Objective: To investigate the effect of integrin α5 on the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in periodontal ligament fibroblasts (PDLFs) within an inflammatory microenvironment. Methods: This study was approved by the Ethics Committee of Laboratory animals. After rat PDLFs were treated with LPS (0.5, 5, and 50 µg/mL) for 24 h, the primary medium was discarded and replaced with serum-free culture medium. After 24 h, the supernatant was collected and mixed with DMEM medium containing 10% exosome-free serum at a volume ratio of 1:1 to obtain conditioned medium (CM). The groups were labeled as the 0.5-CM, 5-CM, and 50-CM groups. In addition, PDLFs cultured in DMEM medium containing 10% exosome-free serum were considered the 0-CM group. PDLFs were cultured with the above CM. In the inhibitor group, PDLFs were cultured in 0-CM containing different concentrations of integrin α5 inhibitor ATN-161 (0, 0.025, 0.25, 2.5, 25, and 250 μg/mL). The effect of CM and integrin α5 inhibitor ATN-161 on cell viability was assessed using the CCK-8 assay. According to the CCK-8 results, in further inhibitor intervention experiments, PDLFs were cultured in 0-CM, 5-CM (without/with 25 μg/mL ATN-161), and 0-CM containing 25 μg/mL ATN-161, which were labeled as the 0-CM, 5-CM, ATN-161+5-CM, and ATN-161 groups, respectively. The expression changes of integrin α5 and NLRP3 were detected using Western blot and qRT-PCR techniques. For in vivo experiments, 24 rats were randomly divided into four groups (n=6). The control group contained healthy rats that received no treatment. The rats in the other three groups were injected with 40 µL of 0-CM containing 25 μg/mL ATN-161 or 5-CM (without or with 25 μg/mL ATN-161) on the palatal side of the left maxillary first molar every three days; these groups were classified as the ATN-161, 5-CM, and ATN-161+5-CM groups, respectively. On the 30th day, the left maxillary tissue of rats was used for Micro-CT, HE staining, and immunohistochemical detection. Results : The CCK-8 assay showed that CM, 25 μg/mL ATN-161, and ATN-161 concentrations below 25 μg/mL had no significant effect on cell viability at 12 h and 24 h (P > 0.05). 50-CM and 25 μg/mL ATN-161 significantly inhibited cell viability at 48 h (P < 0.05). For in vitro experiments, compared to the 0-CM group, both the protein and mRNA levels of integrin α5 and NLRP3 were significantly increased in rat PDLFs in the 5-CM group (P < 0.05). Intervention with 25 μg/mL ATN-161 significantly attenuated the enhancement of 5-CM on the expression of integrin α5 and NLRP3 (P < 0.05). For in vivo experiments, compared to the control group, alveolar bone resorption and periodontal inflammatory cell infiltration were significantly increased in the 5-CM and ATN-161+5-CM groups, and the expression of integrin α5 and NLRP3 was significantly increased (P < 0.01). However, compared to the 5-CM group, the ATN-161+5-CM group had less alveolar bone resorption and fewer periodontal inflammatory cells. Further, the expression of integrin α5 and NLRP3 was significantly reduced (P < 0.01). Conclusion In vitro and in vivo experiments showed that integrin α5 mediated NLRP3 expression in PDLFs under an inflammatory microenvironment. ATN-161 inhibited the expression of integrin α5, thus significantly downregulating the expression of NLRP3, which plays a role in inhibiting inflammation.

Megakaryocytes and hepatocytes are unique cells in mammals that undergo polyploidization through endomitosis in terminal differentiation. Many polyploidization regulators and underlying mechanisms have been reported, most of which are tightly coupled with development, organogenesis, and cell differentiation. However, the nature of endomitosis, which involves successful entry into and exit from mitosis without complete cytokinesis, has not yet been fully elucidated. We highlight that endomitosis is a new cell fate in the cell cycle, and tetraploidy is a critical stage at the bifurcation of cell fate decision. This review summarizes the recent research progress in this area and provides novel insights into how cells manipulate mitosis toward endomitosis. Endomitotic cells can evade the tetraploidy restrictions and proceed to multiple rounds of the cell cycle. This knowledge not only deepens our understanding of endomitosis as a fundamental biological process but also offers new perspectives on the physiological and pathophysiological implications of polyploidization.
Hepatocytes/physiology* ; Megakaryocytes/physiology* ; Humans ; Polyploidy ; Animals ; Cell Cycle/physiology* ; Cell Differentiation ; Mitosis/physiology*

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective:To explore the strategies and technical points for breast reconstruction using free lower abdominal skin flap transplantation through lateral chest incision.Methods:The data of patients who underwent unilateral breast reconstruction with free lower abdominal flap transplantation using lateral thoracic incision in Hunan Cancer Hospital from October 2022 to March 2023 were retrospectively analyzed. Lateral thoracic incision was used in the recipient area. Firstly suitable radical mastectomy was performed for patients with early onset of breast cancer or recurrence after breast-conserving surgery, and prosthetic dilator removal or breast capsule release was performed for patients with dilator removed or capsular contracture after breast cancer prosthesis reconstruction. After that, the free lower abdominal skin flap breast reconstruction was completed under the same incision. During the operation, blood vessel preparation in the recipient area, skin flap preparation in the donor area, blood vessel anastomosis and breast shaping were completed successively according to the actual situation of the patient. Postoperative observation of complications, follow-up evaluation of reconstructed breast appearance and donor site healing were carred out.Results:A total of 15 female patients were included, aged range from 24 to 57 years old, with an average of 42.3 years old. There were 9 cases of early breast cancer, 2 cases of breast cancer recurrence after breast conserving surgery, 2 cases of breast cancer with dilator removed after breast reconstruction, and 2 cases of capsule contracture after breast cancer prosthesis reconstruction. The length of the lateral chest incision was 7.5-11.2 cm, with an average of 8.7 cm. Six cases were performed with 3/4 of the lower abdominal skin flaps, using a unilateral inferior abdominal vascular pedicle. The volume of the flaps ranged from 19.0 cm × 10.0 cm × 4.5 cm to 23.0 cm × 13.0 cm × 6.0 cm. The weight ranged from 280 to 510 g, with an average of 370 g. Nine cases were performed by cutting the entire lower abdominal skin flap and using bilateral inferior abdominal vascular pedicle. The volume of the skin flaps ranged from 27.0 cm × 11.0 cm × 5.0 cm to 30.0 cm × 14.0 cm × 6.5 cm. The weight ranged from 420 to 730 g, with an average of 530 g. Nine cases were selected as the main trunk of the thoracic and dorsal blood vessels, 4 cases were selected as the anterior serratus branch of the thoracic and dorsal blood vessels, and 2 cases were selected as the main trunk of the thoracic and dorsal blood vessels combined with the anterior serratus branch. One flap experienced venous crisis and the surgery failed, while the remaining 14 flaps survived smoothly. Follow-up period was 6-17 months, with an average of 10.4 months. The reconstructed breast had a satisfactory appearance and texture, without skin flap contraction or deformation. The skin flap donor area and breast recipient area only had linear scars, and there was no significant impact on abdominal wall and shoulder joint function. There was no tumor recurrence or metastasis during follow-up.Conclusion:When the side chest incision is used to perform the related operations of breast cancer radical resection, the free lower abdominal skin flap can be transplanted into the same incision for breast reconstruction. The effect is satisfactory, and the damage of the affected area is further reduced.

Objective:To explore the clinical value and therapeutic effects of endoscopic nipple-sparing mastectomy combined with immediate breast reconstruction using an oblique pedicled rectus abdominis myocutaneous flap(ORAMF).Methods:The data of patients admitted to Hunan Cancer Hospital from May to September 2023 who underwent breast cancer resection followed by immediate breast reconstruction with ORAMF were analyzed retrospectively. Surgical methods: firstly, axillary anterior sentinel lymph node biopsy and subcutaneous glandular excision for breast cancer were performed through a lateral chest incision using an endoscopic technique. Subsequently, a unilateral ORAMF was prepared by removing the epidermis and creating subcutaneous tunnels on the surface of the rectus abdominis myocutaneous flap under direct visualization. The subcutaneous tunnel of the flap was then extended to the deep surface of the breast with the assistance of an endoscope, allowing for the transfer of the ORAMF to reconstruct the breast. Post surgery, the flap survival was monitored, and after discharge, patients received enhanced anti-scar treatment and functional rehabilitation exercises. Follow-up assessments included the evaluation of the reconstructed breast shape, incision scarring in both the donor and recipient areas, abdominal wall function, tumor recurrence and metastasis.Results:A total of 8 female patients with unilateral breast cancer were included in this study, aged between 27 and 52 years, with a mean age of 41.7 years old. The body mass index of the patients ranged from 19.1 to 22.5 kg/m 2. All patients had early-stage breast cancer. During the operation the average mass of the resected breast was 245 g(ranging from 220 to 285 g). The length of the lateral thoracotomy incision varied from 6.9 to 9.5 cm, with a mean length of 7.7 cm. In 3 cases, the ipsilateral ORAMF was used for breast reconstruction, while in 5 cases, the contralateral ORAMF was utilized. The dimensions of the flap were as follows: length (20.4±0.7) cm, width (10.8±1.5) cm, thickness (5.4±0.9) cm, with the volume of the flap cutting ranging from 19.7 cm×9.2 cm×4.4 cm to 21.2 cm×11.8 cm×5.9 cm. All of the flaps exhibited good blood supply and survived successfully without the need for additional anastomotic vessels. The patients were followed up for a period of 8 to 10 months post-operation, with an average follow-up of 8.7 months. The reconstructed breasts maintained a good shape and texture, showing no contracture or deformation of the flap, and were generally symmetrical with the healthy breast. The incisions in both the flap donor area and the recipient area had healed well, leaving only linear scars, and the function of the abdominal wall was not significantly compromised. No recurrence or metastasis was observed during the follow-up period. Conclusion:The endoscopic technique helps to preserve the integrity of the breast skin tissue to the greatest extent possible, reducing scarring and assisting in the creation of subcutaneous tunnels to facilitate the transposition of the ORAMF for breast reconstruction. For carefully selected patients with moderately small breasts and ample subcutaneous tissue in the lower abdomen, the preparation of a unilateral ORAMF for breast reconstruction can yield superior results. This approach minimizes additional damage to the donor area, enhancing the safety of the surgery while significantly reducing the complexity of the operation.

The etiology and pathological morphology of atlantoaxial dislocation (AAD) are complex. Based on the pathological anatomical characteristics of AAD, combined with clinical techniques, it is essential to formulate reasonable classification criteria and develop corresponding treatment strategies for different types of AAD. The satisfactory outcome of surgical treatment for AAD can only be achieved through the comprehensive application of various atlantoaxial reduction techniques, tension band releasing techniques, internal fixation and fusion techniques. This article discusses the latest advancements in surgical treatment techniques for AAD, thoroughly explores treatment strategies based on different types of AAD, and analyzes the practicality and effectiveness of clinical classification and treatment strategies. The posterior atlantoaxial facet releasing and distraction compression reduction technique may pose challenges to traditional treatment strategies in the future. In the development of surgical treatment techniques for AAD, microspinal surgical techniques may play a significant role in improving surgical methods and enhancing treatment outcomes.

Craniovertebral junction malformation is a congenital malformation located in the foramen magnum and upper cervical spine, including bone and nerve malformation, resulting in motor and sensory disorders, cerebellar and lower cranial nerves, etc. The evaluation methods of clinical symptoms and efficacy of craniovertebral junction malformation are important for the surgical indications and effects, mainly including the evaluation of clinical symptoms and the quality of life. At present, the commonly used methods in clinical work and literature are the Japanese orthopaedic association scores, visual analogue scales, 36-item short-form health survey, etc. Most of these clinical evaluations are not aimed at craniovertebral junction diseases but focus on the description of a certain type of clinical symptoms. Chicago Chiari outcome scale and syringomyelia outcome scale of Xuanwu hospital are dedicated to Craniovertebral junction malformation, but more clinical studies are needed to prove their effectiveness. Based on the literature reports, this article reviewed the previous clinical evaluation methods of craniovertebral junction malformation and discusses their applications and limitations.