OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To compare the efficacies of endovascular therapy (EVT) and standard medical therapy in acute ischemic stroke (AIS) patients aged ≥85 years, and analyze the independent influencing factors for poor prognosis of AIS patients after EVT.Methods:Sixty-nine AIS patients aged ≥85 years admitted to Department of Neurology, Xi'an Third Hospital from January 2018 to April 2024, including 40 accepted EVT and 28 accepted standard medicinal therapy, were enrolled. Modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 90 days after onset. General data, prognosis and complications between the EVT group and standard medical therapy group were compared. General data, treatment processes and complications between patients with good prognosis and poor prognosis in the EVT group were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for poor prognosis in AIS patients after EVT.Results:Compared with the standard medical therapy, the EVT group had significantly lower NIHSS score at discharge, greater improvement in NIHSS score (NIHSS score at admission-NIHSS score at discharge), lower mRS score 90 days after onset, higher good prognosis rate, lower mortality rate within 90 days of onset, and longer hospital stay ( P<0.05). In the EVT group, 11 patients (27.5%) had good prognosis and 29 patients (72.5%) had poor prognosis 90 days after onset. Compared with the good prognosis group, the poor prognosis group had significantly higher blood glucose level and lower Alberta Stroke Program Early CT Score (ASPECT) on admission ( P<0.05). Multivariate Logistic regression analysis showed that blood glucose on admission ( OR=2.363, 95% CI: 1.134-4.928, P=0.022) and ASPECT score on admission ( OR=0.273, 95% CI: 0.088-0.854, P=0.026) were independent influencing factors for poor prognosis in AIS patients after EVT. Conclusion:AIS patients aged ≥85 years received EVT have better prognosis compared with those accepted standard medical therapy; these patients with high glucose level and low ASPECT score on admission have poor prognosis.

Objective:To explore the latent profiles of work withdrawal behaviors of junior nurses and their relationship with workplace social capital.Methods:Using the convenience sampling method, from July to August 2023, 348 junior nurses from five Class Ⅲ and seven ClassⅡ public hospitals in Ningxia Hui Autonomous Region were selected as the research objects. They were investigated with a General Information Questionnaire, the Work Withdrawal Behavior Scale, and the Workplace Social Capital Scale. Latent profile analysis was used to explore the categories of work withdrawal behaviors of junior nurses, and the differences in workplace social capital levels among junior nurses of different categories were compared.Results:A total of 348 questionnaires were recovered online in this survey, and 342 questionnaires were valid, with a valid rate of 98.3%. The work withdrawal behaviors of 342 junior nurses could be divided into three latent profiles, including 246 junior nurses (71.9%) in the low psychological-low behavioral withdrawal group, 81 junior nurses (23.7%) in the high psychological-low behavioral withdrawal group, and 15 junior nurses (4.4%) in the high psychological-high behavioral withdrawal group. The results of the unordered multinomial Logistic regression analysis showed that gender, whether they love nursing work or not, the average number of night shifts per month, the workplace social capital, and working years were the influencing factors of the work withdrawal behaviors of junior nurses ( P<0.05) . There were statistically significant differences in the workplace social capital among the three categories of junior nurses ( H=83.82, P<0.01) . Conclusions:There are three categories of work withdrawal behaviors among junior nurses, and there are differences in workplace social capital among junior nurses of different categories. Nursing managers should intervene and support junior nurses according to the characteristics of different categories to improve their workplace social capital levels.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To explore the latent profiles of work withdrawal behaviors of junior nurses and their relationship with workplace social capital.Methods:Using the convenience sampling method, from July to August 2023, 348 junior nurses from five Class Ⅲ and seven ClassⅡ public hospitals in Ningxia Hui Autonomous Region were selected as the research objects. They were investigated with a General Information Questionnaire, the Work Withdrawal Behavior Scale, and the Workplace Social Capital Scale. Latent profile analysis was used to explore the categories of work withdrawal behaviors of junior nurses, and the differences in workplace social capital levels among junior nurses of different categories were compared.Results:A total of 348 questionnaires were recovered online in this survey, and 342 questionnaires were valid, with a valid rate of 98.3%. The work withdrawal behaviors of 342 junior nurses could be divided into three latent profiles, including 246 junior nurses (71.9%) in the low psychological-low behavioral withdrawal group, 81 junior nurses (23.7%) in the high psychological-low behavioral withdrawal group, and 15 junior nurses (4.4%) in the high psychological-high behavioral withdrawal group. The results of the unordered multinomial Logistic regression analysis showed that gender, whether they love nursing work or not, the average number of night shifts per month, the workplace social capital, and working years were the influencing factors of the work withdrawal behaviors of junior nurses ( P<0.05) . There were statistically significant differences in the workplace social capital among the three categories of junior nurses ( H=83.82, P<0.01) . Conclusions:There are three categories of work withdrawal behaviors among junior nurses, and there are differences in workplace social capital among junior nurses of different categories. Nursing managers should intervene and support junior nurses according to the characteristics of different categories to improve their workplace social capital levels.

Objective:To compare the efficacies of endovascular therapy (EVT) and standard medical therapy in acute ischemic stroke (AIS) patients aged ≥85 years, and analyze the independent influencing factors for poor prognosis of AIS patients after EVT.Methods:Sixty-nine AIS patients aged ≥85 years admitted to Department of Neurology, Xi'an Third Hospital from January 2018 to April 2024, including 40 accepted EVT and 28 accepted standard medicinal therapy, were enrolled. Modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 90 days after onset. General data, prognosis and complications between the EVT group and standard medical therapy group were compared. General data, treatment processes and complications between patients with good prognosis and poor prognosis in the EVT group were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for poor prognosis in AIS patients after EVT.Results:Compared with the standard medical therapy, the EVT group had significantly lower NIHSS score at discharge, greater improvement in NIHSS score (NIHSS score at admission-NIHSS score at discharge), lower mRS score 90 days after onset, higher good prognosis rate, lower mortality rate within 90 days of onset, and longer hospital stay ( P<0.05). In the EVT group, 11 patients (27.5%) had good prognosis and 29 patients (72.5%) had poor prognosis 90 days after onset. Compared with the good prognosis group, the poor prognosis group had significantly higher blood glucose level and lower Alberta Stroke Program Early CT Score (ASPECT) on admission ( P<0.05). Multivariate Logistic regression analysis showed that blood glucose on admission ( OR=2.363, 95% CI: 1.134-4.928, P=0.022) and ASPECT score on admission ( OR=0.273, 95% CI: 0.088-0.854, P=0.026) were independent influencing factors for poor prognosis in AIS patients after EVT. Conclusion:AIS patients aged ≥85 years received EVT have better prognosis compared with those accepted standard medical therapy; these patients with high glucose level and low ASPECT score on admission have poor prognosis.

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.