ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

Objective:To investigate the current awareness of large language models (LLM) among Chinese clinical physicians and analyze the application needs of cardiovascular specialists.Methods:This is a cross-sectional study utilized convenience sampling. In December 2023, a self-designed questionnaire was distributed to 7 980 clinical physicians, including 930 cardiologists. The survey collected demographic information, including work city (categorized as first-tier, new first-tier, second-tier, third-tier, and fourth-tier and below), hospital level, professional title, and department. And the awareness of LLM, and their application demands in clinical decision-making support, information filtering, and scientific research work were also collected. Differences in awareness and application requirements across geographic regions, hospital tiers, professional ranks, and medical departments were analyzed. Besides, specific demands of cardiovascular specialists were further examined.Results:Among the 7 980 clinical physicians, the awareness rate of LLM was 76.3% (6 088/7 980), and the utilization rate was 11.8% (942/7 980). For the 930 cardiologists, the awareness rate was 78.5% (730/930) and the utilization rate was 11.4% (106/930). Significant differences in awareness and utilization rates were observed across city tiers, hospital grades, and departments (all P<0.05). No significant difference was found among professional titles ( P=0.053). Among the 6 088 physicians aware of LLM, demand rates for clinical information filtering, clinical decision support, and research assistance were 87.3% (5 312/6 088), 78.4% (4 774/6 088), and 75.8% (4 616/6 088), respectively. For the 730 cardiologists aware of LLM, these rates were 91.0% (664/730), 79.2% (578/730), and 75.9% (554/730), respectively. Significant differences in demands for clinical information filtering and research assistance were observed across city tiers, hospital grades, professional titles, and departments (all P<0.05), while no significant difference was noted for decision support demands across hospital grades ( P=0.085). In clinical information screening and acquisition, cardiologists from different city tiers exhibited statistically significant differences in the demand for literature interpretation. Similarly, variations in the demand for conference summaries, expert biographies, healthcare policies, and social news were noted among cardiologists with different professional titles, while disparities in patient education and science popularization needs were identified across city tiers and hospital grades (all P<0.05). In clinical decision-making support, cardiologists from diverse city tiers and professional titles demonstrated distinct differences in guideline and consensus inquiries, and those from various city tiers showed varied demands for pharmaceutical and medical device-related content (all P<0.05). For research support, cardiologists across city tiers and professional titles exhibited statistically significant differences in trial protocol design requirements, while those from varying city tiers differed in literature search/analysis and research application procedures. Additionally, physicians from different hospital grades displayed divergent needs for data collection (all P<0.05). Conclusions:The adoption of LLM is significantly influenced by regional disparities, institutional resources, and professional backgrounds. Implementing targeted interventions, such as enhancing technical training, optimizing LLM functionalities, and improving accessibility across diverse healthcare settings, could encourage widespread integration of LLM into clinical practice. Such measures could ultimately enhance the quality and efficiency of medical services in China and foster innovations in healthcare delivery.

Objective:To analyze the current status and factors influencing clinician participation in remote patient management in China.Methods:In December 2023, a structured electronic questionnaire was administered to 7 980 clinicians, including 930 cardiologists. The survey assessed clinicians′ participation in online doctor-patient interactions; differences in hospital support across city tiers, hospital grades, professional titles, and departments; and factors influencing the willingness of clinicians to invest time in remote patient management.Results:Among the 7 980 surveyed clinicians, online consultations had the highest participation rate (72.2%). Among cardiologists, participation rates for online consultations, health education, and post-consultation management were 73.3%, 66.9%, and 38.5%, respectively, which were relatively higher than those of other specialties. Hospital-based support for physicians in remote patient management showed significant variations across specialties and regions. Among cardiologists, 68.4% received "encouraging" policies, with the majority falling under "encouragement without incentive policies" (42.6%). In tier 3 cities, the proportion of physicians receiving "encouragement without incentive policies" was the highest (47.9%), while the proportion in the "cautious, requiring reporting" category was the lowest (3.9%). During remote patient management, the proportions of clinicians receiving support from professional teams were highest among those in tier 3 cities (29.6%) and cardiologists (30.5%). A significant interaction effect was observed between hospital policy and specialty (cardiologists vs. all clinicians) regarding physicians′ willingness to invest time in remote patient management ( F=5.95, P<0.001). Among cardiologists, those working in institutions with "encouraging, with incentives" policies reported a significantly longer median weekly investment time (10.0 h) compared to those under "neutral, unrestricted" policies (7.0 h, P<0.001). Cardiologists with team support reported a significant increase in the time they were willing to invest (10 h/week) than those without team support (7.0 h/week, P<0.001), although no significant interaction effect was found when compared with all clinicians ( P=0.186). Cardiologists with a high online income (>5 000 Yuan/month) reported a significantly longer weekly investment time in remote management (25.0 h) compared to those with lower income (<200 yuan/month; 8.0 h, P<0.001). However, whether the income met their personal expectations had no significant effect on their time commitment ( P=0.638). Conclusions:Clinicians from tertiary hospitals and tier 3 cities demonstrated a higher level of engagement in remote patient management. Strengthening hospital policy support, enhancing team-based collaborations, and increasing online income levels may help promote the broader adoption of telemedicine.

A 66-year-old female kidney transplant recipient presented to Shanghai Jiao Tong University Affiliated Renji Hospital on May 24th, 2024 due to recurring intermittent diarrhea for over 16 years. The parasites were found through examination of small intestinal fluid. Small intestinal fluid mNGS combined with blood mNGS confirmed Cyclospora cayetanensis infection. The cause of the diarrhea was clarified. Oral compound sulfamethoxazole was used as treatment, and the patient's diarrhea symptoms improved, and no Cyclospora cayetanensis was found in the small intestinal fluid smear three consecutive times. Parasitic infection factors should be excluded in patients with low immune function and chronic diarrhea. Non-invasive small intestinal fluid smear combined with mNGS detection provides a new method to clarify the cause of chronic diarrhea.

Objective To investigate the effect of closed-chain exercise training on hemiplegic shoulder pain and shoulder joint sta-bility in stroke patients,and to explore the relationship between hemiplegic shoulder pain and shoulder joint sta-bility.Methods A total of 52 stroke patients with hemiplegic shoulder pain in Jiangsu Province Hospital from October,2020 to January,2023 were selected,and were randomly divided into control group(n=26)and experimental group(n=26).Both groups received conventional rehabilitation therapy,while the experimental group additionally under-went closed-chain exercise training for shoulder joint.Pain severity and motor function were assessed using Visu-al Analog Scale(VAS)and Fugl-Meyer Assessment-Upper Extremities(FMA-UE)before and after intervention.Musculoskeletal ultrasound was used to measure acromion-greater tuberosity distance(AGT),acromion-lesser tu-berosity distance(ALT),acromiohumeral distance(AHD)and supraspinatus thickness(SST)to evaluate shoulder joint stability.Correlation analysis was conducted on the improvements in shoulder pain and shoulder joint stabil-ity in the experimental group.Results Two cases in the control group and two in the experimental group dropped down.Both groups showed signifi-cant improvements in VAS and FMA-UE scores after intervention(|t|>5.214,P<0.001),and the scores im-proved more in the experimental group than in the control group(|t|>2.087,P<0.05).The experimental group also showed significant improvements in AGT,ALT,AHD and SST(|t|>4.187,P<0.001),with AGT,ALT and AHD being superior to those in the control group(|t|>2.155,P<0.05).The difference of VAS score in the exper-imental group was correlated with the difference of FMA-UE,AGT and ALT after intervention(r>0.434,P<0.05).Conclusion Closed-chain shoulder exercise training can significantly improve shoulder joint stability while alleviating shoulder pain,and effectively enhancing upper limb function in stroke patients with hemiplegic shoulder pain.Hemiplegic shoulder pain is correlated with shoulder joint stability.

Objective To investigate the effect of closed-chain exercise training on hemiplegic shoulder pain and shoulder joint sta-bility in stroke patients,and to explore the relationship between hemiplegic shoulder pain and shoulder joint sta-bility.Methods A total of 52 stroke patients with hemiplegic shoulder pain in Jiangsu Province Hospital from October,2020 to January,2023 were selected,and were randomly divided into control group(n=26)and experimental group(n=26).Both groups received conventional rehabilitation therapy,while the experimental group additionally under-went closed-chain exercise training for shoulder joint.Pain severity and motor function were assessed using Visu-al Analog Scale(VAS)and Fugl-Meyer Assessment-Upper Extremities(FMA-UE)before and after intervention.Musculoskeletal ultrasound was used to measure acromion-greater tuberosity distance(AGT),acromion-lesser tu-berosity distance(ALT),acromiohumeral distance(AHD)and supraspinatus thickness(SST)to evaluate shoulder joint stability.Correlation analysis was conducted on the improvements in shoulder pain and shoulder joint stabil-ity in the experimental group.Results Two cases in the control group and two in the experimental group dropped down.Both groups showed signifi-cant improvements in VAS and FMA-UE scores after intervention(|t|>5.214,P<0.001),and the scores im-proved more in the experimental group than in the control group(|t|>2.087,P<0.05).The experimental group also showed significant improvements in AGT,ALT,AHD and SST(|t|>4.187,P<0.001),with AGT,ALT and AHD being superior to those in the control group(|t|>2.155,P<0.05).The difference of VAS score in the exper-imental group was correlated with the difference of FMA-UE,AGT and ALT after intervention(r>0.434,P<0.05).Conclusion Closed-chain shoulder exercise training can significantly improve shoulder joint stability while alleviating shoulder pain,and effectively enhancing upper limb function in stroke patients with hemiplegic shoulder pain.Hemiplegic shoulder pain is correlated with shoulder joint stability.

Objective:To analyze the current status and factors influencing clinician participation in remote patient management in China.Methods:In December 2023, a structured electronic questionnaire was administered to 7 980 clinicians, including 930 cardiologists. The survey assessed clinicians′ participation in online doctor-patient interactions; differences in hospital support across city tiers, hospital grades, professional titles, and departments; and factors influencing the willingness of clinicians to invest time in remote patient management.Results:Among the 7 980 surveyed clinicians, online consultations had the highest participation rate (72.2%). Among cardiologists, participation rates for online consultations, health education, and post-consultation management were 73.3%, 66.9%, and 38.5%, respectively, which were relatively higher than those of other specialties. Hospital-based support for physicians in remote patient management showed significant variations across specialties and regions. Among cardiologists, 68.4% received "encouraging" policies, with the majority falling under "encouragement without incentive policies" (42.6%). In tier 3 cities, the proportion of physicians receiving "encouragement without incentive policies" was the highest (47.9%), while the proportion in the "cautious, requiring reporting" category was the lowest (3.9%). During remote patient management, the proportions of clinicians receiving support from professional teams were highest among those in tier 3 cities (29.6%) and cardiologists (30.5%). A significant interaction effect was observed between hospital policy and specialty (cardiologists vs. all clinicians) regarding physicians′ willingness to invest time in remote patient management ( F=5.95, P<0.001). Among cardiologists, those working in institutions with "encouraging, with incentives" policies reported a significantly longer median weekly investment time (10.0 h) compared to those under "neutral, unrestricted" policies (7.0 h, P<0.001). Cardiologists with team support reported a significant increase in the time they were willing to invest (10 h/week) than those without team support (7.0 h/week, P<0.001), although no significant interaction effect was found when compared with all clinicians ( P=0.186). Cardiologists with a high online income (>5 000 Yuan/month) reported a significantly longer weekly investment time in remote management (25.0 h) compared to those with lower income (<200 yuan/month; 8.0 h, P<0.001). However, whether the income met their personal expectations had no significant effect on their time commitment ( P=0.638). Conclusions:Clinicians from tertiary hospitals and tier 3 cities demonstrated a higher level of engagement in remote patient management. Strengthening hospital policy support, enhancing team-based collaborations, and increasing online income levels may help promote the broader adoption of telemedicine.

A 66-year-old female kidney transplant recipient presented to Shanghai Jiao Tong University Affiliated Renji Hospital on May 24th, 2024 due to recurring intermittent diarrhea for over 16 years. The parasites were found through examination of small intestinal fluid. Small intestinal fluid mNGS combined with blood mNGS confirmed Cyclospora cayetanensis infection. The cause of the diarrhea was clarified. Oral compound sulfamethoxazole was used as treatment, and the patient's diarrhea symptoms improved, and no Cyclospora cayetanensis was found in the small intestinal fluid smear three consecutive times. Parasitic infection factors should be excluded in patients with low immune function and chronic diarrhea. Non-invasive small intestinal fluid smear combined with mNGS detection provides a new method to clarify the cause of chronic diarrhea.

Objective:To investigate the current awareness of large language models (LLM) among Chinese clinical physicians and analyze the application needs of cardiovascular specialists.Methods:This is a cross-sectional study utilized convenience sampling. In December 2023, a self-designed questionnaire was distributed to 7 980 clinical physicians, including 930 cardiologists. The survey collected demographic information, including work city (categorized as first-tier, new first-tier, second-tier, third-tier, and fourth-tier and below), hospital level, professional title, and department. And the awareness of LLM, and their application demands in clinical decision-making support, information filtering, and scientific research work were also collected. Differences in awareness and application requirements across geographic regions, hospital tiers, professional ranks, and medical departments were analyzed. Besides, specific demands of cardiovascular specialists were further examined.Results:Among the 7 980 clinical physicians, the awareness rate of LLM was 76.3% (6 088/7 980), and the utilization rate was 11.8% (942/7 980). For the 930 cardiologists, the awareness rate was 78.5% (730/930) and the utilization rate was 11.4% (106/930). Significant differences in awareness and utilization rates were observed across city tiers, hospital grades, and departments (all P<0.05). No significant difference was found among professional titles ( P=0.053). Among the 6 088 physicians aware of LLM, demand rates for clinical information filtering, clinical decision support, and research assistance were 87.3% (5 312/6 088), 78.4% (4 774/6 088), and 75.8% (4 616/6 088), respectively. For the 730 cardiologists aware of LLM, these rates were 91.0% (664/730), 79.2% (578/730), and 75.9% (554/730), respectively. Significant differences in demands for clinical information filtering and research assistance were observed across city tiers, hospital grades, professional titles, and departments (all P<0.05), while no significant difference was noted for decision support demands across hospital grades ( P=0.085). In clinical information screening and acquisition, cardiologists from different city tiers exhibited statistically significant differences in the demand for literature interpretation. Similarly, variations in the demand for conference summaries, expert biographies, healthcare policies, and social news were noted among cardiologists with different professional titles, while disparities in patient education and science popularization needs were identified across city tiers and hospital grades (all P<0.05). In clinical decision-making support, cardiologists from diverse city tiers and professional titles demonstrated distinct differences in guideline and consensus inquiries, and those from various city tiers showed varied demands for pharmaceutical and medical device-related content (all P<0.05). For research support, cardiologists across city tiers and professional titles exhibited statistically significant differences in trial protocol design requirements, while those from varying city tiers differed in literature search/analysis and research application procedures. Additionally, physicians from different hospital grades displayed divergent needs for data collection (all P<0.05). Conclusions:The adoption of LLM is significantly influenced by regional disparities, institutional resources, and professional backgrounds. Implementing targeted interventions, such as enhancing technical training, optimizing LLM functionalities, and improving accessibility across diverse healthcare settings, could encourage widespread integration of LLM into clinical practice. Such measures could ultimately enhance the quality and efficiency of medical services in China and foster innovations in healthcare delivery.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.