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 analyze the access pathway,regulatory process and payment of digital therapies in various countries,so as to provide references and materials for the development of digital therapies in China.Methods:By using literature research method,text analy-sis method and comparative analysis method,it combed domestic and international policies related to digital therapy,described the policy support status of digital therapy in each country,and comparatively analyzed the differences in the definition,regulation and payment of digi-tal therapy products in each country.Results:The US,Germany,UK,Japan,South Korea,and other countries have introduced frame-works to define,categorize,and approve digital therapies,distinguishing them from other digital health products.China also includes digital therapies in its national planning,with Hainan leading in supportive policies.Regulatory processes slightly differ by country but generally in-volve determining risk levels and conducting comparative analysis.Currently,only the UK,Germany,Japan,etc.,offer health insurance reimbursement for digital therapies.Conclusion:Internationally,there are mature policy frameworks and experiences for digital therapies,and China can learn from the international experiences,while exploring the path of digital therapies with Chinese characteristics and continue to improve the policies of digital therapies and to meet the needs of patients.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

Objective:To understand the current status, research hotspots, and future trends in the field of retinoblastoma (RB).Methods:Using the Web of Science Core Collection SSCI and SCI-Expanded as data sources, relevant RB literature from January 2015 to November 2024 was retrieved. The bibliometric analysis software CiteSpace 6.2.R6 was employed to perform visual analyses of countries/regions, institutions, journals, authors, co-cited references, and keywords.Results:A total of 5 042 relevant publications were identified. Annual publication numbers in this field consistently exceeded 400, peaking at 565 in 2021. The United States contributed the highest number of publications, with 1 600 articles (31.73%). Among institutions, Harvard University ranked first with 167 publications (3.31%). Abramson DH of Memorial Sloan Kettering Cancer Center published the most papers (75). Nature (United Kingdom) received the highest citation count (2 349). The highest betweenness centrality was observed for the United States (0.14) among countries/regions, Shanghai Jiao Tong University (0.21) among institutions, and Berry JL of Children’s Hospital Los Angeles (0.21) at the author level. Co-citation and keyword analyses revealed that RB research hotspots are shifting from a focus on basic molecular mechanisms, such as the cell cycle and RB protein, toward advanced therapeutic strategies, such as intra-arterial chemotherapy and nanoparticle-based drug delivery. Emerging keywords such as complexity, chemoresistance and carboplatin indicate that future studies will focus on optimising diagnosis and treatment. Conclusions:From 2015 to 2024, RB research displayed a sustained growth trend, with the United States and its institutions and scholars contributing the most publications. The research focus has shifted from the exploration of molecular mechanisms to the optimization of precise treatment strategies, among which the application of nanotechnology and the resolution of drug resistance mechanisms will become key breakthrough directions.

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%.

Background and Aims:CNLC stage IIIb hepatocellular carcinoma(HCC)is often accompanied by extrahepatic metastases and carries a poor prognosis.The optimal treatment strategy for these patients remains controversial,and the role of local therapy lacks robust evidence.This study aimed to compare overall survival(OS)between patients receiving combined local and systemic therapy versus systemic therapy alone,and to assess the prognostic impact of oligometastatic status and the cumulative duration of no evidence of disease(NED).Methods:A retrospective analysis was conducted on 76 CNLC stage IIIb HCC patients treated at Xiangya Hospital from January 2017 to December 2023.Forty patients received systemic therapy plus local therapy(local therapy group),and 36 received systemic therapy alone(no local therapy group).OS was compared between the two groups.Subgroup analyses were performed for oligometastatic and non-oligometastatic patients to evaluate the benefit of local therapy.In the local therapy group,the correlation between cumulative NED duration and OS was also examined.Results:The 1-,2-,3-,and 5-year OS rates were 89.0%vs.66.7%,64.3%vs.25.6%,35.3%vs.8.7%,and 8.3%vs.0.0%for the local therapy and no local therapy groups,respectively,with a statistically significant difference(P=0.003).Among oligometastatic patients,the local therapy group had significantly better OS than the no local therapy group(P=0.008),whereas no significant difference was observed in non-oligometastatic patients(P>0.05).Multivariate analysis identified oligometastases as an independent prognostic factor(HR=2.213,P=0.045).In the local therapy group,cumulative NED duration was strongly correlated with OS(r=0.851,P<0.001).Local therapy was well tolerated,with no treatment-related deaths observed.Conclusion:For CNLC stage IIIb HCC patients with well-controlled intrahepatic disease,local therapy can significantly prolong survival,particularly in those with oligometastases.Achieving and maintaining NED may represent an important therapeutic goal in this patient population.

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 analyze the access pathway,regulatory process and payment of digital therapies in various countries,so as to provide references and materials for the development of digital therapies in China.Methods:By using literature research method,text analy-sis method and comparative analysis method,it combed domestic and international policies related to digital therapy,described the policy support status of digital therapy in each country,and comparatively analyzed the differences in the definition,regulation and payment of digi-tal therapy products in each country.Results:The US,Germany,UK,Japan,South Korea,and other countries have introduced frame-works to define,categorize,and approve digital therapies,distinguishing them from other digital health products.China also includes digital therapies in its national planning,with Hainan leading in supportive policies.Regulatory processes slightly differ by country but generally in-volve determining risk levels and conducting comparative analysis.Currently,only the UK,Germany,Japan,etc.,offer health insurance reimbursement for digital therapies.Conclusion:Internationally,there are mature policy frameworks and experiences for digital therapies,and China can learn from the international experiences,while exploring the path of digital therapies with Chinese characteristics and continue to improve the policies of digital therapies and to meet the needs of patients.

Background and Aims:CNLC stage IIIb hepatocellular carcinoma(HCC)is often accompanied by extrahepatic metastases and carries a poor prognosis.The optimal treatment strategy for these patients remains controversial,and the role of local therapy lacks robust evidence.This study aimed to compare overall survival(OS)between patients receiving combined local and systemic therapy versus systemic therapy alone,and to assess the prognostic impact of oligometastatic status and the cumulative duration of no evidence of disease(NED).Methods:A retrospective analysis was conducted on 76 CNLC stage IIIb HCC patients treated at Xiangya Hospital from January 2017 to December 2023.Forty patients received systemic therapy plus local therapy(local therapy group),and 36 received systemic therapy alone(no local therapy group).OS was compared between the two groups.Subgroup analyses were performed for oligometastatic and non-oligometastatic patients to evaluate the benefit of local therapy.In the local therapy group,the correlation between cumulative NED duration and OS was also examined.Results:The 1-,2-,3-,and 5-year OS rates were 89.0%vs.66.7%,64.3%vs.25.6%,35.3%vs.8.7%,and 8.3%vs.0.0%for the local therapy and no local therapy groups,respectively,with a statistically significant difference(P=0.003).Among oligometastatic patients,the local therapy group had significantly better OS than the no local therapy group(P=0.008),whereas no significant difference was observed in non-oligometastatic patients(P>0.05).Multivariate analysis identified oligometastases as an independent prognostic factor(HR=2.213,P=0.045).In the local therapy group,cumulative NED duration was strongly correlated with OS(r=0.851,P<0.001).Local therapy was well tolerated,with no treatment-related deaths observed.Conclusion:For CNLC stage IIIb HCC patients with well-controlled intrahepatic disease,local therapy can significantly prolong survival,particularly in those with oligometastases.Achieving and maintaining NED may represent an important therapeutic goal in this patient population.

Objective:To understand the current status, research hotspots, and future trends in the field of retinoblastoma (RB).Methods:Using the Web of Science Core Collection SSCI and SCI-Expanded as data sources, relevant RB literature from January 2015 to November 2024 was retrieved. The bibliometric analysis software CiteSpace 6.2.R6 was employed to perform visual analyses of countries/regions, institutions, journals, authors, co-cited references, and keywords.Results:A total of 5 042 relevant publications were identified. Annual publication numbers in this field consistently exceeded 400, peaking at 565 in 2021. The United States contributed the highest number of publications, with 1 600 articles (31.73%). Among institutions, Harvard University ranked first with 167 publications (3.31%). Abramson DH of Memorial Sloan Kettering Cancer Center published the most papers (75). Nature (United Kingdom) received the highest citation count (2 349). The highest betweenness centrality was observed for the United States (0.14) among countries/regions, Shanghai Jiao Tong University (0.21) among institutions, and Berry JL of Children’s Hospital Los Angeles (0.21) at the author level. Co-citation and keyword analyses revealed that RB research hotspots are shifting from a focus on basic molecular mechanisms, such as the cell cycle and RB protein, toward advanced therapeutic strategies, such as intra-arterial chemotherapy and nanoparticle-based drug delivery. Emerging keywords such as complexity, chemoresistance and carboplatin indicate that future studies will focus on optimising diagnosis and treatment. Conclusions:From 2015 to 2024, RB research displayed a sustained growth trend, with the United States and its institutions and scholars contributing the most publications. The research focus has shifted from the exploration of molecular mechanisms to the optimization of precise treatment strategies, among which the application of nanotechnology and the resolution of drug resistance mechanisms will become key breakthrough directions.