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*

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.

Background:The musk glands of adult male Chinese forest musk deer(Moschus berezovskii Flerov,1929)(FMD),which are considered as special skin glands,secrete a mixture of sebum,lipids,and proteins into the musk pod.Together,these components form musk,which plays an important role in attracting females during the breeding season.However,the relationship between the musk glands and skin of Chinese FMD remains undiscovered.Here,the musk gland and skin of Chinese FMD were examined using histological analysis and RNA sequencing(RNA-seq),and the expression of key regulatory genes was evaluated to determine whether the musk gland is derived from the skin.Methods:A comparative analysis of musk gland anatomy between juvenile and adult Chinese FMD was conducted.Then,based on the anatomical structure of the musk gland,skin tissues from the abdomen and back as well as musk gland tissues were obtained from three juvenile FMD.These tissues were used for RNA-seq,hematoxylin-eosin(HE)staining,immunohistochemistry(IHC),western blot(WB),and quantitative real-time polymerase chain reaction(qRT-PCR)experiments.Results:Anatomical analysis showed that only adult male FMD had a complete glandular organ and musk pod,while juvenile FMD did not have any well-developed musk pods.Transcriptomic data revealed that 88.24%of genes were co-expressed in the skin and musk gland tissues.Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis found that the genes co-expressed in the abdomen skin,back skin,and musk gland were enriched in biological development,endocrine system,lipid metabolism,and other pathways.Gene Ontology(GO)enrichment analysis indicated that the genes expressed in these tissues were enriched in biological processes such as multicellular development and cell division.Moreover,the Metascape predictive analysis tool demonstrated that genes expressed in musk glands were skin tissue-specific.qRT-PCR and WB revealed that sex-determining region Y-box protein 9(Sox9),Caveolin-1(Cav-1),and androgen receptor(AR)were expressed in all three tissues,although the expression levels differed among the tissues.According to the IHC results,Sox9 and AR were expressed in the nuclei of sebaceous gland,hair follicle,and musk gland cells,whereas Cav-1 was expressed in the cell membrane.Conclusions:The musk gland of Chinese FMD may be a derivative of skin tissue,and Sox9,Cav-1,and AR may play significant roles in musk gland development.

Objective: To identify the characteristics of social network and the association between ego-centric network and HIV status among young MSM Chinese students. Methods: The cross-sectional study was conducted in Chongqing, Tianjin, Harbin and Xi an city from April to December 2017 and from March to May 2018. A mixed recruitment method of snowball sampling and RDS approach was used to recruit participants who reported information on social network and received HIV test. The Multiple Regression Analysis method was used to for the analysis of association between ego-centric social network and HIV status of men who have sex with men (MSM) among young students. Results: The sample included 547 participants who nominated 1 088 social partners in total with average age of 13 to 60 years old. The MSM with different sexual orientation from their social members (aOR=0.38), embedded in a large network (aOR=0.63), with a high individual betweenness centrality (aOR=0.27) were at lower risk of HIV-positive status; while MSM who differed greatly in education level with their social members(aOR=1.60), existed in sexual networks(aOR=1.41), existed in the “risky networks” (aOR=1.88) , with high network density (aOR=1.91) and a high individual degree (aOR=4.10) had higher risk of HIV-positive status(P<0.05). Conclusion MSM with great difference in education level from social members, existed in sexual networks, with a large network density and a high degree were exposed to higher risk of HIV-positive status.

Objective: To understand the characteristics of sexual partners and the influence of having multiple sexual partners on substance use among young male students man who have sex with men (MSM) in China, and to provide scientific basis for the prevention and control of HIV/AIDS among young MSM students. Methods: A mixed recruitment method of snowball sampling and respondent driven sampling was used to recruit young MSM students in Beijing and Tianjin, and a questionnaire survey was conducted among 220 participants from November to December 2019. Chi-square test and generalized linear model multi-factor Logistic regression were used to analyze the influencing factors of substance use before sexual behavior. Results: The average age of them was (22.39±2.57) years old, 84.5% of them were students, the average age of first sexual behavior was (18.83±2.45) years old, 44.1% of them had two or more sexual partners (including fixed sexual partners, temporary sexual partners and commercial sexual partners), 22.7% had more than one male fixed partner. After adjusting for age and education, having multiple sexual partners was risk factor for drinking alcohol before sex (aOR=2.97) or substance abuse (aOR=2.39). Having male temporary sexual partner was an risk factor in substance use before sexual behavior(OR=4.10). Conclusion The characteristics of sexual partners among young MSM students are complex, and the proportion of multiple sexual partners is high. Having fixed single sexual partner can reduce the risk of substance use before sexual behavior. AIDS prevention education for young MSM students should be further strengthened.

Aiming at the lack of quantitative evaluation methods in clinical diagnosis of lung cancer, a classification and prediction model of lung cancer based on Support Vector Machine (SVM) was constructed by using radiomics method. Firstly, the definition and processing flow of radiomics were introduced. The experimental samples were selected from 816 lung cancer patients on LIDC. Firstly, ROI was extracted by central pooling convolution neural network segmentation method. Then, Pyradiomics and FSelector feature selection models were used to extract features and reduce dimension. Finally, SVM was used to construct the classification and prediction model of lung tumors. The predictive accuracy of the model is 80.4% for the classification of benign and malignant pulmonary nodules larger than 5 mm, and the value of the area under the curve (AUC) is 0.792. This indicates that the SVM classifier model can accurately distinguish benign and malignant pulmonary nodules larger than 5 mm.
Algorithms ; Humans ; Lung Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Radiometry ; Support Vector Machine ; Tomography, X-Ray Computed

OBJECTIVE： To investigate estrogen-like effect of tetrahydroxy stilbene glucoside （TSG） and its effects on the expression of estrogen receptor （ER） in uterus of sexually immature mice. METHODS： Totally 60 sexually immature Kunming mice were randomly divided into normal group， positive control group （estradiol valerate， 0.18 mg/kg）， TSG low-dose and high-dose groups （50， 150 mg/kg）， TSG low-dose and high-dose groups+estradiol valerate groups （same dose as medication alone group）. Normal group was given constant volume of water intragastrically， and administration groups were given relevant medicine 0.2    mL/10 g， once morning and night， for consecutive 5 d. The uterus index and body weight increase of mice in each group were determined and calculated the next day after the last administration. The contents of serum estrogen （E2， LH， FSH） were determined by ELISA. HE staining was used to observe the morphology characteristics of uterus， and uterine tube diameter and endometrial thickness were detected. The expression of ER（ER-α and ER-β） in uterus was detected by immunohistochemical staining. RESULTS： The myometrium of the mice in normal group was parallel and compact， the epithelium of the uterus was columnar， and the expression of ER-α and ER-β was low. The uterine tube diameter， endometrium and epithelium of mice in each administration group increased， thickened or proliferated in varying degrees， and the expression of ER-α and ER-β changed. Compared with normal group， uterus indexes （positive control group， TSG high-dose group， TSG+estradiol valerate groups）， the increase of body weight （positive control group， TSG high-dose groups， TSG low-dose+estradiol valerate group）， uterine tube diameter and endometrial thickness （positive control group， TSG low-dose group， TSG+estradiol valerate groups）， the expression of ER-α （positive control group， TSG+estradiol valerate groups） and the expression of ER-β （postive control group， TSG high-dose+estradiol valerate group）were increased significantly， while serum contents of LH （positive control group， TSG high-dose group） and FSH （TSG low-dose+estradiol valerate group） were decreased significantly （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression in ER-α and ER-β of TSG+estradiol valerate groups， the increase of body weight and serum content of E2 in TSG low-dose+estradiol valerate group were significantly higher than same TSG dose alone groups （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression of ER-α and ER-β in TSG groups， uterine tube diameter and the expression of ER-β in TSG+estradiol valerate groups， body weight increase of mice in TSG low-dose group were significantly lower than positive control group， while serum content of LH in TSG+estradiol valerate groups were significantly higher than positive control group （P＜0.05 or P＜0.01）. CONCLUSIONS： TSG can increase uterus indexes and body weight of sexually immature mice to certain extent， regulate estrogen level， increase the diameter of uterine tube and endometrial thickness and up-regulate the expression of ER in the uterus， showing certain estrogen-like effect， which is weaker than that of estradiol valerate. Combined use of them may antagonize the effect of estradiol valerate.

Objective To evaluate the effects of lipoxin A4 (LXA4) on human type Ⅱ alveolar epithelial cell wound repair,proliferation and apoptosis.Methods Experiment Ⅰ Human type Ⅱ alveolar epithelial cells were inoculated in 24-well plates and divided into 4 groups (n=10 each) using a random number table:control group (group C),1 nmol/L LXA4 group (group L1),10 nmol/L LXA4 group (group L2) and 100 nmol/L LXA4 group (group L3).Cells were cultured in normal culture atmosphere in group C.Cells were incubated with 1,10 and 100 nmol/L LXA4 in L1,L2 and L3 groups,respectively.The scratch wound assay was performed at 36 h of culture or incubation.Cell proliferation was measured at 24 h of culture or incubation.Experiment Ⅱ Human type Ⅱ alveolar epithelial cells were inoculated in 96-well plates and divided into 5 groups using a random number table:control group (group C,n=10),Fas-ligand group (n =10),Fas-ligand+LXA4 group (n =10),Fas-ligand+TNF-α group (n =5) and Fas-ligand+TNF-α+LXA4 group (n=5).Cells were incubated with 100 ng/ml Fas-Ligand,100 ng/ml Fas-Ligand plus 100 nmol/L LXA4,100 ng/ml Fas-Ligand plus 100 ng/ml TNF-α,and 100 ng/ml Fas-Ligand plus 100 ng/ml TNF-α plus 100 nmol/L LXA4 in Fas-ligand,Fas-ligand+LXA4,Fas-ligand+TNF-α,and Fas-ligand +TNF-α+LXA4 groups,respectively.The cell viability was measured at 24 h of culture or incubation.Cell apoptosis was detected using the flow cytometry,and apoptosis rate was calculated in C,Fas-ligand and Fas-ligand+LXA4 groups.Results Experiment Ⅰ Compared with group C,the percentage of cell repair size and percentage of proliferation were significantly increased in L1,L2 and L3 groups (P＜0.05 or 0.01).Compared with group L1,the percentage of cell repair size and percentage of proliferation were significantly increased in group L3 (P＜ 0.01),and no significant change was found in the parameters mentioned above in group L2 (P＞0.05).Experiment Ⅱ Compared with group C,the cell viability was significantly decreased,and the apoptosis rate was increased in group Fas-ligand,the cell viability was significantly decreased in group Fas-ligand+TNF-α (P＜ 0.01),and no significant change was found in the cell viability or apoptosis rate in group Fas-ligand+LXA4 or in the cell viability in group Fas-ligand+TNF-α+LXA4 (P＞0.05).Compared with group Fas-ligand,the cell viability was significantly increased,and the apoptosis rate was decreased in group Fas-ligand+LXA4 (P＜ 0.05).The cell viability was significantly higher in group Fas-ligand +TNF-α + LXA4 than in group Fas-ligand +TNF-α (P ＜ 0.01).Conclusion LXA4 can promote human type Ⅱ alveolar epithelial cell wound repair and proliferation and inhibit the apoptosis.

Objective To explore the effects of lipoxinA4 on expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in rat primary lung fibroblast cells (LF) after lipopolysaccharide (LPS) challenge.Methods Primary lung fibroblast cells were incubated with various concentrations (0.1,1,10 μg/mL) of LPS for different lengths of time (3,6,9 h).Then primary lung fibroblast cells were still incubated in DMEM medium containing LPS in the presence or absence of lipoxinA4.After incubation,the supematant of medium was collected and the level of PGE2 was detected by using ELISA.The cells were harvested,and COX-2 protein was analyzed by Western blot.Results The model of acute inflammation in fibroblasts was well established by administering 1 μg/mL LPS in fibroblasts for 6 hours.Induction of COX-2 protein by LPS was inhibited by lipoxinA4.The levels of PGE2 in control group,LPS group and LPS + LipoxinA4 group were 55.84 pg/mL,411.73 pg/mL and 307.07 pg/mL,respectively,and there was a significantdifference between LPS group and LPS + LipoxinA4 group (P ＜0.01).Conclusion LipoxinA4 down-regulates the expression of the COX-2 induced by LPS in primary lung fibroblast cells and consequently inhibits the production of PGE2 in a dose dependent manner.

BACKGROUNDCollaterals to occluded infarct-related coronary arteries (IRA) have been observed after the onset of acute ST-elevation myocardial infarction (STEMI). We sought to investigate the impact of early coronary collateralization, as evidenced by angiography, on myocardial reperfusion and outcomes after primary percutaneous coronary intervention (PCI).

METHODSAcute procedural results, ST-segment resolution (STR), enzymatic infarct size, echocardiographic left ventricular function, and major adverse cardiac events (MACE) at 6-month follow-up were assessed in 389 patients with STEMI undergoing primary PCI for occluded IRA (TIMI flow grade 0 or 1) within 12 hours of symptom-onset. Angiographic coronary collateralization to the occluded IRA at first contrast injection was graded according to the Rentrop scoring system.

RESULTSLow (Rentrop score of 0 or 1) and high (Rentrop score of 2 or 3) coronary collateralization was detected in 329 and 60 patients, respectively. Patients with high collateralization more commonly had prior stable angina and right coronary artery occlusion, but less often had left anterior descending artery occlusion. At baseline, these patients presented with less extent of ST-segment elevation and lower serum levels of creatine kinase myocardial band (CK-MB) and cardiac troponin I (cTnI). Procedural success rate, STR, corrected TIMI flame count, and area under the curve of CK-MB and cTnI measurements after the procedure were similar between patients with high collateralization and those with low collateralization (for all comparisons P > 0.05). There were no differences in left ventricular ejection fraction and rates of MACE at 6 months according to baseline angiographic collaterals to occluded IRA.

CONCLUSIONSIn patients with acute STEMI undergoing primary PCI within 12 hours of symptom-onset, coronary collateralization to the occluded IRA was influenced by clinical and angiographic features. Early recruitment of collaterals limits infarct size at baseline, but has no significant impact on myocardial reperfusion after the procedure and subsequent left ventricular function and clinical outcomes.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; therapy ; Treatment Outcome ; Young Adult