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 provide a reference for safe drug use in clinic. METHODS ADE reports related to nilotinib from the first quarter of 2007 to the fourth quarter of 2022 were collected from the US FDA adverse event reporting system database. The reporting odds ratio （ROR） and proportional reporting ratio （PRR） of disproportionality measures were used to mine potential ADE signals，which were compared with drug instruction and related case report， and were screened and analyzed according to the designated medical events （DME） list formulated by the European Medicines Agency. RESULTS Totally 23 332 cases of ADE with nilotinib as the primary suspected drug were reported. A total of 359 positive signals were obtained，involving 24 system organ classes （SOC），mainly concentrated in various examinations，heart organ diseases，vascular and lymphatic diseases，all kinds of nervous system diseases，etc. Among them，ADEs such as vertebral artery stenosis，coronary artery stenosis，arterial disease，liver infection and the second primary malignant tumor were not mentioned in the instructions. Seven DMEs were detected，of which bone marrow failure，pulmonary hypertension and deafness were not mentioned in the drug instruction. CONCLUSIONS The common ADE signals of nilotinib excavated in this study are consistent with the instructions. In clinical use，special attention should be paid to DME not mentioned in the instructions such as bone marrow failure，pulmonary hypertension and deafness； cardiac function， blood glucose and blood lipid indexes should be monitored closely.

Objective:To describe the reconstruction of palmar soft tissue defect of digit using dorsal digital flaps including double dorsal branches of the proper palmar digital nerves (DBPPDN) and report the results of the application of the flaps.Methods:From May, 2005 to April, 2019, a retrospective study was conducted on 113 digits of 113 patients who had palmar soft tissue defects in single digit treated with 4 types of dorsal digital flaps with bilaterally DBPPDN. Flap types: ① Modified cross-digit flap in 29 digits of 29 cases; ②Dorsal digital flap based on the dorsal branch of proper palmar digital artery (DBPPDA) in 43 digits of 43 cases; ③First dorsal metacarpal artery flap in 23 digits of 23 cases; ④ Free dorsal digit flap in 18 digits of 18 cases. In control group, single-innervated flap was used for repair of the defects, only one of injured proper palmar digital nerves on both sides was repaired with DBPPDN. Static TPD, VAS and patient satisfaction of the injured digits were evaluated by means of outpatient follow-up. The t test was applied to compare the 2 groups in relation to the quantitative outcomes. P<0.05 was considered statistically significant. Results:In the dual-innervated flap group, flap ischemia was shown in 11 digits and venous congestion was noted in 7 digits. Partial necrosis was noted in 9 flaps and healed without surgical intervention. In the dual-innervated and single-innervated flap groups, the mean static TPD were (6.92±0.12) mm and (8.92±0.20) mm, the score of VAS were (0.46±0.08) and (1.11±0.28), and patient satisfaction were (4.45±0.06) and (4.00±0.16). Significant difference was found between the 2 groups in static TPD, VAS and patient satisfaction. Dual-innervated flaps presented better discriminatory sensation on the flap ( P<0.01) and lower pain incidence ( P=0.0032) and higher patient satisfaction ( P=0.0014). Conclusion:The 4 types of dual-innervated flap are useful in reconstruction of palmar soft tissue defects of digits, especially in prevention of neuropathic pain.

Objective:To report our experience of treating open comminuted limb fractures caused by gunshots using the Masquelet technique.Methods:Between January 2016 and July 2018, 3 patients were admitted to Institute of Orthopedics, 920 Hospital of Joint Logistic Service of People's Liberation Army for open comminuted limb fractures caused by gunshots.They were all male, aged from 18 to 41 years (average, 30.7 years).Their fractures were complicated with perforating wounds and belonged to Gustilo type ⅢB for open fractures.The bone defects were 5 to 9 cm in length (average, 6.7 cm), located at the proximal femur in 2 cases and at the upper middle humerus in one.They were treated by standard Masquelet technique at 2 stages.The postoperative functions of the hip, knee and shoulder were evaluated according to the Harris hip score, Lowa knee score and Constant-Murley shoulder function score.Results:The 3 patients obtained an average follow-up of 17.3 months.The bone defects were all repaired in the 3 patients without any signs of infection.The 2 patients with femoral defects were rated as both excellent by the Harris hip score, as excellent in one and as good in the other by the Lowa knee score; the patient with humeral defects was rated as excellent by the Constant-Murley shoulder function score.Conclusion:Masquelet technique is a desirable treat-ment of segmental long bone defects caused by gunshots.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients’ physical condition.

Objective To investigate the mediating effects of neurotic personality between parental rearing patterns and depressive symptom.Methods Using multistage sampling method,982 town middle-school students were surveyed by the Symptom Checklist 90(SCL-90),the Egna Minnen av Barndoms Uppfostran (EMBU),the Eysenck Personality Questionnaire (EPQ).Correlation and regression analysis,mediating effect test,and structural equation model were constructed.Results ①)Depressive symptom (D) (1.73 ± 0.72) was significantly associated with Neurotic personality (N) (51.50± 11.37) and parental rearing patterns (r=-0.138-0.582,P＜0.01).②N,mother's rejection and deny(M3),father's emotional warmth and understanding(F1),father's over-protection(F6) had a direct effect on D,which can explain 41.6％ of the variance.F1,F6,mother's over-interference and over-protection(M2),M3 had a direct effect on N,which can explain 15.3％ of the variance.The mediating effect of N between F1,F6,M2 and D were significant(95％CI =-0.212--0.069,-0.351--0.233,0.414-0.480).③The explanation for D was 41.3％.N had completely mediating effect between M2 and depressive symptom.N had partial mediating effect between F1,F6 and D,and the proportion was 43.6％ and 49.1％.Conclusion Neurotic personality plays a mediating role between parental rearing patterns and depressive symptom in middle-school students.

Objective To investigate the clinical significance and difference in the expression of endostatin and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) patients with different response to recombinant human endostatin (rh-endostatin) combined with chemotherapy.Methods Serum levels of endostatin and VEGF in peripheral blood of 30 patients with stage Ⅳ NSCLC (NSCLC group) and 30 healthy controls (control group) were determined by enzyme-linked immunosorbent assay.Two cycles of chemotherapy combined with rh-endostatin were provided to NSCLC patients to evaluate the efficacy of the regimen.Simultaneously,serum levels of endostatin and VEGF were measured before and after treatment.Results The level of serum endostatin was (37.96 ± 9.01) ng/ml and (40.12 ± 12.11)ng/ml in NSCLC patients and healthy controls,respectively,which was lower in the former than that of the latter,without statistical difference (P ＞ 0.05).Furthermore,the level of serum VEGF was (127.98 ± 33.88) pg/ml and (36.33 ± 15.43) pg/ml in NSCLC patients and healthy controls,respectively,which was higher in the former than that of the latter,with statistical difference (t =13.48,P ＜ 0.05).Besides,levels of endostatin and VEGF in serum were not correlated with the sex,age,tumor pathological type and differentiation of NSCLC patients (P ＞ 0.05).After two cycles of chemotherapy combined with rh-endostatin treatment,the level of serum endostatin in partial response (PR) or stable disease (SD) patients was (76.22 ± 20.41) ng/ml,higher than that of progressive disease (PD) patients,which was (31.24 ± 13.09) ng/ml (t =7.143,P ＜ 0.05).In addition,the level of serum VEGF in PR or SD patients was (93.28 ± 21.33) pg/ml,which was lower than (155.81 ± 48.38) pg/ml of the PD patients (t =3.503,P ＜ 0.05).Conclusions The levels of endostatin and VEGF are associated with the efficacy of anti-angiogenesis combined with chemotherapy in NSCLC patients.

Objective To evaluate surgical treatment of chronic tibial osteomyelitis of Cierny-Mader type Ⅳ with Ilizarov technique and lesion osteotomy. Methods From January 2010 to May 2016, 39 patients with chronic tibial osteomyelitis of Cierny-Mader type Ⅳ were treated at our center. They were 33 males and 6 females, 8 to 54 years of age (average, 33.8 years). After debridement and lesion osteotomy, the tibia was fixated with Ilizarov external fixator. Bone was transported to the bone defect after corticotomy was performed on the proximal and/or distal tibial metaphyses simultaneously. Bifocal corticotomy was per-formed in 11 cases, proximal corticotomy in 21 cases, and distal corticotomy in 7 cases. The transport began 3 to 5 days after operation at a speed of 0.5 to 1.0 mm/d initially. The speed was lowered according to the bone healing and pain. Radiographic examination was done every 2 weeks to observe transporting deviation and osteogenesis in the transporting area. The transporting was adjusted whenever any abnormality was observed. The bone transporting lasted for 50 to 130 days (average, 62.4 days). Results The patients were fol-lowed up for 11 to 49 months (average, 21 months). All the soft tissue wounds healed uneventfully and there was no relapse of osteomyelitis. The bone defects in the 32 cases were reconstructed primarily. Nonunion of fracture ends happened in 5 cases and nonunion of the bone lengthening zone in 2 cases. The 7 cases of nonunion were healed after secondary bone grafting. Malalignment happened in 5 cases, 4 of which responded to timely adjustment of the external fixation and one of which had to receive secondary bone grafting after failure in adjustment of the external fixation. Ankle joint dysfunction occurred in 7 cases, 5 of which re-sponded to functional exercise and 2 of which accepted joint dysfunction because they refused surgery after unsatisfactory functional exercise. Pin tract infection of different severities occurred in 9 cases, one of which was treated by replacement of the K-wires under local anesthesia and the other 8 of which responded to rein-forced dressing change. Conclusions Chronic tibial osteomyelitis of Cierny-Mader typeⅣcan be treated by Ilizarov technique and lesion osteotomy. However, the Ilizarov technique should be improved because of the risks of multiple complications which can be reduced significantly by strengthening postoperative instruction, nursing, and regular follow-up.

Objective To evaluate the clinical outcome of reconstruction of the superior peroneal retinaculum (SPR) by using a portion of Achilles’s tendon and suture anchors in the treatment of chronic peroneal tendon dislocation .Methods Seven patients in our hospital from January 2010 to January 2015 who underwent surgical reconstruction of SPR by using a portion of Achilles ’ s tendon and suture anchors were evaluated .The ankle ’ s range of motion ( ROM) and The American Orthopaedic Foot and Ankle Society ( AOFAS) ankle-hindfoot score were used to evaluate the clinical outcome .Results All 7 cases were followed up for 6 to 24 months,the average time was 14 months,with-out recurrence.The ankle’s ROM improved from (23.6 ±1.9) °preoperative to (30.0 ±1.5) °at the final follow-up,and the AOFAS An-kle Hindfoot Scale improved from (60.6 ±3.6) point preoperative to (93.6 ±3.9) point at the final follow-up.Conclusion Surgical re-construction of SPR by using a portion of Achilles ’ s tendon and suture anchors may be an effective alternative surgical method for chronic peroneal tendon dislocation .