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

Objective:To construct the evaluation index system of core competence of extracorporeal membrane oxygenation (ECMO) specialist nurses.Methods:Through literature search and analysis, an entry pool of the core competence evaluation index system for ECMO specialist nurses was initially formed, and 20 medical and nursing experts in acute and critical care and cardiovascular fields were selected for two rounds of correspondence from September to November 2022. According to experts' opinions, the evaluation indexes of core competence of ECMO specialist nurses were modified, and the analytic hierarchy process determined the weights of indexes at all levels.Results:A total of 20 questionnaires were sent out and 20 valid questionnaires were collected during each of the two rounds of expert correspondence consultation, with effective recovery rates of 100.00%. The expert authority coefficient of the second round was 0.86, and Kendall's harmony coefficient was 0.31 ( P<0.01). Finally, the evaluation index system of core competence of ECMO specialist nurses included five primary indexes (clinical professional ability, communication and collaboration ability, nursing management ability, critical thinking ability, and professional development ability), 15 secondary indexes, and 53 tertiary indexes. Conclusions:The evaluation index system of core competence of ECMO specialist nurses constructed in this study is scientific and practical, providing a reference for evaluating ECMO specialist nurses' core competence.

Objective:To explore the factors affecting and improvement recommendations about the congealing temperature of benzyl benzoate as pharmaceutical excipient by the method in the Chinese pharmacopoeia.Methods:The influence of seven factors such as measuring device,sample size,melting temperature,condensation tempera-ture,stop stirring time,stirring frequency and reading of congealing temperature on the determination of congealing temperature of benzyl benzoate was investigated.Results:The key factor for determination of benzyl benzoate con-gealing temperature was the stop stirring time,which was more reasonable when the sample temperature drops to constant or starts to rise slightly was reasonable.Conclusion:The improved method has better accuracy and repeat-ability,and is suitable for the measuring the congealing temperature of pharmaceutical excipient benzyl benzoate.

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*

Objective:To analyze the clinical adverse events of the first carbon ion therapy system in radiotherapy for cancer patients in China.Methods:A retrospective analysis was conducted on the clinical trial monitoring data of the carbon ion therapy system obtained by the Pharmacovigilance Center of Gansu Province. A descriptive study was conducted on the demographic characteristics, radiotherapy techniques, irradiation site and dose parameters, postoperative follow-up, and adverse event information of 46 tumor patients who received carbon ion therapy and participated in the clinical trial in Wuwei Cancer Hospital, Gansu Province from November 2018 to February 2019. Frequency and percentage were used to describe and analyze the occurrence of adverse events after carbon ion therapy for cancer patients in different groups. All subjects who received radiotherapy were grouped according to the treatment dose and fractionation method.Results:The median age of the 46 patients was 47 years old, and the male to female ratio was 30∶16. There were 15, 5, 8, 9, and 9 patients with head and neck, chest, abdomen, pelvic cavity, and limb spinal tumors, respectively. The total duration of radiotherapy was 2-4 weeks for 10-16 times. There were 246 adverse events in 45 cases, with an incidence of 98%. No severe adverse events occurred. The adverse events definitely related to carbon ion devices accounted for 19.1%, and no severe adverse events related to carbon ion devices occurred. According to the evaluation criteria of common terminology criteria for adverse events (CTCAE), the main adverse events were CTCAE grade 2 and below, with only 1 (2%) head and neck tumor patient (nasopharyngeal malignant tumor) experienced CTCAE grade 3 adverse events after treatment. In addition, 43 patients developed acute adverse reactions, with an incidence of 93%, mainly involving the skin, mucosa, eyes, ears, pharynx and esophagus, upper gastrointestinal tract, lower gastrointestinal tract (including pelvic cavity), lung, genitourinary tract, heart, central nervous system and hematology (white blood cells, platelets and neutrophils), etc. Conclusion:The adverse reactions of patients treated with the first carbon ion therapy system are mainly CTCAE grade 2 and below, and the clinical adverse events are mild and controllable.

OBJECTIVE To compare the effects of individualized parenteral nutrition versus pre-mixed parenteral nutrition on liver function of patients with acute kidney injury （AKI）. METHODS Totally 97 AKI patients in the intensive care unit of our hospital from January 2021 to March 2022 were collected and randomly divided into pre-mixed multi-chamber bag （MCB） group （48 cases） and compounded parenteral nutrition （COM） group （49 cases）. The patients in both groups were given routine treatment to correct the reversible cause in time， and parenteral nutrition support treatment was started within 48 hours after the fluid resuscitation was successful or the hemodynamics of low-dose vasoactive drugs were stable. MCB group was given one bag of Fat emulsion amino acid （17） glucose （11%） injection， intravenous infusion， once a day； COM group was given Medium/long chain Fat emulsion injection （C8-24Ve） 0.5-0.8 g/kg+Compound amino acid 18AA-Ⅶ 1.0-1.2 g/kg+Glucose injection 1.5-2.5 g/kg+one Water soluble vitamin injection+Fat-soluble vitamin injection （Ⅱ） 10 mL+Multiple trace element injection （Ⅱ） 10 mL+ individualized supplement of sodium chloride and potassium chloride， with a ratio of glucose to lipid of 5∶5 and a ratio of heat to nitrogen of 100∶1. The treatment course of both groups lasted for 7 days. The percentage of abnormal liver function， the levels of liver function indexes [alanine aminotransferase （ALT）， total bilirubin （TBIL）， aspartate transaminase （AST）]， albumin （ALB）， interleukin-6 （IL-6） and C-reactive protein （CRP） were observed in 2 groups before and after treatment. RESULTS After treatment， the ratio of liver dysfunction， the levels of ALT， AST and CRP in MCB group were significantly higher than before treatment； the ratio of liver dysfunction， the levels of ALT and CRP in MCB group were significantly higher than COM group （P＜0.05）. There were no statistical significance in the ratio of liver dysfunction， the levels of ALT， AST， TBIL and CRP in COM group before and after treatment （P＞0.05）. CONCLUSIONS Individualized parenteral nutrition support treatment can reduce the occurrence of liver injury and improve the nutritional status of AKI patients.

At present, heavy ion is an ideal radiation for cancer treatment, and carbon ion is used in the treatment of many kinds of cancer due to its higher relative biological effect value. In 2019, Wuwei heavy ion center built the first medical heavy ion accelerator-carbon ion radiotherapy system in China, and obtained the registration license from the National Medical Products Administration, and officially received cancer patients in March 2020. This study introduced the development and application of the first carbon ion radiotherapy system in China.
Carbon ; China ; Heavy Ion Radiotherapy ; Heavy Ions ; Humans ; Neoplasms/radiotherapy*

Objective:To investigate the protective effect of hyperbaric oxygen therapy(HBOT)on myocardial fibrosis and oxidative stress induced by D-galactose(D-gal)in senescent model mice and its possible mechanism.Methods:Three-month-old male Kunming mice(n=27)were randomized into control, D-gal, and D-gal + HBOT groups.The control group received subcutaneous sterilized saline(5 ml · kg -1· d -1)for 8 weeks; the remaining 2 groups received subcutaneous D-gal(200 mg · kg -1· d -1)for 8 weeks. The D-gal + HBOT group underwent HBOT intervention at week 7~8.At the end of the experiment, the histopathological changes were analyzed by hematoxylin-eosin(HE)staining, and the fibrosis changes were analyzed by Masson staining and Sirius red staining.Oxidative stress kit was used to detect catalase(CAT), total superoxide dismutase(T-SOD)activity and malon-di-aldehyde(MDA)content in serum of mice.Western blotting was used to detect the expression levels of the aging-related proteins p53 and p16 in mouse heart tissue, the heart-function-related proteins atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP), and the oxidative stress-related protein superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2)and catalase(CAT). Results:Cardiac morphologic staining indicated that as compared with the control group, mice of D-gal group exhibited features of senescence and the increased fibrosis area, and senescence and fibrosis were obviously improved after HBOT intervention as compared with the D-gal group.The findings of the oxidative stress kit measurement indicated that as compared with the control group, the D-gal group had markedly decreased activities of CAT and T-SOD, significantly increased MDA content in the serum.After HBOT treatment, as compared with d-gal group, serum CAT and T-SOD activities were increased, while MDA content was decreased( F=126.85, 32.89, 157.50, all P<0.05).Furthermore, as compared with the control group, the D-gal group had obviously increased contents of p53, p16, ANP and BNP, while the content of CAT, SOD1 and SOD2 were obviously decreased.After HBOT intervention, as compared with the D-gal group, the contents of p53, p16, ANP、BNP were reduced, while the content of CAT, SOD1 and SOD2 were increased( F=36.37, 14.81, 23.28, 58.41, 12.79, 80.08, 6.63, all P<0.05). Conclusions:HBOT intervention could protects against cardiac injury in aging mice, which may be related to attenuating myocardial fibrosis, inducing the expression of antioxidant enzymes, and reducing oxidative stress.

Objective:To compare the dosimetric differences between accelerated partial breast irradiation intensity modulated radiation therapy (APBI-IMRT) and whole breast irradiation with simultaneous integrated boost intensity modulated radiotherapy (WBI-SIB-IMRT) for early-stage breast cancer after breast-conserving surgery.Methods:A total of 35 patients with early-stage breast cancer in Jilin Province Cancer Hospital between July 2009 and December 2014 after breast-conserving surgery were enrolled. The targeted regions of APBI-IMRT and WBI-SIB-IMRT were created for each patient. The dosimetric difference comparison of the targeted region and normal tissues was evaluated by using dose volume histogram (DVH).Results:There was no significant difference in the dosimetric comparison of gross tumor volume (GTVtb) and planning gross tumor volume (PGTVtb) after correction of cumulative radiation effect (CRE) between WBI-SIB-IMRT group and APBI-IMRT group (both P > 0.05). The dose of clinical target volume (CTV) and planning target volume(PTV) in APBI-IMRT group was higher than that in WBI-SIB-IMRT group [CTV: (4 720±71) cGy vs. (3 889±79) cGy, t = 3.184, P = 0.027; PTV: (4 675±164) cGy vs. (3 807±199) cGy, t = 2.751, P = 0.032] after CRE correction. Compared with WBI-SIB-IMRT group, the dose of ipsilateral lung tissue and left heart tissue in APBI-IMRT group was decreased after CRE correction [(558.5±8.9) cGy vs. (1 304.9±34.4) cGy, t = -7.328, P = 0.001; (35.5±5.3) cGy vs. (843.0±41.5) cGy, t = -8.137, P = 0.001]. V 5/3.6 Gy, V 10/7.3 Gy, V 15/10.9 Gy, V 20/14.6 Gy, V 25/18.2 Gy and V 30/21.9 Gy of the ipsilateral lung and V 30/21.9Gy, V 40/29.2Gy of left heart in all breast cancer patients after two chemotherapy treatments had significant differences (all P = 0.001). Conclusion:Compared with WBI-SIB, APBI-IMRT can improve the dose distribution in target area and reduce the volume of high dose irradiation in organs at risk.

OBJECTIVE: To observe the effect of n-hexane subchronic exposure on the serum level of neuron specific enolase(NSE), neurofilament light chain protein(NF-L) and nerve growth factor(NGF) in rat, and to explore the feasibility of using NSE, NF-L and NGF as biomarkers of n-hexane neurotoxicity. METHODS: Specific pathogen free male SD rats were randomly divided into control group and low-, medium-and high-dose exposure groups, with 6 rats in each group. Rats in the low-, medium-and high-dose exposure groups were given n-hexane solution at doses of 168, 675 and 2 700 mg/kg body mass, respectively, while rats in the control group were gavaged with 0.9% sodium chloride solution, once a day, 5 days a week for 6 weeks. At week 0, 2, 4, and 6 of exposure, the body mass of the rats was weighed, the gait scores were performed, and the serum levels of NSE, NF-L, and NGF were detected.RESULTS: Body mass, gait score and serum levels of NSE and NF-L in rats were statistically significant in terms of the n-hexane exposure dose and exposure time(P<0.01). At the 6 th week of n-hexane exposure, the body mass of the three dose exposure groups was lower than that of the control group(P<0.05), and the gait score was higher than that of the control group(P<0.05). Moreover, the abnormal gait of the rats showed a dose-effect relationship with the increasing n-hexane poisoning dose. At week 2, 4 and 6, the serum levels of NSE and NF-L in these three dose exposure groups were higher than that in the control group(P<0.05). In addition, the serum level of NF-L in rats in the medium-and high-dose exposure groups increased with the n-hexane exposure time increasing and showed a time-effect relationship(P<0.05). The level of serum NGF in rats was statistically significant in the main effects of n-hexane dose and duration of exposure(P<0.05). The serum NGF level in the high-dose exposure group was lower than that in the control group, the low-dose and medium-dose exposure groups(P<0.05). NGF level in serum of rats at week 6 was lower than that at week 0, 2 and 4(P<0.05). CONCLUSION: Both NSE and NF-L in serum can be used as biomarkers for the early effect of n-hexane on peripheral nerve injury. The feasibility of using serum NGF as a biomarker for the early effect of n-hexane on peripheral nerve injury warrants further investigation.