The placenta is a temporary organ connecting the mother and fetus during embryonic development, facilitating fetal growth by transporting oxygen and nutrients and removing waste products. Placental dysfunction can lead to severe maternal and fetal complications, with potential long-term health consequences. Therefore, monitoring placental function is a critical aspect of prenatal care. Traditional clinical assessments rely on indirect methods, but functional quantitative magnetic resonance imaging (qMRI) offers a new approach. The use of qMRI enables direct evaluation of the oxygenation in the placenta and fetal organs, providing precise quantitative metrics. This technology holds promise for early detection and intervention before the onset of placental failure or fetal injury. This article reviews the latest advancements in MRI technology for evaluating placental and fetal multi-organ oxygenation.

Sesquiterpenes are natural terpenes containing 15 carbon atoms. They are widely used in the perfume, pharmaceutical, and biofuel industries due to their remarkable biological activities. The traditional production of sesquiterpenes relies on chemical synthesis or plant extraction, which has the disadvantages of low yields and waste of resources. The construction of microbial cell factories for the efficient synthesis of sesquiterpenes by means of synthetic biology provides a new option. In recent years, with the development of metabolic engineering and synthetic biology, the heterologous synthesis of a variety of sesquiterpenes has been successfully achieved by metabolic engineering of the oleaginous yeast, Yarrowia lipolytica. In this paper, we review the research progress in the heterologous synthesis of different sesquiterpenes by Y. lipolytica, discuss the synthetic biology strategies commonly used in this field, and make an outlook on the research directions and engineering approaches to further enhance the sesquiterpene yield in this host. This paper provides a reference for strategies such as synergistic optimization of synthetic biology and metabolic engineering, enhanced precursors, and opens up new directions for the application of synthetic biology in green chemistry and sustainable production.
Yarrowia/genetics* ; Sesquiterpenes/metabolism* ; Metabolic Engineering/methods* ; Synthetic Biology/methods*

The placenta is a temporary organ connecting the mother and fetus during embryonic development, facilitating fetal growth by transporting oxygen and nutrients and removing waste products. Placental dysfunction can lead to severe maternal and fetal complications, with potential long-term health consequences. Therefore, monitoring placental function is a critical aspect of prenatal care. Traditional clinical assessments rely on indirect methods, but functional quantitative magnetic resonance imaging (qMRI) offers a new approach. The use of qMRI enables direct evaluation of the oxygenation in the placenta and fetal organs, providing precise quantitative metrics. This technology holds promise for early detection and intervention before the onset of placental failure or fetal injury. This article reviews the latest advancements in MRI technology for evaluating placental and fetal multi-organ oxygenation.

Objective To investigate the molecular targets and signaling pathways involved in the therapeutic effects of Lishukang Capsule(LSK)in a rat model of high-altitude pulmonary edema(HAPE)using a proteomics-based approach.Methods A total of 60 male Wistar rats were randomly assigned to a control group,a HAPE model group,3 LSK treatment groups receiving low-,medium-,and high-dose LSK,respectively,and a Rhodiola rosea(also known as Hongjitian[HJT]in pinyin,a Chinese Romanization system)control group.After HAPE modeling,the pharmacodynamic effects were assessed and the optimal LSK dose was determined using HE stains,inflammatory cytokine quantification,lung tissue water content,and the protein concentration in bronchoalveolar lavage.Label free quantitative proteomic profiling was then applied to identify differentially expressed proteins(DEPs)in the optimal dose group,using a screening threshold of over 1.5-fold change and P<0.05.The selected DEPs were validated with Western blotting,followed by Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results The medium-dose LSK group exhibited significant anti-HAPE effects.Findings from the proteomic analysis revealed,in the comparison with the control group,267 DEPs were identified in the HAPE group.In the comparison with the HAPE group,225 DEPs were identified in the medium-dose LSK group.A total of 112 DEPs in the control group were normalized following LSK treatment in the medium-dose LSK group.In addition,GO enrichment analysis of proteins differentially expressed between the HAPE and LSK group showed that these DEPs were mainly enriched in 12 biological processes,2 cellular components,and 5 molecular functions.KEGG pathway analysis showed that LSK activated pathways associated with cell adhesion molecules,glycosaminoglycan biosynthesis,DNA replication/nucleotide excision repair,transcriptional dysregulation in cancer,and Herpes simplex virus type 1(HSV-1)infection,while inhibiting pathways associated with glycerophospholipid metabolism.Some differentially expressed proteins with potential functions were verified by Western blotting,including AGPAT5,NCAM1,SRSF3,and PLA2.These differentially expressed proteins were significantly expressed in the normal group,HAPE group,and LSK group,and the validation results were consistent with proteomic findings,indicating the high reliability of the proteomic results.Conclusion LSK exerts a significant protective effect against HAPE.Proteomic analysis suggests that its therapeutic action may be mediated through activating pathways involved in cell adhesion molecules,glycosaminoglycan biosynthesis,DNA replication/nucleotide excision repair,transcriptional dysregulation in cancer,and HSV-1 infection,alongside inhibition of pathways associated with glycerophospholipid metabolism.The key DEPs identified in these pathways may play crucial roles in the preventive and therapeutic effects of LSK on HAPE.

Autism spectrum disorder（ASD）is a multifactorial，pervasive neurodevelopmental disorder.As the morbidity rate of ASD in children increases year by year，feeding and eating behaviors，as an important and common clinical problem in children with ASD，are gaining more and more attention.Many children with ASD often have food selection issues，chewing problems，food allergy and related gastrointestinal symptoms，and even serious diseases such as eating disorders，which negatively impact on their growth and development.There are many factors affecting feeding and eating behavior problems in children with ASD，such as sensory processing，ritualistic eating behavior，gastrointestinal symptoms，age，and parenting pressure.There are also a variety of interventions that can help to improve feeding and eating behavior problems in children with ASD.Strengthening the understanding of these influencing factors and intervention treatment methods is beneficial for improving the quality of life in children with ASD.

Objective·To explore the predictive capability of retinal vascular features in preeclampsia(PE)based on artificial intelligence(AI)models.Methods·This retrospective study enrolled 789 pregnant women who registered from June 2020 to January 2021 at Shanghai First Maternity and Infant Hospital of Tongji University in the first 16 weeks of gestation.These women underwent regular prenatal examinations,had retinal fundus images captured,and delivered singleton live births at the hospital.According to whether they developed hypertensive disorders of pregnancy(HDP),they were divided into unaffected group(n=685)and HDP group(n=104).Within the HDP group,pregnancies were further categorized into gestational hypertension(GH)group(n=36)and PE group(n=68)based on the occurrence of PE.Based on the gestational age at onset,the PE group was further divided into early-onset PE group(gestational age<34 weeks)and late-onset PE group(gestational age≥34 weeks).Fundus images of the pregnant women were obtained,and an AI algorithm was utilized to diagnose retinal lesions and quantify retinal vascular features.Comparative analyses were conducted on fundus features and retinal vascular features.Univariate Logistic regression model was employed to analyze the influencing factors of PE occurrence,and multivariate Logistic regression model was further utilized to assess the correlation between retinal vascular features and the occurrence of PE.The predictive capability of retinal vascular features for PE(both early-and late-onset PE)was analyzed by using area under the curve(AUC)of receiver operator characteristic curve(ROC curve).Results·The comparative analysis of fundus features and retinal vascular features demonstrated statistically significant differences between the unaffected group and PE group in terms of central retinal artery equivalent(CRAE),central retinal vein equivalent(CRVE),arteriole-to-venular ratio(AVR),retinal artery tortuosity and retinal artery fractal dimension(all P<0.05).Univariate Logistic regression analysis indicated that second-trimester mean arterial pressure(MAP),second-trimester estimated fetal weight(EFW),CRAE,CRVE,AVR,retinal artery tortuosity and retinal artery fractal dimension were the influencing factors for PE occurrence(all P<0.05).Multivariate Logistic regression analysis revealed that second-trimester EFW,CRAE,CRVE,AVR,retinal artery tortuosity and retinal artery fractal dimension were the protective factors for the occurrence of PE,while second-trimester MAP was the risk factor for PE(all P<0.05).The analysis of ROC curves revealed that maternal risk factors along with second-trimester prenatal examination data(including MAP and EFW)and retinal vascular features model had good predictive ability for PE[AUC(95%CI)=0.784(0.725-0.843),and this model exhibited better predictive capability for early-onset PE,with an AUC(95%CI)of 0.840(0.756-0.924).Conclusion·The integration of quantified retinal vascular features based on AI models with maternal risk factors and second-trimester prenatal examination data(including MAP and EFW)enables a more effective prediction of PE occurrence,particularly early-onset PE.

Objective:To evaluate the association between polycystic ovary syndrome (PCOS)-related symptom combinations and ovarian stimulation high response in infertile patients with PCOS symptoms and controlled ovarian stimulation treatment by recombinant Human Follitropin Alfa (r-hFSHα) solution for injection, and to evaluate the efficacy and safety outcomes of using the r-hFSHα prefilled injection pen in high-risk patients with ovarian hyperstimulation syndrome (OHSS).Methods:This prospective, observational, phase Ⅳ study enrolled 1055 patients with at least one symptom/sign of PCOS using the r-hFSHα prefilled pen for over 4 months follow-up observation from December 2015 to September 2017 in the Second Hospital of Hebei Medical University, Center for Reproductive Medicine, Shandong University, Tangdu Hospital of the Air Force Military Medical University, Dalian Maternity and Child Health Care Hospital, Nanjing Maternity and Child Health Care Hospital, Jiangxi Maternity and Child Health Care Hospital, the First Affiliated Hospital of Xinjiang Medical University, the First Affiliated Hospital of Anhui Medical University, the Affiliated Hospital of Inner Mongolia Medical University. The primary endpoints assessed included the development of polycystic ovaries, elevated serum testosterone levels, menstrual cycle disturbances, development of hirsutism, and completion of egg retrieval. The efficacy endpoints of the study included the number of ocoytes retrieved, the number of M Ⅱ oocyte, the biochemical pregnancy rate, the clinical pregnancy rate, and the implantation rate. Results:In the full analysis set ( n=997), polycystic ovary rate was 54.5% (543/997), serum testosterone level was (0.4±0.2) μg/L, menstrual cycle disorder rate was 45.0% (449/997), hirsutism rate was 10.5% (105/997). The average number of oocytes retrieved after ovarian stimulation was 14.4. The clinical pregnancy rate per transfer cycle was 53.6% (251/468), the live birth rate was 45.3% (212/468), the biochemical pregnancy rate was 60.9% (285/468), the implantation rate was 39.1% (349/893), and the fresh embryo transfer cancellation rate was 24.0% (239/997). OHSS incidence was diagnosed in 1.8% (19/1054) of patients (safety set, n=1054), including 8 (0.8%) mild cases, 10 (0.9%) moderate cases and 1 (0.1%) severe case. According to the results of exploratory analysis, a decrease in body mass index (BMI) was associated with an increased risk of high response. For every 1 kg/m 2 decrease in BMI, the risk of high response (number of retrieved oocytes >15) increased by approximately 9%, the risk of high response (number of retrieved oocytes >20) increased by approximately 9%. For every 1 increase in antral follicle count (AFC), the risk of high response(number of retrieved oocytes >15) increased by approximately 6% and the risk of high response (number of retrieved oocytes >20) by approximately 4%. Conclusion:Patients with at least one symptom/sign of ovarian hyperstimulation achieved good clinical outcomes with the use of the r-hFSHα prefilled pen, and high response was associated with lower BMI and AFC.

Objective:To evaluate the association between polycystic ovary syndrome (PCOS)-related symptom combinations and ovarian stimulation high response in infertile patients with PCOS symptoms and controlled ovarian stimulation treatment by recombinant Human Follitropin Alfa (r-hFSHα) solution for injection, and to evaluate the efficacy and safety outcomes of using the r-hFSHα prefilled injection pen in high-risk patients with ovarian hyperstimulation syndrome (OHSS).Methods:This prospective, observational, phase Ⅳ study enrolled 1055 patients with at least one symptom/sign of PCOS using the r-hFSHα prefilled pen for over 4 months follow-up observation from December 2015 to September 2017 in the Second Hospital of Hebei Medical University, Center for Reproductive Medicine, Shandong University, Tangdu Hospital of the Air Force Military Medical University, Dalian Maternity and Child Health Care Hospital, Nanjing Maternity and Child Health Care Hospital, Jiangxi Maternity and Child Health Care Hospital, the First Affiliated Hospital of Xinjiang Medical University, the First Affiliated Hospital of Anhui Medical University, the Affiliated Hospital of Inner Mongolia Medical University. The primary endpoints assessed included the development of polycystic ovaries, elevated serum testosterone levels, menstrual cycle disturbances, development of hirsutism, and completion of egg retrieval. The efficacy endpoints of the study included the number of ocoytes retrieved, the number of M Ⅱ oocyte, the biochemical pregnancy rate, the clinical pregnancy rate, and the implantation rate. Results:In the full analysis set ( n=997), polycystic ovary rate was 54.5% (543/997), serum testosterone level was (0.4±0.2) μg/L, menstrual cycle disorder rate was 45.0% (449/997), hirsutism rate was 10.5% (105/997). The average number of oocytes retrieved after ovarian stimulation was 14.4. The clinical pregnancy rate per transfer cycle was 53.6% (251/468), the live birth rate was 45.3% (212/468), the biochemical pregnancy rate was 60.9% (285/468), the implantation rate was 39.1% (349/893), and the fresh embryo transfer cancellation rate was 24.0% (239/997). OHSS incidence was diagnosed in 1.8% (19/1054) of patients (safety set, n=1054), including 8 (0.8%) mild cases, 10 (0.9%) moderate cases and 1 (0.1%) severe case. According to the results of exploratory analysis, a decrease in body mass index (BMI) was associated with an increased risk of high response. For every 1 kg/m 2 decrease in BMI, the risk of high response (number of retrieved oocytes >15) increased by approximately 9%, the risk of high response (number of retrieved oocytes >20) increased by approximately 9%. For every 1 increase in antral follicle count (AFC), the risk of high response(number of retrieved oocytes >15) increased by approximately 6% and the risk of high response (number of retrieved oocytes >20) by approximately 4%. Conclusion:Patients with at least one symptom/sign of ovarian hyperstimulation achieved good clinical outcomes with the use of the r-hFSHα prefilled pen, and high response was associated with lower BMI and AFC.

Objective:To explore the teaching effect of 12-lead electrocardiogram (ECG) interpretation based on self-drawing method.Methods:This study recruited 489 students from 10 classes of clinical medicine major of Shandong Medical College as research objects. They were divided into control group and experimental group. Theoretical teaching and traditional practical training were adopted to the control group while theoretical teaching and self-drawing method were adopted to the experimental group. The ECG test scores, the number of students with excellent performance and the ECG scores of the final exam were compared between the two groups. Questionnaires were issued to assess the effect of different teaching methods on students. SPSS 25.0 was used for t test and chi-square test. Results:Compared with the experimental group, the results of the ECG special test, the number of excellent students and the ECG scores of the final exam in the control group all decreased, and the difference was statistically significant ( P<0.01). The results of the questionnaire showed that the experimental group had higher mastery of ECG abnormal patterns, learning initiative, self-confidence and better satisfaction with the overall teaching of ECG ( P<0.01). Conclusion:The practical training based on self-drawing method can improve ECG interpretation skills, learning initiative and self-confidence of students, which has achieved good teaching effect.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.