Non-clinical reproductive toxicity studies typically employ mammals like rats, rabbits, and cynomolgus monkeys, with animal pregnancy being a key challenge in such testing. This article focuses on the difficulties encountered in the animal pregnancy process and potential countermeasures. Rats can be used for fertility and early embryonic development toxicity studies (Segment Ⅰ), embryo-fetal development toxicity studies (Segment Ⅱ), and perinatal toxicity studies (Segment Ⅲ). The estrous cycle of female rats can be determined by vaginal smear, and mating behavior is confirmed through copulatory plug checks the following day after pairing one female with one male in the same cage. Rabbits are commonly used in embryo-fetal development toxicity studies (Segment Ⅱ). Mating behavior between male rabbits and estrous females is observed to determine the time of conception. However, challenges such as atypical estrus of female rabbits, large variations in estrus between batches, and mating failure often occur in reproductive toxicity testing, which may be addressed through prolonged light exposure, increased protein supplementation, optimized mating strategies, and environmental modifications like female and male rabbits are raised adjacent to each other. Non-human primates (NHPs) are typically employed in perinatal toxicity studies (Segment Ⅲ), where one of the key challenges lies in accurately determining sexual maturity in males - a critical factor for reproductive toxicity testing, which can be assessed through comprehensive evaluation of age, body weight, and testicular volume. Generally, male macaques are considered sexually mature when they meet the following criteria: age >4.5 years, body weight >4.5 kg, single testis volume >10 mL, and combined testicular volume >20 mL. For pregnancy confirmation, ultrasound examination demonstrating visible gestational sacs is required, though this necessitates experienced veterinary clinicians to establish standardized ultrasound examination protocols. In conclusion, reproductive toxicity studies should employ species-appropriate detection methods and evaluation criteria based on anatomical characteristics of the reproductive system to ensure successful mating and proper study execution.

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 explore the diagnosis and treatment strategy of complex post-sternotomy mediastinitis with exposure of artificial implants (hereinafter referred to as implants).Methods:This study was a retrospective observational study. From January 2016 to January 2023, 16 patients with complex mediastinal infection with implant exposure after thoracotomy who met the inclusion criteria were admitted to Peking University First Hospital, including 9 males and 7 females, aged from 21 to 74 years. The infected wounds were subjected to multiple thorough debridement and negative-pressure wound therapy until the infection was controlled, and contrast-enhanced magnetic resonance imaging (MRI) examination was used to guide the operation after every debridement. During the operation, 5 cases of deep mediastinal pacing lead exposure, 1 case of deep mediastinal pacing lead exposure combined with pericardial patch exposure, 5 cases of pericardial patch exposure, 3 cases of artificial blood vessel exposure, and 2 cases of artificial blood vessel exposure combined with pericardial patch exposure were observed. Partial or complete implants were removed during debridement, therefore 8 patients who completely removed the middle mediastinum implants during the operation were included in the implant complete removal group. Then, according to the defects of the sternum and its surrounding soft tissue, unilateral or bilateral pectoralis major muscle flaps were used for chest wall reconstruction. The remaining 8 patients whose implants could not be completely removed were included in the implant partial removal group. The greater omentum flaps were used to cover the implants and fill the mediastinal defects. Two weeks later, the thigh medium-thickness skin grafts were transplanted on the surface of the greater omentum flaps. After debridement, the wound area was 20 cm×6 cm to 35 cm×10 cm. The area of pectoralis major muscle flap ranged from 15 cm×8 cm to 20 cm×10 cm, and the area of greater omentum flap ranged from 30 cm×15 cm to 40 cm×25 cm. The bacterial culture and high throughput sequencing test results of wound tissue samples of all patients were counted in the first debridement surgery. The hospitalization time, the time for C reactive protein (CRP) to decrease to normal level, and the number of operations were counted for all patients, and the above indexes of the two groups of patients were compared. During the follow-up, the wound recurrence of the patients was observed.Results:The positive ratio of bacterial culture in wound tissue samples was 14/16 in the first debridement surgery, and the positive ratio of high throughput sequencing test was 16/16, with staphylococcus aureus as the bacteria causing most infection among patients. Except for one patient who died during the treatment (a patient in implant partial removal group), the hospitalization time was (56±5) d, the time for CRP to decrease to normal level was (18.9±2.2) d, and the number of operations was (4.5±0.5) times in the remaining patients. Compared with those in implant partial removal group, the length of hospital stay and the time for CRP to decline to normal level of patients in implant complete removal group were significantly shorter (with t values of 3.12 and 3.12, respectively, P<0.05), and the number of operations of patients in implant complete removal group was significantly decreased ( t=3.38, P<0.05). All 15 surviving patients were followed up for more than 6 months, and no recurrence of mediastinitis was observed. Conclusions:The treatment of complex mediastinal infection with exposed implants after thoracotomy is difficult, especially the wounds when the implants cannot be completely removed during debridement. The application of contrast-enhanced MRI examination combined with transplantation of tissue flap such as greater omentum flap and pectoralis major muscle flap can achieve good repair effect.

Objective:To investigate the correlation between impulse oscillometry system examination indicators and conventional pulmonary ventilation function.Methods:The pulmonary ventilation function data of 10 883 patients from January 1, 2020 to December 31, 2022 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were included. The one-second rate [ratio of forced expiratory volume in the first second (FEV 1) to forced vital capacity (FVC)] measured as a percentage of the predicted value was ≥92% for the control group ( n=3 478) and <92% for the pulmonary obstruction group ( n=7 405). The obstruction group was subdivided into five groups according to the degree of pulmonary dysfunction: mild group ( n=3 938),moderate group ( n=1 142),oderate-severe group ( n=917),severe group ( n=737),and extremely severe group ( n=671). Conventional pulmonary ventilatory function FVC, FEV 1, one-second rate, and forced expired flow at 50% of FVC (MEF50%), forced expired flow at 75% FVC (MEF25%), maximal mid-expiratory flow (MMEF), peak expiratory flow (PEF), and pulsed oscillation pulmonary function test were detected in both groups of patients. Impedance at 5 Hz (Z5) means total respiratory resistance, resistance at 5 Hz (R5) means total airway resistance, reactance at 5 Hz (X5) indicates the elastic recoil of the peripheral airways, and resistance at 20 Hz (R20) represents resistance of the central airways. R5-R20 reflects resistance in the small airways. Additionally, peripheral resistance (Rp), respiratory resonance frequency (Frex), and area under the reactance curve (Ax) were also measured. Correlation between the indicators of the two groups and the sensitivity and specificity of the impulse oscillometry system parameters for the diagnosis of obstructive pulmonary ventilation dysfunction were analyzed. Results:Pulmonary function force expiratory volume in the first second as a percentage of predicted value (FEV 1%Pre) [80.10 (54.95,97.10)%],one-second rate [62.43(48.67, 67.02)%],MEF50% [1.33 (0.62,1.97)L/s],MEF25% [0.28 (0.17,0.41)L/s], MMEF [0.85 (0.43,1.29)L/s],and PEF [5.64 (3.73,7.50)]L/s in the obstruction group were significantly lower than those in the control group ( P<0.05). The differences within the subgroups of the obstruction group were also significant ( P<0.05). Pulsed oscillation Z5 [0.42 (0.33,0.55)kPa·L -1·s -1],Rp [0.25 (0.20,0.45)kPa·L -1·s -1], R5 [0.39 (0.31,0.49)kPa·L -1·s -1], R20 [0.28 (0.24,0.34)kPa·L -1·s -1], R5-R20 [0.09 (0.05,0.17)kPa·L -1·s -1],Frex [16.32 (13.07,20.84)Hz], and Ax [0.67 (0.28,1.64)] indices in the obstruction group were significantly higher than those in the control group. X5 [-0.14 (-0.23, -0.10)kPa·L -1·s -1] was significantly lower than that in the control group ( P<0.05). Z5, Rp, X5, R5, R5-R20, Frex, and Ax were statistically significant between different degrees of obstruction in the obstruction group ( P<0.05). The impulse oscillometry system parameters Z5, Rp, R5, R20, R5-20, Frex, and Ax were negatively correlated with the indices of conventional pulmonary ventilation ( r=-0.21-0.68, P<0.05), and the parameter X5 was positively correlated with the indices of conventional pulmonary ventilation ( r=0.41-0.68, P<0.05). The pulsed oscillation pulmonary function test parameters X5 (58.60%-95.68%) and Ax (57.08%-98.06%) presented the best sensitivity; X5 (86.29%-98.82%), Frex (86.69%-94.71%), and Ax (88.10%-98.53%) displayed the best specificity; and R20 presented the worst sensitivity and specificity. The sensitivity and specificity were slightly better in female patients than in male patients. Conclusion:The technical parameters of the impulse oscillometry system showed significant correlation with relevant indices of conventional pulmonary ventilation function detection. These well reflect the changes of different degrees of pulmonary ventilation function and have greater significance for reference in evaluating the degree of pulmonary function impairment.

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

Objective:To summarize the infective characteristics of Fournier's gangrene (FG) and evaluate the effect of negative pressure wound therapy (NPWT).Methods:A retrospective case control study was conducted to analyze the clinical data of 31 patients with FG admitted to Peking University First Hospital from May 2010 to September 2020, including 29 males and 2 females, aged 21-78 years [(55.2±2.0)years]. A total of 29 patients were caused by infectious diseases of the perianal and urinary system, and the rest two patients were caused by vulvar infection and retroperitoneal abscess. A total of 23 patients were treated with NPWT (Group A) and 8 patients were treated with conventional dressing (Group B). Characteristics of pathogen, drug-resistance rate, medical treatment and prognosis for all patients were summarized. The hospitalization duration, numbers of operation and wound healing time were compared between two groups.Results:Monomicrobial infection was identified in 14 patients, while polymicrobial infection in 15 patients, fungal infection in 1 and culture-negative in 1. Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae and Staphylococcus haemolyticus were the most common pathogenic bacteria. The resistance rate of gram-negative bacilli to third-generation cephalosporins was 37%. Staphylococcus haemolyticus were methicillin-resistant Staphylococcus. The carbapenem antibiotics combined with vancomycin antibiotics were used for all patients as the empirical anti-infection treatment. Three patients died, and the rest 28 patients were followed up for 3 to 12 months [(10.8±2.6)months] after discharge. All the wounds were healed well without recurrence. In Group A and Group B, the hospitalization duration was (37.4±15.0)days and (47.0±16.0)days, respectively ( P>0.05); the number of operation was 3(3, 6) times and 13(4, 17)times, respectively ( P<0.05); the wound healing time was (38.9±17.8)days and (61.8±14.2)days, respectively ( P<0.05). Conclusions:Enterobacteriaceae, Enterococcus and Staphylococcus haemolyticus are the most common pathogenic bacteria for FG, among which the proportion of drug-resistant bacteria is relatively high. NPWT is an effective adjuvant therapy for wound management with reduced operation times and short wound healing time compared to conrentional method.

Objective:To investigate the feasibility of negative-pressure wound therapy (NPWT) in the treatment of uncomplicated cardiac pacemaker pocket infection.Methods:From January 2013 to March 2020, 35 patients with uncomplicated cardiac pacemaker pocket infection were admitted to the Department of Cardiology of Peking University First Hospital, including 21 males and 14 females, aged 27 to 84 years. The retrospective cohort study was conducted. After a complete debridement followed by continuous NPWT (with negative pressure of -16.67 kPa), the pulse-generator was inserted into the new pocket between the musculus pectoralis major and pectoralis minor. Pressure drainage tube was put into the old pocket space. NPWT with the same mode was used again for 5 to 7 days after the wound was closed. The removed pocket tissue of patients was observed with hematoxylin-eosin staining. The wound healing on 10 to 12 days after the operation of pacemaker replacement was observed, and the recurrence of infection was observed during 6 to 42 months follow-up after operation.Results:The fibrous sac wall was observed in pocket tissue of the patients, and the tissue was partially covered with stratified epithelium, with many chronic inflammatory cells infiltration. Multinucleated giant cell reaction was observed in the tissue of some patients. Ten to twelve days after the operation of pacemaker replacement, 35 patients had good wound healing, and sutures were removed. After 6 to 42 months follow-up after operation, 31 patients were cured with no recurrence of infection and the wounds were well-healed; 4 patients who had recurrent infection received whole system of pacemaker removal after the operation.Conclusions:On the premise of complete debridement, NPWT is an alternative treatment for patients with uncomplicated cardiac pacemaker pocket infection.

Objective To explore a potentially effective treatment of postoperative deep infection after spinal instrumentation without removal of implants. Methods A total of 4 patients with postoperative deep infection after spinal instrumentation were treated at our hospital between January 2015 and May 2016. They were 2 men and 2 women, aged from 62 to 75 years (mean, 69.2 years). They were treated with ag-gressive surgical debridement under the guidance of methylene blue and negative pressure wound therapy. Reversed latissimus dorsi muscle flap was used to obturate the wound when the bacterial culture of the wound was negative and the relevant inflammatory indicators returned to normal. Negative pressure treatment con-tinued over the closed incision. Results The devices for negative pressure wound therapy were removed in the 4 patients one week after surgery. All the wounds were healed well by first intention 2 weeks after surgery without removal of their implants. The patients were discharged after their examinations for blood routine, CRP, ESR and PCT turned to be normal. Follow-ups for more than one year revealed no re-infection, implants loosening or other adverse effects. Conclusions Negative pressure wound therapy combined with reversed latissimus dorsi muscle flap is a new attempt to treat postoperative deep infection after spinal instru-mentation without implant removal. It may increase the rate of implants reserved, accelerate wound healing and raise the curative rate of deep infection.

Objective: Reconstruction of defects after wide resection of tumor in perineal region is challenging because the defects are extensive and complex. In this report, we retrospectively analyzed the clinical experience of perineal reconstruction in last 6 years, to evaluate the value of clinical application of perforator flaps in defects of perineal region. Methods: From January 2011 to December 2016, 32 cases of perineal cancer were treated by radical extensive excision, with defects repaired with perforator flaps. The size of perineal defects was between 8 cm×4 cm-20 cm× 20 cm, 52 perforator flaps were used for perineum reconstruction. Results: All of the defects achieved tension-free closure. All the flaps were survived and healed with first intention except two infection and minor wound dehiscence cases. Both cases healing after dressing and secondary suture. There were no donor-site complications. During an average follow-up of 11.1 months (range, 10-12 months), the reconstructed areas achieved good functional and cosmetic outcomes. Conclusions Perineum reconstruction with perforator flaps following total radical extensive excision leads to good result in patients with perineal cancer. It can achieve tension-free closure and produces almost normal appearance and function of the perineum.