ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

OBJECTIVE To investigate the ameliorative effect of ursolic acid on skin inflammation in rats with allergic contact dermatitis （ACD）， and explore its mechanism of action based on the Notch1/hairy and enhancer of split 1 （Hes1） signaling pathway. METHODS The ACD model was established by skin application of 2， 4-dinitrochlorobenzene. Forty successfully modeled rats were randomly divided into model control group （MC group）， ursolic acid low-dose group （UA-L group， 50 mg/kg）， ursolic acid high-dose group （UA-H group， 100 mg/kg）， and ursolic acid high-dose+Notch1 activator group （UA-H+Jagged1 group， 100 mg/kg ursolic acid+50 ng/kg Jagged1）， with 10 rats in each group. Another 10 rats with only hair shedding were selected as the normal control group. Rats in the administration groups were given the corresponding dose of ursolic acid intragastrically or/and Jagged1 by intraperitoneal injection once a day for 14 consecutive days. Twenty-four hours after the last treatment， the skin inflammation status and dermatitis scores of rats in each group were detected. The levels of interleukin-6 （IL-6）， IL-17 and IL-10 in serum and skin tissue were detected by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the pathological morphology of the skin tissue. Immunohistochemical staining and immunoblotting assay were used to detect the protein expressions of Notch1 and Hes1 in skin tissues. RESULTS Compared with the MC group， both the UA-L group and UA-H group exhibited significantly lower dermatitis scores， along with varying degrees of reduction in histopathological skin damage such as inflammatory cell infiltration. Additionally， the levels of IL-6 and IL-17 in serum and skin tissues were markedly decreased， while the levels of IL-10 were significantly increased in both groups； protein expressions of Notch1 and Hes1 were decreased significantly （P＜0.05）， and the improvements in the aforementioned indicators were more significant in the UA-H group （P＜0.05）. Jagged1 could significantly weaken the improvement effects of UA-H on the above indicators （P＜0.05）. CONCLUSIONS Ursolic acid may attenuate the expression of pro-inflammatory cytokines and enhance the expression of anti-inflammatory factors by blocking Notch1/Hes1 signaling pathway， thereby improving dermatitis symptoms in ACD rats.

OBJECTIVE: To investigate the effectiveness of using 3 hollow compression screws combined with 1 screw off-axis fixation under the guidance of three-dimensional (3D) printed guide plate with mortise-tenon joint structure (mortise-tenon joint plate) for the treatment of Pauwels type Ⅲ femoral neck fractures. METHODS: A clinical data of 78 patients with Pauwels type Ⅲ femoral neck fractures, who were admitted between August 2022 and August 2023 and met the selection criteria, was retrospectively analyzed. The operations were assisted with mortise-tenon joint plates in 26 cases (mortise-tenon joint plate group) and traditional guide plates in 28 cases (traditional plate group), and without guide plates in 24 cases (control group). There was no significant difference in the baseline data of gender, age, body mass index, cause of injury, and fracture side between groups ( P>0.05). The operation time, intraoperative blood loss, frequency of intraoperative fluoroscopy, incision length, incidence of postoperative deep vein thrombosis of lower extremity, pain visual analogue scale (VAS) score at 1 week after operation, and Harris score of hip joint at 3 months after operation were recorded and compared. X-ray re-examination was taken to check the quality of fracture reduction, fracture healing, and the shortening length of the femoral neck at 3 months after operation, and the incidences of internal fixation failure and osteonecrosis of the femoral head during operation. RESULTS: Compared with the control group, the operation time, intraoperative blood loss, and frequency of intraoperative fluoroscopy reduced in the two plate groups, and the quality of fracture reduction was better, but the incision was longer, and the differences were significant ( P<0.05). The operation time and intraoperative blood loss were significantly higher in the traditional plate group than in the mortise-tenon joint plate group ( P<0.05), the incision was significantly longer ( P<0.05); and the difference in fracture reduction quality and the frequency of intraoperative fluoroscopy was not significant between two plate groups ( P>0.05). There was 1 case of deep vein thrombosis of lower extremity in the traditional plate group and 1 case in the control group, while there was no thrombosis in the mortise-tenon joint plate group. There was no significant difference in the incidence between groups ( P>0.05). All patients were followed up 12-15 months (mean, 13 months). There was no significant difference in VAS score at 1 week and Harris score at 3 months between groups ( P>0.05). Compared with the control group, the fracture healing time and the length of femoral neck shortening at 3 months after operation were significantly shorter in the two plate groups ( P<0.05). There was no significant difference between the two plate groups ( P>0.05). There was no significant difference in the incidences of non-union fractures, osteonecrosis of the femoral head, or internal fixation failure between groups ( P>0.05). CONCLUSION For Pauwels type Ⅲ femoral neck fractures, the use of 3D printed guide plate assisted reduction and fixation can shorten the fracture healing time, reduce the incidence of postoperative complications, and be more conducive to the early functional exercise of the affected limb. Compared with the traditional guide plate, the mortise-tenon joint plate can reduce the intraoperative bleeding and shorten the operation time.
Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Bone Screws ; Adult ; Aged ; Treatment Outcome ; Printing, Three-Dimensional ; Operative Time

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases. Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion (DRG) neurons but does not occur in their central axonal branches. By performing rat sciatic nerve or dorsal root axotomy, we determined the expression of the dysbindin domain containing 2 (DBNDD2) in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury, respectively, and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury. Furthermore, we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development. Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury. Bioinformatic analysis data showed that transcription factor estrogen receptor 1 (ESR1) interacts with DBNDD2, exhibits a similar expression trend as DBNDD2 after axon injury, and may targets DBDNN2. These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
Animals ; Ganglia, Spinal/metabolism* ; Nerve Regeneration/genetics* ; Rats ; Axons/metabolism* ; Sciatic Nerve/injuries* ; Rats, Sprague-Dawley ; Male

Mechanical ventilation is commonly employed for respiratory support in patients with respiratory failure. Despite the optimization of ventilator parameters and treatment methods, mechanical ventilation can still lead to both acute and chronic lung injury in patients with acute respiratory distress syndrome (ARDS) as well as in those without ARDS, a phenomenon referred to as ventilator-induced lung injury (VILI). VILI can be categorized into four types: barotrauma, volumetric injury, atelectasis injury, and biotic injury. Among these, biotic injury, characterized by inflammation, plays a significant role in the pathogenesis of VILI. Numerous studies have investigated the inflammatory mechanisms underlying VILI; however, these mechanisms remain complex and not entirely understood. At present, clinical practice lacks specific prevention and treatment strategies for VILI, aside from the implementation of protective ventilation strategies. Long non-coding RNAs (lncRNA) are a category of non-coding RNA longer than 200 nucleotides. LncRNAs regulate physiological and pathological processes such as cell proliferation, apoptosis, inflammatory response, and immune regulation, this regulation occurs through mechanisms such as modulating gene activity, inhibiting specific states, assisting in transcription initiation, affecting pre-mRNA splicing modifications, influencing translation processes, and expressing biofunctional peptides. They play an important role in the course of multiple diseases. Studies have shown that compared with control animals and cell models, lncRNAs are differentially expressed in VILI animal models and cell stretch models. Experiments have verified that certain lncRNAs play a crucial role in the pathogenesis of VILI by regulating the expression of inflammatory factors, the transformation of macrophage types, neutrophil activation, and cell apoptosis. Given the adverse effects of VILI on mechanical ventilation in critically ill patients, the important role of lncRNAs in biological regulation, and the urgent need to explore more effective strategies for the prevention and treatment of VILI, this paper summarizes the mechanisms through which lncRNA contributes to the VILI process, and discusses its possibility as a diagnostic and therapeutic target of VILI, in order to provide a reference for the clinical treatment of VILI.
RNA, Long Noncoding ; Ventilator-Induced Lung Injury ; Humans ; Respiration, Artificial/adverse effects* ; Animals ; Respiratory Distress Syndrome ; Apoptosis

Objective To investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. Methods Ten male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. Results Nec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). Conclusions Necroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

Objective To analyze the changes in left ventricular deformation function in patients with diffuse large B-cell lymphoma(DLBCL)treated with different doses of anthracycline chemotherapy using 3D speckle-tracking imaging(3D-STI).Methods 66 DLBCL patients receiving anthracycline chemotherapy were enrolled.Based on the cumulative dose of anthracycline received,the patients were divided into a high-dose group(＞360 mg/m2,n=39)and a low-dose group(≤360 mg/m2,n=27).Patients underwent transthoracic echocardiography before chemotherapy and within one week after completion of the entire chemotherapy cycle.Left ventricular global longitudinal strain(LVGLS),left ventricular global circumferential strain(LVGCS),and other indices were analyzed using 3D-STI to assess changes in left ventricular deformation indices after chemotherapy and between two groups.Results Compared to baseline,DLBCL patients showed significant reductions in LVGLS,LVGCS and left atrial global longitudinal strain(LAGLS)after treatment completion(P＜0.001).When comparing the high-dose group with the low-dose group,there was a significant increase in relative LVGCS change rate at the end of chemotherapy(21.12[6.52,35.37]vs 5.49[-14.73,27.01];P=0.03).However,there were no statistically significant differences in relative left ventricular ejection fraction(LVEF),LVGLS,LVGCS,LVEF change rate,or LVGLS change rate between the two groups.Conclusions 3D-STI can be a potential method to identify the sub-clinical deterioration of left ventricular systolic function in patients received anthracycline chemotherapy,the difference of change rate of LVGCS may predict the variation of sub-clinical deterioration of left ventricular function between patients received high and low doses of anthracycline chemotherapy.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.

Objective:To explore the correlation between structural chromosomal abnormality and clinical characteristics of a child featuring gonadal dysplasia.Methods:A 13-year-old child who was admitted to Lianyungang Maternal and Child Health Care Hospital on February 7, 2023 for primary amenorrhoea and occasional abdominal pain was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected. G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. "Pseudodual centromere isochromosome X" and "psu idic(X)" were used as keywords to search the CNKI, Wanfang and PubMed databases, and the search period was set as from January 1, 2002 to June 1, 2023. Relevant literature on the structural abnormality of X chromosome was searched and analyzed retrospectively.Results:The child has a height of 153 cm and weighed 45 kg. She has no obvious facial dysmorphism. Laboratory tests showed that she had higher FSH and luteinizing hormone, and lower E2. Ultrasonography showed that she had small ovaries and rudimentary uterus. She was found to have a karyotype of 46, X, psu idic(X)(q21.3)[40]/mos 45, X[3], whilst both of her parents had a normal karyotype. CNV-seq showed that she had a 63.27 Mb deletion in Xq21.32q28 and a 91.59 Mb duplication in Xp22.33q21.32 (mosaicism rate = 74%). A total of 11 relevant literature were retrieved. Clinical phenotypes of patients with similar structural chromosomal abnormalities were diverse, which was closely related to the mosaicism rate of the 45, X karyotype and the location of the breaking point.Conclusion:46, X, psu idic(X)(q21.3)/45, X probably underlay the dysplasia of uterus and ovary and sex hormone abnormalities in this child, while her height was spared. Deletion of Xq21.32q28 is a key factor leading to Turner syndrome-like phenotype such as rudimentary uterus and ovarian dysplasia.