Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

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.

Purpose: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. Materials and Methods: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. Results: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. Conclusion Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Objective To explore the needs of community pharmacy services in elderly hypertensive patients in the community, especially empty-nest elderly patients. Methods Elderly hypertensive patients living in Ouyang street were randomly selected and divided into empty-nest and non-empty-nest groups by cluster random sampling method. The basic information of the respondents, the frequency of hypertension monitoring, the taking of hypertensive drugs, and the taking of other drugs were compared and analyzed. Results In term of “blood pressure monitoring frequency”, the daily pressure measurement of the empty-nest group and the non-empty-nest group accounted for 33.6% and 19.3%, respectively. There was significant difference between the two groups (P<0.05).In term of “the varieties of hypertension drugs” and taking 3 kinds of hypertension drugs at the same times, the empty-nest group accounted for 28.8% and the non-empty-nest group accounted for 16.7%, and the difference between the two groups was significant (P<0.05)；In term of “the varieties of drugs” and taking 1-2 kinds of Chinese patent drugs at the same time, the empty-nest group accounted for 39.6% and the non-empty-nest group accounted for 26.0% , and the difference between the two groups was significant (P<0.05)。Conclusion Community elderly patients with hypertension, especially empty-nest elderly patients have an urgent need for community pharmacy services，Community pharmacy services personnel should provide personalized and targeted medication education and guidance to elderly patients, especially empty-nest elderly patients, to promote the rational drug use in elderly patients.

Objective:To analyze the advantages of the impact of physical activity management under medical supervision on body components and healthy physical fitness.Methods:A total of 106 healthy adults who participated in physical activity management activities in the Health Management Center of Sichuan Academy of Medical Sciences & Sichuan Provincial People′s Hospital from April 1 st 2020 to May 31 th 2021 were enrolled. The subjects were equally divided into a medical supervision group and a self-supervision group with random number table. Both groups performed a 8-week physical activity intervention, followed by the model of “a combination of online home physical activity with offline team exercise, and team exercise interaction with individual physical activity guidance”, while health education was provided and wearable devices were worn to collect exercise data. The medical supervision group completed the set number of exercises under the supervision of the team, with on-site exercise guidance. They were required to participate in weekly one-to-one on-site instruction. The self-management group carried out exercises and participated in weekly one-to-one instruction in accordance according to their own will with online feedback. During the study, 6 cases withdrew, and 52 cases in the supervision group and 48 in the self-management group were obtained. The t and Wilcoxon tests were used to compare the body components and physical fitness of the two groups before and after intervention. Results:The amount of exercise in the supervision group was significantly higher than that in self-management group (1 359 vs 615), and there was no significant differences in exercise intensity (mean heart rate, maximum heart rate and exercise duration) between the two groups (all P>0.05). After the intervention, the body weight, body mass index (BMI), percent body fat, subcutaneous fat area and strength fitness of the supervision group were significantly lower than those before the intervention [(55.36±6.37) vs (56.11±6.33) kg, (21.48±2.85) vs (21.73±2.47) kg/m 2, (27.38±5.34) % vs (28.53±4.99) %, (119.56±48.45) vs (128.70±50.10) cm 2, (24.48±6.37) vs (26.07±5.29) kg], while the cardiorespiratory endurance, flexibility fitness and agility fitness were significantly higher [(33.57±5.06) vs (30.32±4.59) ml·kg -1·min -1, (14.71±7.51) vs (10.54±7.54) cm, (0.44±0.08) vs (0.48±0.05) s] (all P<0.05). After the intervention, the body weight, muscle mass and lean body mass in self-management group were all significantly higher than those before the intervention [(56.83±8.09) vs (56.45±8.22) kg, (38.28±3.19) vs (38.24±5.17) kg; (40.80±4.16) vs (40.32±4.95) kg], and agility fitness was significantly lower [(0.64±0.39) vs (0.49±0.05) s] (all P<0.05). It was also found that improvements regarding the following three indicators were more significant in the supervision group: visceral fat, balance and agility fitness (all P<0.05). Conclusions:Physical activity intervention under medical supervision can significantly improve the body components and physical fitness in healthy adults, as well as exercise compliance and validity.

Objective: To investigate risk factors and epidemiological characteristics of bacillary dysentery outbreaks in three schools, and to provide scientific basis for the prevention and control of the epidemic in the future. Methods: Case definition was established. All suspected, possible and confirmed cases of all students and faculty members from 3 schools (A, B, C) were selected for epidemiological investigation. Control group was used for case-control analysis, and relevant samples were collected for laboratory testing. Results: A total of 132 cases were found in 3 schools, all of which were from students, with the incidence rate of 17.74%. The morbidity in kindergarten A was 20.00%, in center primary school B it was 21.74%, and in junior middle school C it was 11.61%. Cohort studies and casecontrol studies suggested that schools are exposed places and that washing hands with raw water in schools was possible risk factor [OR(95%CI) =4.50(1.01-20.11)]. Nine stool samples were tested in laboratory, among which 8 were positive for Shigella(88.99%), and Shigella was detected in the end nodes of school s pipeline network, the water samples from canteen bucket, and the floor drains of sewer pipe. Conclusion The bacillary dysentery outbreaks in 3 schools was caused by Shigella, which may be due to fecal contamination of domestic water in 3 schools before the start of the school year. It is suggested to strengthen the management of centralized water supply and construction in rural areas, intensify the supervision at all levels, and sanitation and disinfection before school opens at all levels.

Wolfiporia cocos (F. A. Wolf) has been praised as a food delicacy and medicine for cen-turies in China. Here, we present the genome and transcriptome of the Chinese strain CGMCC5.78 of W. cocos. High-confidence functional prediction was made for 9277 genes among the 10,908 total predicted gene models in the W. cocos genome. Up to 2838 differentially expressed genes (DEGs) were identified to be related to sclerotial development by comparing the transcriptomes of mycelial and sclerotial tissues. These DEGs are involved in mating processes, differentiation of fruiting body tissues, and metabolic pathways. A number of genes encoding enzymes and regulatory factors related to polysaccharide and triterpenoid production were strikingly regulated. A potential triter-penoid gene cluster including the signature lanosterol synthase (LSS) gene and its modified compo-nents were annotated. In addition, five nonribosomal peptide synthase (NRPS)-like gene clusters, eight polyketide synthase (PKS) gene clusters, and 15 terpene gene clusters were discovered in the genome. The differential expression of the velevt family proteins, transcription factors,carbohydrate-active enzymes, and signaling components indicated their essential roles in the regu-lation of fungal development and secondary metabolism in W. cocos. These genomic and transcrip-tomic resources will be valuable for further investigations of the molecular mechanisms controlling sclerotial formation and for its improved medicinal applications.

Objective To investigate the relationship of TNF-αgene promoter 308 locus(TNF-α-308)polymorphism with the susceptibility and severity of central venous catheter-related sepsis(CRS). Methods One hundred and five CRS patients admitted in Kaihua People's Hospital from January 2015 to May 2017 were enrolled in the study.According to whether complicated with multiple organ dysfunction syndrome(MODS), they were divided into CRS complicated MODS group(n=34)and CRS non-MODS group(n=71).Meanwhile,210 patients with no catheter-related infection(case control group)and 105 healthy subjects(healthy control group)were also enrolled in the study.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to genotype TNF-α-308, and the relationship of TNF-α-308 polymorphism with the susceptibility and severity of CRS was investigated.SPSS 16.0 was used to analyze the data.Results There were no significant differences in frequencies of GG, GA,AA genotypes and G,A allele of TNF-α-308 among CRS group,case control group and healthy control group(χ2=2.262 and 0.907,both P>0.05).Compared with CRS non-MODS group,case control group and healthy control group, the frequency of GG genotype was significantly lower and the frequencies of genotype GA and AA of TNF-α-308 were significantly higher in CRS MODS group(χ2=8.809,7.700 and 9.220,all P<0.05).Compared with CRS non-MODS group,case control group and healthy control group, the allele frequencies of G were significantly lower and allele frequency of A allele of TNF-α-308 was significantly higher in CRS MODS group(χ2=9.823, 8.624 and 7.654, all P<0.05).There were no significant differences in genotype frequency and allele frequencies of TNF-α-308(χ2=0.852 and 0.975, both P>0.05)among CRS non-MODS group and case control group,healthy control group(χ2=1.022 and 0.535,both P>0.05).The odds ratio of GA +AA genotype and A allele of TNF-α-308 in CRS MODS group were 2.664(95%CI 1.259-5.639)and 2.440(95%CI 1.326-4.490).Conclusion TNF-αgene promoter 308 locus polymorphism is not a predisposing factor for CRS, but may be associated with complication of MODS in CRS patients.

Objective To investigate the effect of lower thoracic epidural block on intestinal epithelial cell apoptosis during hemorrhagic shock and resuscitation in rats.Methods Sixty-four male SD rats placed with lower thoracic epidural catheter were randomly divided into four groups (n=1 6 each):group Sham (sham operation),group HSR (hemorrhagic shock and resuscitation),group NS (hemorrhagic shock and resuscitation+epidural saline 100 μl/kg),and group TEA (hemorrhagic shock and resuscitation+epidural 0.075% ropivacaine 100 μl/kg).The hemorrhagic shock was made described by Chaudry.Rats were resuscitated by transfusing shed blood and normal saline 60 min after hemorrhagic shock.Malondialdehyde (MDA)content,superoxide dismutase (SOD)activity, and protein expression of Bax and Bcl-2 in intestinal epithelium were detected,and epithelial apoptosis index was calculated at 2 h after resuscitation.Results Compared with group Sham,intestinal epithe-lial MDA,Bax expression and epithelial apoptosis were significantly increased,while SOD activity were markedly decreased in groups HSR,NS and TEA (P<0.05).Compared with groups HSR and NS,intestinal epithelial MDA,Bax expression and epithelial apoptosis were significantly decreased, while SOD activity and Bcl-2 expression were markedly increased in group TEA (P <0.05 ). Conclusion Lower thoracic epidural block can enhance the antioxidant and anti-apoptotic ability,and inhibit the oxidative stress and cell apoptosis of intestinal epithelium.Therefore,it can promote the survival rate after hemorrhagic shock and resuscitation through protecting intestinal barrier.

Objective To investigate the current situation of maternal breastfeeding after the childbirth in Shanghai and analyze its influencing factors, so as to improve breastfeeding.Methods In this study, longitudinal follow-up and questionnaire designed based on the hospital were carried out on pregnant women at the outpatient department in eight baby-friendly hospitals of Shanghai from October 2015 to January 2016. The questionnaires included demographic characteristics and their prospective feeding method after the childbirth. Pregnant women were followed up until the delivery was finished. At the time of hospitalization discharge,they were given the 2nd questionnaire containing the basic situation after the delivery and the actual breastfeeding behavior situation.Results The rates of pregnant women with the intention of breastfeeding and exclusive breastfeeding during the third trimester were 82.5% and 82.3% respectively. After the delivery,56.4% (399/707) of mothers were breastfeeding. Binary logistic regression analysis showed that,for primipara group, breastfeeding behavior after the delivery was related to five factors:the breastfeeding intention in third trimester, age,household register,the time of onset of lactation and whether the baby was in the care unit;for multiparas group,breastfeeding behavior was related to two factors:the time of onset of lactation and whether the baby was in the care unit.Conclusions Health care workers should attach importance to the promotion of breastfeeding during pregnancy for primipara group and pay attention to the health education of the mothers with registeredpermanent residence of Shanghai. During the hospitalization,health care workers should strictly implement the "early sucking,early contact" as the baby-friendly hospital required,strengthen the breastfeeding knowledge and skill training for mothers whose babies are in the maternal care unit,ensure the normal lactation of mothers without their babies so as to improve the early breast-feeding rate after the delivery.