PANoptosis, a newly defined form of cell death, is characterized by the simultaneous occurrence and crosstalk of apoptosis, pyroptosis, and necroptosis. It has emerged as a promising therapeutic target for various diseases. Ovarian dysfunction is marked by oligomenorrhea or amenorrhea, elevated gonadotropin levels, and diminished estrogen levels, often accompanying subfertility or infertility. Additionally, it can manifest with perimenopausal syndrome and increase the risks of osteoporosis, cardiovascular disease, and cognitive impairments, seriously impacting patients' quality of life. While current studies have reported that ovarian hypofunction is associated with apoptosis, pyroptosis, or necroptosis, a systematic investigation into the relationship between PANoptosis and ovarian hypofunction is still absent. This review aims to elucidate the potential link between these two phenomena, providing new insights into the mechanisms underlying ovarian hypofunction and potential treatment strategies.
Humans ; Female ; Ovary/metabolism* ; Apoptosis ; Animals ; Necroptosis ; Ovarian Diseases/physiopathology*

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Objective:To analyze the reoperation rate and causes during the early adoption phase of unilateral biportal endoscopy (UBE).Methods:The clinical data of 180 patients who underwent UBE performed by a single surgeon at Beijing Friendship Hospital, Capital Medical University from October 2021 to June 2023 were retrospectively analyzed. Clinical and imaging data of patients who underwent reoperation were collected to analyze the causes of reoperation, and the clinical efficacy of the reoperations was also followed up. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used before and after treatment. Results:A total of 180 patients who underwent UBE were included in this study, of which 6 patients underwent reoperation, and the reoperation rate was 3.33%. Among them, 3 cases occurred in the first 90 surgeries and the other 3 occurred in the subsequent 90 surgeries. The causes of reoperation were as follows: recurrent lumbar disc herniation at the same segment postoperatively in 2 cases, insufficient decompression in 2 cases, disc herniation following isolated decompression in 1 case, and immediate postoperative perianal numbness in 1 case. The time between the initial surgery and reoperation ranged from 0 to 187 days, with an average of 63.3 days. The average follow-up time after reoperation was 18.3 months. The visual analogue scale (VAS) and Oswestry disability index (ODI) scores of the patients at the last follow-up were significantly improved compared with those before operation (VAS score of low back pain: 5.2 ± 1.7 before operation, 1.2 ± 0.8 at the last follow-up, P<0.001; VAS score of leg pain: 7.2 ± 1.5 before operation, 1.2 ± 1.2 at the last follow-up, P<0.001; ODI score: 67.3 ± 5.7 before operation, 20.2 ± 8.2 at the last follow-up, P<0.001). The postoperative modified MacNab scores were generally satisfactory (4 cases were rated as excellent, accounting for 66.7%; 2 cases were rated as good, accounting for 33.3%). Except for one patient who experienced dural injury during open revision surgery, there were no serious complications such as nerve damage. Conclusions:In the early stages of UBE surgery, recurrent lumbar disc herniation and inadequate decompression are the primary reasons for reoperation, typically occurring within the first three months postoperatively. Reoperation does not significantly increase the risk of nerve injury. Enhanced early postoperative follow-up is recommended. For symptomatic patients, a second surgery with thorough decompression can yield satisfactory treatment outcomes.

One of the earliest hallmarks of intervertebral disc degeneration is the decrease in nucleus pulposus (NP) water content, which is fundamentally driven by the loss and structural alteration of extracellular matrix (ECM) aggrecan. At its core, the true determinant of NP degeneration lies in the imbalance between cells and the ECM. During the transition from notochordal cells to mature NP cells, reductions in cell density and matrix synthesis capacity lead to an inherently diminished ability to produce and renew aggrecan. Subsequently, inflammation, acidification, abnormal mechanical loading, and hypotonic microenvironments further disturb aggrecan’s structure, expression, and aggregation state through cellular mechanosensing and transcriptional regulation. These processes decrease the fixed charge density and osmotic pressure of the NP, thereby weakening its hydration, load-bearing, and resilience capacities. This review focuses on the NP microenvironment, using aggrecan as the central molecular anchor, to summarize recent advances in NP research. By integrating insights from microstructural alterations, imaging changes, and therapeutic strategies, this work aims to provide a comprehensive reference for understanding and managing the progression of NP degeneration.

Objective:To investigate the expression characteristics of plasma proteins in patients with acute diquat poisoning by proteomic technology, and to screen the targets and biomarkers related to the diagnosis, treatment and prognosis of acute diquat poisoning.Methods:This study was a retrospective case-control study. Patients with diquat poisoning admitted to Nanjing University Affiliated Drum Tower Hospital from August 2022 to December 2023 were enrolled. Healthy volunteers matched for age and gender during the same period were selected as the control group. The general clinical data and plasma samples were collected, and qualitative and quantitative analyses of plasma proteins were performed by proteomic technology based on nanoliter liquid chromatography tandem quadrupole time-of-flight mass spectrometry. Mann-Whitney U test was used to compare differences of plasma protein expression between the two groups. Results:A total of 8 diquat poisoning patients and 7 healthy individuals were included in this study, and 491 plasma proteins were identified. Compared with control group, 76 differentially expressed proteins were obtained from the poisoned group, including 35 up-regulated proteins and 41 down-regulated proteins. GO analysis showed that the differentially expressed proteins were mainly associated with oxygen transporter activity, receptor binding, and hyaluronic acid-binding endopeptidase inhibitor activity. KEGG pathway enrichment analysis revealed that differentially expressed proteins were associated with complement and coagulation cascades, neutrophil extracellular trap formation, and platelet activation. In addition, the expression of adiponectin (ADIPOQ) was not only increased in poisoned patients, but also significantly higher in non-survivors than in survivors ( P<0.01). Conclusions:Multiple plasma proteins with abnormal expression may be involved in the pathological process of acute diquat poisoning. ADIPOQ may have potential application value in the diagnosis, treatment, and prognosis of acute diquat poisoning.

Objective: To construct and to validate a nomogram prediction model based on Lipoprotein-associated phospholipase A2(Lp-PLA2) and Lipoprotein(a) [LP(a) ]for predicting the risk of major adverse cardiovascular events(MACE) in patients with coronary heart disease(CHD). Methods: A retrospective analysis was conducted on the clinical data of 442 patients with coronary heart disease(CHD). Among them,411 patients who completed follow-up were randomly divided into a training set(288 cases) and a validation set(123 cases) at a 7 ∶ 3 ratio.Independent risk factors for major adverse cardiovascular events(MACE) in CHD patients were screened through Lasso regression analysis and Cox regression analysis,and a nomogram prediction model was constructed. The predictive performance of the model was evaluated using time-dependent receiver operating characteristic curves(ROC),calibration curves,and decision curve analysis. Results: Variables were screened through Lasso regression and Cox regression analysis. The final model included nine independent predictors,namely age,smoking history,clinical phenotype of CHD,the number of coronary artery lesions,Gensini score,BNP,Lp-PLA2,LP(a), and the history of statin use. The area under the ROC curve in the training set was 0. 897,0. 885,and 0. 909 at 1,2,and 3 years,respectively; The area under the ROC curve in the validation set was 0. 885,0. 881,and 0. 923 at 1,2,and 3 years,respectively. These results demonstrated that the model had excellent discriminatory power. The calibration curves and decision curves demonstrated that the model had high clinical practicality in predicting the occurrence of MACE in CHD patients. Conclusion The nomogram prediction model based on LP-PLA2,LP(a)and other risk factors provides an effective tool for the prognosis assessment of CHD patients,facilitating the early identification of high-risk patients and enabling individualized intervention.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Background and purpose:Tumor-associated macrophages(TAM)as the main stromal cells in the tumor microenvironment play an important role in tumor progression.This study aimed to explore the clinical significance of M1 type TAM infiltration in hepatocellular carcinoma(HCC).Methods:We collected tissue paraffin samples from 320 HCC patients who underwent surgery at the Affiliated Nantong Hospital Three of Nantong University from January 2012 to December 2020.Immunohistochemical methods were used to detect the distribution of CD86 labeled M1 type TAM in HCC tissues,and positive cell density was calculated.Groups were established according to cell density,high-density group had cells with greater than average density(29 cells/mm2),and low-density group had cells with less than or equal to average density.The correlation and prognostic significance of M1 TAM density with clinicopathologic features and tumor infiltrating CD8+T lymphocytes of HCC were analyzed.Using immunohistochemistry to detect the expression of programmed death ligand-1(PD-L1),the cases were divided into four groups based on the cell density of CD86 and PD-L1.In the CD86+high-density group,PD-L1 high-density(CD86highPD-L1high)and PD-L1 low-density(CD86highPD-L1low)groups were included.In the CD86+low-density group,the PD-L1 high-density(CD86lowPD-L1high)and PD-L1 low-density(CD86lowPD-L1low)groups were included.We analyzed the prognostic significance of CD86+M1 type TAM density combined with PD-L1 expression.This study was approved by the Ethics Committee of Affiliated Nantong Hospital Three of Nantong University(ethics number:EK2022005).Results:CD86+M1 type TAM was mainly distributed in the tumor stroma.Its high-density rate was 44.7%(143/320).The density of CD86+M1 type TAM was positively correlated with tumor infiltrating CD8+T lymphocyte density(P＜0.001)and negatively correlated with hepatitis B virus surface antigen(HBsAg)positivity(P=0.003),and had no significant correlation with clinical and pathological features such as patient age,gender,cirrhosis,tumor size,histological grading and microvascular invasion.The CD86+M1 type TAM high-density group had better overall survival(OS)and disease-free survival(DFS)than the low-density group,and the differences were statistically significant(all P＜0.001).Multivariate Cox proportional hazards regression model analysis showed that low-density CD86+M1 type TAM was an independent risk factor for evaluating OS and DFS(OS:HR=1.468,P=0.022;DFS:HR=2.233,P＜0.001).The CD86highPD-L1high group had poor OS and DFS than the CD86highPD-L1low group,and the differences were statistically significant(both P＜0.05).The CD86lowPD-L1high group had poor OS and DFS than the CD86lowPD-L1low group.The difference in OS between the two groups was statistically significant(P＜0.05),while the difference in DFS was not statistically significant.Conclusion:The presence of high-density CD86+M1 type TAM in HCC tissue suggests a good prognosis and is an independent prognostic factor.Expression of PD-L1 in HCC tissue suggests increased invasiveness and poorer prognosis.

Objective To investigate the safety and prognostic analysis of surgical resection after conversion therapy and downgrad-ing of initial unresectable advanced hepatocellular carcinoma.Methods Clinical data was retrospectivly collected from 53 unresectable advanced hepatocellular carcinoma patients who received combined treatment with tyrosine kinase inhibitor(TKI)and programmed death-1(PD-1)inhibitors in the Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2021.Tumor re-sponse and resectability were evaluated through modified response evaluation criteria in solid tumors(mRECIST).Emphasis was placed on analyzing the clinical characteristics,effects of conversion therapy,adverse drug reactions,surgical outcomes,postoperative complica-tions and survival of patients undergoing surgical resection,in order to evaluate surgical safety and prognosis.Results Among 53 patients with initially unresectable advanced liver cancer,12 patients(22.6％)underwent R0 resection surgery within 101(92,153)days after the start of combination therapy.At the initial examination,the median maximum tumor diameter of these 12 patients was 8.2(4.7,10.3)cm,and 6 patients of them were in CNLC Ⅲ a stage;4 patients were in CNLC Ⅲ b stage,including 3 patients of retroperitoneal lymph node metastasis and 1 patient of left adrenal metastasis.Preoperative evaluation:2 patients showed complete remission,9 patients showed partial remission,and 1 patient showed stable disease.There were 3 patients of postoperative complications of grade Ⅱ or above.The cumulative postoperative survival rates at 6months,1 year,and 2 years were 100.0％,91.7％,and 66.7％,respectively.The re-currence-free survival rates at 6months,1 year,and 2 years were 91.7％,66.7％,and 50.0％,respectively.Conclusion After full preoperative evaluation,surgical resection is safe and effective for the initial unresectable advanced liver cancer after conversion therapy and downgrading.

Objective To investigate the safety and prognostic analysis of surgical resection after conversion therapy and downgrad-ing of initial unresectable advanced hepatocellular carcinoma.Methods Clinical data was retrospectivly collected from 53 unresectable advanced hepatocellular carcinoma patients who received combined treatment with tyrosine kinase inhibitor(TKI)and programmed death-1(PD-1)inhibitors in the Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2021.Tumor re-sponse and resectability were evaluated through modified response evaluation criteria in solid tumors(mRECIST).Emphasis was placed on analyzing the clinical characteristics,effects of conversion therapy,adverse drug reactions,surgical outcomes,postoperative complica-tions and survival of patients undergoing surgical resection,in order to evaluate surgical safety and prognosis.Results Among 53 patients with initially unresectable advanced liver cancer,12 patients(22.6％)underwent R0 resection surgery within 101(92,153)days after the start of combination therapy.At the initial examination,the median maximum tumor diameter of these 12 patients was 8.2(4.7,10.3)cm,and 6 patients of them were in CNLC Ⅲ a stage;4 patients were in CNLC Ⅲ b stage,including 3 patients of retroperitoneal lymph node metastasis and 1 patient of left adrenal metastasis.Preoperative evaluation:2 patients showed complete remission,9 patients showed partial remission,and 1 patient showed stable disease.There were 3 patients of postoperative complications of grade Ⅱ or above.The cumulative postoperative survival rates at 6months,1 year,and 2 years were 100.0％,91.7％,and 66.7％,respectively.The re-currence-free survival rates at 6months,1 year,and 2 years were 91.7％,66.7％,and 50.0％,respectively.Conclusion After full preoperative evaluation,surgical resection is safe and effective for the initial unresectable advanced liver cancer after conversion therapy and downgrading.