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

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

Objective:To investigate the effect of flap combined with 3D printed microporous titanium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect.Methods:From January 2019 to December 2020, 2 patients with large soft tissue defects on dorsal foot together with large metatarsal bone defect and 4 patients with soft tissue defects of calf with large tibial bone defect were treated. The areas of soft tissue defect were 5.0 cm×8.0 cm-15.0 cm×10.0 cm. The length of the bone defect were 3.8 cm to 7.0 cm, 5.75 cm in average. In the first stage, metatarsal bone defect or tibial bone defect was filled with vancomycin blended bone cement, meanwhile, soft tissue defect was repaired with anterolateral femoral flap(ALTF) with vascular anastomosis in 2 cases of feet, and local fascia flap was trans-positioned in 4 cases of lower extremity defects. The sizes of repairing flap were 6.0 cm×8.5 cm-16.0 cm×11.0 cm. Two to 7 months after the initial surgery, the customer designed microporous titanium prostheses were used(5 cases with microporous titanium and 1 with microporous tantalum) to repair the bone defects. The wound healing, the integration of metatarsal and tibial fractures with 3D printed microporous titanium(tantalum) prostheses, and the walking condition were observed after surgery. The follow-up lasted from 6 to 25 months, with an average of 12.7 months.Results:The wound healing in 5 patients was good. The patients stood on the foot in 2 months after surgery, started to walk with the assistance of crutch in 3 months after surgery, and took walk without assistance in 5-6 months after surgery. Good osseous integration were achieved. One diabetic patient had infection of foot wound 3 months after surgery. After removal of microporous titanium prosthesis and replacement of vancomycin blended interstitial substance of bone cement, the wound healed and the patient resumed walking.Conclusion:It is an effective method to encourage the patients to take early ambulation after the surgery for lower extremity soft tissue defect with large bone defect that was repaired by a flap and 3D printed microporous titanium(tantalum)prosthesis. Further observations are required to investigate the long-term efficacy, and the reduction of prosthesis infection rate requires further exploration.

Objective:To investigate the clinical effects of Ilizarov external fixation combined with bone surface roughening technique in the treatment of tibial dystrophic nonunion.Methods:The data were retrospectively studied of the 11 patients with tibial dystrophic nonunion who had been treated at Department of Orthopedics, 920 Hospital of the Joint Logistic Support Force of PLA from April 2018 to January 2021. They were 7 males and 4 females, aged from 32 to 61 years (average, 44.6 years). Their last surgical fixation before admission was Hoffman Ⅱ external fixation in 6 cases and locking plate internal fixation in 5 cases. The time from their last operation to the present operation ranged from 9 to 26 months (average, 14.2 months). After treatment by Ilizarov external fixation combined with bone surface roughening technique, the 11 patients started weight-bearing walking with double crutches from the second day after operation, gradually progressed to walking with a single crutch 2 months after operation, and resumed normal weight-bearing walking without any crutch 3 months after operation.Results:All the 11 patients were followed up for 12 to 30 months (average, 20.0 months). The time for bearing Ilizarov external fixation ranged from 6 to 10 months (average, 8.6 months). Mild pin track infection occurred in 4 cases but was healed by pin track rinse with normal saline; moderate pin track infection happened in another 2 cases but responded to oral amoxicillin capsules for one week in addition to pin track rinse with normal saline. All the bone dystrophic nonunion was cured after 6 to 10 months (average, 8.6 months). By the bone criteria of Association for Study and Application of Method of Ilizarov (ASAMI), the efficacy was excellent in 8 cases, good in 2 and fair in one at the last follow-up; by the limb function criteria of ASAMI, the efficacy was excellent in 9 cases and good in 2 at the last follow-up.Conclusion:Ilizarov external fixation combined with bone surface roughening technique is an effective treatment of tibial dystrophic nonunion.

Objective:To investigate the short-term efficacy of anatomical calcaneal external fixator in the treatment of calcaneal fractures.Methods:A retrospective study was conducted of the 9 patients with calcaneal fracture who had been admitted to Department of Orthopedics, 920 Hospital of the PLA Joint Logistics Support Force between September 2019 and March 2020. There were 7 males and 2 females, aged from 23 to 66 years (mean, 41.3 years). The injury was caused by a fall from a height in 6 cases and a traffic accident in 3 cases. By the Sanders classification, there were 2 cases of type ⅡB, 2 cases of type ⅢAC, 3 type Ⅲ AB, one of type Ⅲ BC and one type Ⅳ. By the AO grading for closed soft tissue injury in the 8 closed fractures, there were 5 cases of grade Ⅰ and 3 cases of grade Ⅱ. The one open fracture was type ⅢB by the Gustilo-Anderson classification and treated with skin flap repair after debridement. All the 9 patients were treated with an anatomic calcaneal external fixator during stage-one or stage-two surgery (8 patients in stage-one and one in stage-two). The fracture union time for the patients was recorded; the ankle and hindfoot score of American Orthopedic Foot and Ankle Society (AOFAS) and the protocol of Association for the Study and Application of the Method of Ilizarov (ASAMI) were used at the last follow-up to assess the short-term efficacy.Results:Postoperative follow-up for the 9 patients ranged from 6 to 18 months (mean, 9.8 months). The duration of fracture union in the 9 patients ranged from 2 to 4 months (mean 2.8 months). The AOFAS ankle and hindfoot score at last follow-up ranged from 79 to 93 points (mean, 84.7 points) for the male patients (6 excellent and one good), and from 82 to 91 points (mean, 86.5 points) for the female patients (one excellent and one good). According to the ASAMI protocol at last follow-up, the short-term efficacy was rated as excellent in 6 cases, as good in 2 cases and as fair in one. The patients with closed fracture could get out of bed for rehabilitation on day 3 after surgery. None of the patients experienced such complications as pin tract infection and osteomyelitis during follow-up.Conclusion:The anatomic external calcaneal fixator demonstrates fine short-term efficacy in the treatment of calcaneal fractures, due to its advantages like anatomical configuration, a limited number of implants, and a possibility of partial weight-bearing for exercises on the third postoperative day.

Objective:To explore the treatment of pressure sores in different parts of the buttocks.Methods:From May, 2005 to March, 2020, 170 (157 patients) pressure sores in different parts of buttocks were treated. Eighty-two pressure sores located at sacrococcyx, 52 at ischial tuberosity, 24 at greater trochanter (without hip joint exposure) and 12 at femoral greater trochanter with exposure of the hip joint. Flaps were used to repair the pressure sores. ①Seventy-one sacrococcygeal pressure sores were repaired by the gluteal epithelial neurovascular flap; ②10 (10 patients) sacrococcygeal and 42 (36 patients) sciatic tubercle pressure sores were repaired by the posterior femoral neurovascular flap; ③24(24 patients) femoral trochanter pressure sores and 1(1 patient) sacrococcygeal pressure sore were repaired by the tensor fascia lata myocutaneous flap; ④2 (2 patients) sciatic tubercle pressure sores were repaired by the gracilis myocutaneous flap; ⑤12 (10 patients) femoral trochanter pressure sores were with hip joint exposure treated with hip joint amputation; ⑥8 (8 patients) pressure sores at ischial tuberosity were treated with VSD. The pressure sores were measured at 5.0 cm×8.0 cm-15.0 cm×30.0 cm, and the flaps were sized 10.0 cm×12.0 cm-17.0 cm×32.0 cm. The follow-up was conducted in 2 methods: visit of outpatient clinic by patients and WeChat distanced interview by medical staff.Results:The gluteal epithelial neurovascular flaps, tensor fasciae lata flaps, gracilis myocutaneous flaps and posterior femoral neurovascular flaps all survived; 4 of 10 posterior femoral neurovascular flaps had partial necrosis and healed after dressing change. A total of 139 patients were treated by flap repair, of which 136 pressure sores healed, except 1 sacrococcygeal pressure sore and 1 femoral greater trochanter pressure sore did not heal because the patient was in old age, long-term hypoproteinaemia and anaemia, and 1 ischial tubercle pressure sore failed to heal due to osteomyelitis osteomyelitis. Ten pressure sores at femoral greater trochanter decubitus with hip joint exposure treated by hip joint amputation and 8 pressure sores at ischial tubercle decubitus treated by simple insertion of VSD were all healed. The follow-up period was 0.5-15.0 years, 7.5 years in average. The results of follow-up showed that pressure sores healed without recurrence in 154 patients, but failed to heal in 3 patients.Conclusion:The gluteal epithelial neurotrophic vascular flap has reliable blood supply and is simple to harvest, and it is a good flap to repair sacrococcygeal pressure sores. The tensor fascia lata myocutaneous flap has reliable blood supply and is simple to harvest, hence it is a good flap to repair greater trochanteric pressure sores. Transposition of the posterior femoral cutaneous nerve nutrient vessel flap or the V-Y advancement flap is simple and effective in repair of the sciatic tuberosity pressure sores. However, it is not recommended to apply the transposition of posterior femoral cutaneous nerve nutrient vessel flap in repair of the sacrococcygobtaineal pressure sore, because it would cause a necrosis at the distal part of the flap. When a greater trochanteric pressure sore coexists with an expose of hip joint, the hip joint can be dissected. For the pressure sore at ischial tuberosity, and if there is a small wound with a large internal cavity, it can be treated with simple insertion of VSD.

Objective:To compare the clinical effects of 4 kinds of neurocutaneous perforator flap with vascular anastomosis for repair of hand and foot wounds.Methods:From January, 2005 to September, 2019, 112 patients with hand and foot wounds were treated, there were 78 cases of fingers, 11 cases of first web, 5 cases of palm, 6 cases of hand and 12 cases of foot. The defect area was 2.0 cm×1.5 cm-21.0 cm×12.0 cm. All 112 cases were repaired by neurocutaneous perforator flaps anastomosed with blood vessels. Types of flap were applied: Radial collateral artery perforator flap (with posterior cutaneous nerve of forearm) in 30 cases. The flap area was 5.0 cm×2.0 cm-13.0 cm×6.0 cm. Superficial peroneal artery flap (without superficial peroneal nerve) anastomosed with blood vessels in 15 cases. The flap area was 2.5 cm×2.0 cm-9.0 cm×6.0 cm. Lateral superficial sural artery perforator flap (with superior sural cutaneous nerve) in 26 cases. The flap area was 2.5 cm×1.8 cm-7.0 cm×5.0 cm. Peroneal artery perforator flap (with middle and lower sural nerve) in 41 cases. The flap was harvested with area of 2.5 cm×1.8 cm-23.0 cm ×14.0 cm to repair the wounds of feet, back of hands, first web, palm and fingers. CTA images were observed in 40 clinical patients, and the occurrence rate of radial collateral artery, superficial peroneal artery, superficial lateral sural artery, and peroneal artery were measured. Anastomosis cutaneous nerve in 97 cases, and no cutaneous nerve anastomosis 15 cases (superficial peroneal artery flap).Results:The peroneal artery perforator flap (41 cases) and radial collateral artery perforator flap (30 cases) were harvested. The incidence of perforator vessels was both 100%, and incidence of superficial sural artery was 80.8% (21/26 cases). In the other 19.2% (5/26 cases), the superficial medial sural artery was replaced by too thin vessels. The utilization rate of superficial peroneal artery was 60.0% (9/15 cases), the other 40.0% (6/15 cases) were converted to peroneal artery perforator flap. All flaps survived except 1 case of superficial perforator flap of lateral sural artery, which underwent necrosis at the distal end and healed after dressing change. One hundred and one cases were followed-up, including 90 cases for repairing soft tissue defects in hands and 11 cases in feet. The followed-up time ranged from 12 to 120 months, with an average of 36.6 months. There were 40 cases with excellent function, 45 cases with good function and 5 cases with fair function. There were 78 cases of cutaneous nerve anastomosis of hand flap, and the sensory function was above S 3 level. There were 12 cases without anastomosis of cutaneous nerve of hand flap, and the sensory function reached S 3 level in 3 cases and S 2 level in 9 cases. In 11 cases, the cutaneous nerve was anastomosed to repair the soft tissue defect of the foot, and the sensory function was above S 3 level. The radial collateral artery perforator flaps were relatively bulky and needed to be treated by fat removal. The other 3 kinds of three flaps were not bulky. Conclusion:The perforating vessels of peroneal artery and radial accessory artery have larger diameter and easy to harvest. The superficial peroneal artery and the lateral superficial sural artery are relatively small in caliber, especially the superficial peroneal artery. Among the 4 kinds of cutaneous nerve nutrient vascular flaps, the radial accessory artery perforator flap was the most bloated. Sensory nerve innervation flaps were found in the upper segment of lateral sural cutaneous nerve, posterior forearm cutaneous nerve and middle and lower segment of sural nerve. The superficial peroneal artery perforator flap was accompanied by superficial peroneal nerve that did not send cutaneous branches into the flap. The upper segment of superficial peroneal nerve was only a passing nerve.

Objective: To investigate the positive rate for 2019-nCoV tests and co-infections in Wuhan district. Methods: A total of 8 274 cases in Wuhan were enrolled in this cross-sectional study during January 20 to February 9, 2020, and were tested for 2019-nCoV using fluorescence quantitative PCR. Both respiratory tract samples (nasopharynx, oropharynx, sputum and alveolar lavage fluid) and non-respiratory tract samples (urine, feces, anal swabs, blood and conjunctival sac swabs) were collected. If both orf1ab and N genes are positive, they are classified as nucleic acid test positive group; if both orf1ab and N genes are negative, they are classified as negative group; if single gene target is positive, they are classified as suspicious group. Individuals were divided into male group and female group according to sex. At the same time, 316 patients were tested for 13 respiratory pathogens by multiplex PCR. Results: Among the 8 274 subjects, 2 745 (33.2%) were 2019-nCoV infected; 5 277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test; and 252 cases (3.05%) was not definitive (inconclusive result). The age of cases with COVID-19 patients and inconclusive cases was significantly higher than that of cases without 2019-nCoV infection (40 vs 56, t=27.569, P<0.001; 52 vs 56, t=6.774, P<0.001). The positive rate of 13 respiratory pathogens multiple tests was significantly lower in 104 subjects who were positive for 2019-nCoV compared with those in subjects who were negative for 2019-nCoV test (5.77% vs 18.39%, χ²=24.105, P=0.003). Four types of respiratory tract samples and five types of non-respiratory tract samples were found to be positive for 2019-nCoV nucleic acid test. Conclusion The 2019-nCoV nucleic acid positive rate in male is higher than in female. Co-infections should be pay close attention in COVID-19 patients. 2019-nCoV nucleic acid can be detected in non-respiratory tract samples.