside C,etc.Additionally,the top 10 core targets of PPI network were SRC,STAT3,MAPK1,EGFR,PIK3CA,MAPK3,GRB2,JUN,PTPN11 and JAK2.The results of KEGG pathway analysis showed that the JAK/STAT signaling pathway was mainly involved in the treatment of RA by joint injection of C.robustum Maxim.Results of validation test showed that compared with model group,joint injection of C.robustum Maxim could reduce the swelling of rabbit knee joint,relieve the hyperplasia of synovial layer,reduce the hyperplasia of lower connective tissue,and reduce the number of inflammatory cells and capillaries.The arthritis index score(excluding low-dose group of C.robustum Maxim),knee diameter,the levels of TNF-α,IL-1β and IL-6 in serum and synovial fluid,and the protein phosphorylation levels of JAK2 and STAT3 were decreased significantly(P＜0.05 of P＜0.01),while the pain threshold were reduced significantly(P＜0.01).CONCLUSIONS The core components that may alleviate the inflammatory response of RA in joint injection of C.robustum Maxim could include echinocystic acid,oleanolic acid,hederagenin,cauloside A,and cauloside C.Its mechanism may be related to the inhibition of JAK/STAT signaling pathway and the reduction of inflammatory responses.

Objective:To evaluate the safety and efficacy of secondary transport on extracorporeal membrane oxygenation (ECMO) for critically ill children.Methods:This was a retrospective cohort study. Data from 222 pediatric patients who underwent ECMO transport from May 2019 to May 2024 at 5 ECMO centers and Chinese Database of Pediatric Extracorporeal Life Support Organization were collected. The cases were divided into primary and secondary transport groups by nature of transport. The clinical data, including demographics, ECMO indications, transport distance, pre-transport lab results, prognosis and complications were analyzed. Two independent samples t-test, Wilcoxon test, and χ2 test or Fisher′s exact probability method were used to compare the differences between 2 groups and evaluate the safety and efficacy of secondary transport. Results:Among the 222 children transported with ECMO, there were 135 males and 87 females, with an age of 3.0 (0.2, 7.0) years. There were 202 cases in the primary transport group and 20 cases in the secondary transport group. All secondary transport patients had failed attempts at weaning ECMO before transfer. The patients in the secondary transport group were older, had higher rates of surgical cannulation, circulatory support, and pre-ECMO lactate levels compared to the primary transport group (7.0 (2.8, 10.0) vs. 3.0 (0.2, 6.0) years old, 55.0% (11/20) vs. 3.6% (7/202), 80.0% (16/20) vs. 41.6% (84/202), (10±4) vs. (7±6) mmol/L, Z=3.41, χ 2=66.31, 10.99, t=2.24, all P<0.05). In the secondary transport group, the vasoactive-inotropic scores of patients on circulatory support and the oxygenation index for patients requiring respiratory support were higher than those in the primary transport group (83±33 vs. 82±68, 51.0±1.8 vs. 37.4±10.2, t=2.36, 2.63, respectively; both P<0.05). There were no statistically significant differences between the 2 groups in sex, transport distance, pre-ECMO creatinine, arterial blood gas BE values, and ECMO duration (all P>0.05). No life-threatening complications occurred during the transport in either group. Two patients in the secondary transport group underwent heart transplantation, and 1 patient underwent radiofrequency ablation. The overall survival rate between the 2 groups showed no statistically significant difference (45.0% (9/20) vs. 55.4% (112/202), χ2=1.15, P>0.05). Conclusions:Secondary ECMO transport for critically ill children don't increase mortality or life-threatening complications during transport. ECMO patients who cannot receive effective treatment locally can benefit from secondary transport to an advanced ECMO center provides further treatment opportunities.

Objective To investigate the effectiveness of electro-ultrasound therapy in preventing postoperative re-adhesion in patients with moderate to severe intrauterine adhesion(IUA)who have undergone transcervical resection of adhesions(TCRA).Methods A total of 105 patients with IUA admitted to the Fifth Affiliated Hospital of Zhengzhou University from November 2022 to December 2023 were selected as the research objects.The subjects were divided into two groups based on whether they received electro-ultrasound therapy postoperatively:Control group(n=56)and electro-ultrasound group(n=49).Pre-and post-treatment conditions of endometrial thickness,uterine cavity volume,volumetric blood flow parameters and hemodynamic parameters of arteries in different parts of the uterus(uterine arteries,sub-endometrium,intra-endometrial)were compared between two groups,The pregnancy status of two groups within one year after the treatment was followed-up.Results After treatment,both groups showed significant improvement in endometrial thickness,uterine cavity volume,volumetric blood flow parameters,and hemodynamic parameters of arteries in different parts of the uterus(uterine arteries,sub-endometrium,intra-endometrial)compared to their pre-treatment values in the same group(P＜0.05),with electro-ultrasound group showing more pronounced improvement(P＜0.05).Within one year after treatment,the pregnancy rate of electro-ultrasound group was higher than that of control group(P＜0.05).Conclusion Electro-ultrasound therapy helps prevent re-adhesion following TCRA in patients with intrauterine adhesions,contributing positively to the improvement of clinical efficacy.

Objective To provide a comprehensive and multi-dimensional objective assessment of the online medi-cal service quality supplied by public hospitals in China,and providing feasible suggestions for further improving.Methods It adopted a standardized patient method and relied on the IOM model to conduct a descriptive analy-sis of the online medical service quality from the perspectives of safety and effectiveness,efficiency,patient-cen-tered care,and accessibility.Results The process quality(adherence to checklist)in public hospital was 17.65％,the diagnostic accuracy was 66.04％,and the treatment correctness was 88.68％.The average consultation fee was 50 yuan.The patients'disease experience was 4.00 points,the social situation was 0,and the agreement between the physician and the patient was 12.00 points.The average time waiting for first response was about 1.60 hours,the average time waiting for each response was about 5.14 hours,and the patient's total time was about 20.32 hours.The time for response was 3,and the total words of providers was 149.50.Conclusion Internet medical ser-vices quality in public hospital are still insufficient in three aspects:the process quality(adherence to checklist),pa-tient-centered care,and accessibility.Improving online medical service quality can be achieved by strengthening"in-process supervision"and improving physicians'comprehensive clinical ability.

Objective:To explore the current status and influencing factors of family resilience in primary caregivers of advanced cancer patients.Methods:A convenience sampling method was used to select the primary caregivers of advanced cancer patients from the Department of Gastrointestinal Oncology at Beijing Cancer Hospital, between July 2023 and March 2024. A questionnaire survey was conducted using a general information survey, the Family Hardiness Index, the General Self-Efficacy Scale, and subscales for intimacy, emotional expression, and conflict in the Family Environment Scale.Results:A total of 130 questionnaires were distributed, and 120 valid questionnaires were returned, resulting in an effective response rate of 92.31%. The family Hardiness Index score of the 120 primary caregivers was (61.03±6.44) , with scores for the responsibility dimension at (29.35±3.32) , the control dimension at (16.97±2.78) , and the challenge dimension at (14.72±2.17) . The General Self-Efficacy Scale score was (2.60±0.57) , and the Family Environment Scale scores were as follows: intimacy (8.13±1.45) , emotional expression (5.40±1.71) , and conflict 2.00 (1.00, 3.00) . Multiple linear regression analysis showed that emotional expression in the family environment ( P=0.001) , self-efficacy ( P<0.001) , and marital status ( P=0.017) were significant factors influencing family resilience in primary caregivers, explaining 27.2% of the total variance. Conclusions:The family resilience of primary caregivers of advanced cancer patients is at a moderate to high level. Caregivers with spouses, better emotional expression among family members, and higher self-efficacy tend to have higher levels of family resilience.

Objective:To investigate the value of quantitative parameters of dual-layer detector spectral CT (DLCT) in preoperative prediction of lymphovascular invasion (LVI) in invasive lung adenocarcinoma.Methods:This study employed a cross-sectional design. The data of 91 patients with primary lung adenocarcinoma confirmed by postoperative pathology who underwent DLCT enhanced scanning in the First Affiliated Hospital of Zhengzhou University from March 2022 to July 2024 were retrospectively collected. The patients were divided into LVI positive group and LVI negative group according to the postoperative pathology. Gender, age, smoking status, and lesion location were recorded,the clinical T-stage and N-stage were evaluated. Spectral base data images were generated based on the spectral reconstruction algorithm. Conventional CT features such as the size and density of the lesions were analyzed. The DLCT quantitative parameters such as 40 keV single-energy CT value (CT 40 keV), iodine density (ID), standardized iodine density (NID), and effective atomic number (Z eff) were measured. The differences of parameters between the two groups were compared using t-test, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analysis was used to identify independent factors for predicting invasive lung adenocarcinoma LVI. The predictive performance of individual parameters and their combinations for LVI in invasive lung adenocarcinoma was evaluated using receiver operating characteristic curve analysis and area under the curve (AUC) measurements. Results:There were significant differences in age, T stage, N stage, maximum diameter, focal density, and arteriovenous stage NID and Z eff between the LVI positive group and the LVI negative group ( P<0.05). Multiple logistic regression analysis showed that age ( OR=0.890, 95% CI 0.821-0.966), N stage( OR=12.721, 95% CI 2.676-60.473) and venous stage Z eff( OR=0.012,95% CI 0-0.668) were independent factors for predicting invasive lung adenocarcinoma LVI ( P<0.05). The combination of age, N stage, and venous-phase Z eff values demonstrated the highest predictive efficacy for LVI in invasive lung adenocarcinoma, with an AUC of 0.916. Conclusions:The quantitative parameters of DLCT are helpful for preoperative prediction of LVI status of invasive lung adenocarcinoma. The Z eff in the venous stage is an independent predictor, the combination of multiple parameters can further improve the diagnostic efficiency.