ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

BackgroundMany studies have shown that patients with depressive disorder show impairments in prospective memory， while it is deemed necessary for facilitating their social reintegration， and the current research findings are inconsistent regarding the factors affecting prospective memory of patients with depressive disorder. ObjectiveTo explore the impact of target characteristics （emotional valence and salience） on prospective memory in patients with depressive disorder， so as to provide references for the training and recovery of prospective memory function in these patients. MethodsFrom January to December 2022， 53 patients with depressive disorder were recruited from the outpatient department of Inner Mongolia Autonomous Mental Health Center. Meanwhile， 45 healthy individuals were concurrently recruited from surrounding communities as control group. An experiment with a 2 （participant type： depressive disorder， healthy control） ×2 （target salience： salient， non-salient） ×3 （emotional valence： positive， neutral， negative） factorial design was conducted. The positive/neutral/negative emotional pictures from Chinese Affective Picture System （CAPS） were used for emotional stimulation. A dual-task experimental paradigm was adopted， and the response time and accuracy in prospective memory task and ongoing task were recorded for participants with different target characteristics. Results①In the prospective memory task， the main effect of participant type was statistically significant， with the depressive group showing lower accuracy （F=14.892， P<0.01） and longer response time （F=10.642， P=0.002） compared with control group. ② The main effect of target emotional valence on accuracy （F=7.575， P=0.001） and response time （F=3.196， P=0.044） in the prospective memory task was statistically significant. Simple effect analysis revealed that depressive group yielded a shorter response time and higher accuracy rate under negative conditions compared with positive and neutral conditions （P<0.05 or 0.01）. ③ The main effect of target salience on accuracy （F=6.659， P=0.012） and response time （F=10.106， P=0.002） in the prospective memory task was also statistically significant， with higher accuracy and shorter response time for salient targets compared with non-salient targets. ConclusionPatients with depressive disorder demonstrate preferential attention to and processing of negative stimuli in prospective memory tasks， while increasing target salience may facilitate spontaneous processing of prospective memory task in patients with depressive disorder. ［Funded by Inner Mongolia Health Commission Medical Health Science and Technology Project （number， 202202104）］

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

Objective To evaluate the efficacy of Puerariae lobatae radix （PLR） and Anemarrhenae Rhizoma （AR） in preventing and treating Alzheimer’s disease （AD） and explore its potential mechanism of action by LC-MS serum metabolomics strategy. Methods The AD rat model was established by administering aluminum chloride （AlCl₃） and D-galactose （D-gal） for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted, and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased （P<0.05）, while the SOD content was decreased considerably （P<0.01）. The learning and memory abilities of AD model rats were improved, oxidative stress and lipid peroxidation levels were reversed, and serum SOD content was increased significantly after the intervention of PLR-AR, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified between the AD model group and the control group, mainly involving 10 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis, et.al. The intervention of PLR-AR could adjust 47 metabolites, with 20 metabolites showing significant differences （P<0.05）. The significantly adjusted metabolites involve 6 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, et al. Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways.

Objective:To investigate the risk factors associated with post-prematurity respiratory disease (PPRD) in very preterm infants.Methods:A prospective cohort study was conducted, enrolling 369 very preterm infants who were admitted to the neonatal intensive care unit of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, within one week of birth from January 2019 to June 2023. Data on maternal and infant clinical characteristics, neonatal morbidities, and treatments during hospitalization were collected. The very preterm infants were divided into 2 groups based on whether they developed PPRD. Continuous variables were compared using Mann-Whitney U test, while categorical variables were compared using χ2 tests or continuity correction χ2 test. Multivariate Logistic regression analysis was used to identify the independent risk factors for PPRD in very preterm infants. Results:Among the 369 very preterm infants, 217 cases(58.8%) were male, with a gestational age of 30 (28, 31) weeks at birth and a birth weight of 1 320 (1 085, 1 590) g. Of these, 116 cases (31.4%) developed PPRD, while 253 cases (68.6%) did not. The very preterm infants in the PPRD group had a lower gestational age and lower birth weight (both, P<0.001). The PPRD group also had a higher proportion of males, lower Apgar scores at the 1 th minute after birth and the 5 th minutes after birth, a higher rate of born via cesarean delivery, and a higher incidence of bronchopulmonary dysplasia, more pulmonary surfactant treatment, longer durations of mechanical ventilation, longer total oxygen therapy, and lower Z-score for weight at discharge (all P<0.05). Multivariate Logistic regression analysis showed that gestational age ( OR=0.85, 95% CI 0.73-0.99, P=0.037), born via cesarean delivery ( OR=2.23, 95% CI 1.21-4.10, P=0.010), a duration of mechanical ventilation ≥7 days ( OR=2.51, 95% CI 1.43-4.39, P=0.001), and a Z-score for weight at discharge ( OR=0.82, 95% CI 0.67-0.99, P=0.040) were all independent risk factors for PPRD in very preterm infants. Conclusion:Very preterm infants with a small gestational age, born via cesarean section, mechanical ventilation ≥7 days, and a low Z-score for weight at discharge should be closely monitored for PPRD, and provided with standardized respiratory management after discharge.

Objective: To understand the prevalence and related factors of depressive symptoms among primary and secondary school students in the in depth monitoring counties of China s Rural Compulsory Education Nutrition Improvement Program, so as to provide a basis for prevention and psychological intervention of depressive symptoms among children and adolescents in rural areas. Methods: In November 2022, a stratified random sampling method was adopted to collect height and weight data, basic personal and family information of 7 949 primary and secondary school students from grade three to grade nine through physical measurements and questionnaires in 56 key monitoring schools implementing the Student Nutrition Improvement Program in 7 in depth monitoring counties (Jalaid Banner in Inner Mongolia, Jinzhai County in Anhui, Mao Xian in Sichuan, Tiandeng County in Guangxi, Mian County in Shaanxi, Zhaozhou County in Heilongjiang and Youxi County in Fujian), and to obtain the information related to their depressive symptoms through the self assessment questionnaire on depression. Multivariate Logistic regression analysis was conducted to analyze the prevalence of depressive symptoms among primary and secondary school students, as well as their related factors. Results: The detection rate of depressive symptoms among primary and secondary school students in the in depth monitored counties was 23.5%. Logistic regression analysis showed that the probability of detecting depressive symptoms was higher among female students, middle school students, students whose video screen duration per day was >2 h, and students whose parents marital status was divorced or widowed ( OR =1.40, 1.64, 1.60, 1.24), and students whose sleep duration reached the recommended standard, whose parents usually accompanied them daily for time was 60-<120 min and ≥120 min, and students whose mothers literacy level was middle school graduation had lower probability of detecting depressive symptoms ( OR =0.85, 0.84, 0.71, 0.76) ( P < 0.05 ). Conclusion The detection rate of depressive symptoms among students in the in depth monitoring area is high, and targeted interventions need to be developed for students to reduce the risk of mental health problems.

Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.