Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

Objective: To investigate the seroepidemiological characteristics of hepatitis B among outpatients in medical institutions in Jiaxing City, Zhejiang Province, so as to provide a reference for formulating region-specific hepatitis B prevention and control strategies. Methods: From April to June 2024, outpatients were selected as study subjects from sentinel medical institutions in Jiaxing City. Information such as gender and age was collected. Venous blood samples were obtained and serological markers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb) were tested. Positive rates of hepatitis B virus (HBV) serological markers were analyzed by genders and ages. Results: A total of 1 468 outpatients were included, among whom 721 were males (49.11%) and 747 were females (50.89%). The mean age was (46.41±19.66) years. The positive rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb were 7.29%, 44.75%, 1.84%, 23.50%, and 42.03%, respectively. The HBcAb positive rate in males was significantly higher than in females (46.05% vs. 38.15%, P<0.05), while no statistically significant gender differences were observed in the positive rates of other four HBV serological markers (all P>0.05). Except for HBsAb, the positive rates of the other four HBV serological markers showed statistically significant differences across different age groups (all P<0.05). Pairwise comparisons results showed that the HBsAg positive rates in age groups of 20-<40 years and 40-<60 years were 9.48% and 9.57%, respectively, which were higher than those in age groups of <20 years (1.43%) and &ge;60 years (2.75%) (all P<0.05). A total of 17 HBV serological marker patterns were observed, among which the proportion of all markers negative was the highest, at 39.65%. The proportions of "small three positive" (HBsAg+, HBeAb+, HBcAb+) and "large three positive" (HBsAg+, HBeAg+, HBcAb+) patterns were 4.77% and 1.50%, respectively. Among HBsAg-positive individuals, the proportions of the "small three positive" pattern across age groups were 0, 45.45%, 90.00%, and 81.82%, while those of the "large three positive" were 0, 36.36%, 5.00%, and 0, with statistically significant differences across age groups (both P<0.05). Conclusions The positive rate of HBsAg among outpatients in medical institutions in Jiaxing City is relatively high, with a notable proportion of individuals showing either no immunity or non-response to vaccination. It is recommended to strengthen hepatitis B immunization efforts among the population aged 20-<60 years, and to enhance monitoring and interventional treatment for "small three positive" and "large three positive" patterns.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (&ge; 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (&ge; 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.

OBJECTIVE To explore the role of clinical pharmacists participating in the standardized perioperative nutritional management process for pancreaticoduodenectomy （PD） on improving postoperative recovery in patients. METHODS The clinical data of 100 patients undergoing PD in the Department of Biliary and Pancreatic Surgery， Drum Tower Hospital Affiliated to Nanjing University School of Medicine from November 2019 to February 2021 were analyzed retrospectively. According to the different perioperative nutrition management plans， they were divided into clinical pharmacist intervention group （n＝51， clinical pharmacists intervened according to the standardized nutrition management process） and control group （n＝49， clinical pharmacists only performed preoperative nutrition evaluation， and clinical physicians took nutrition support according to the patient’s condition）. The differences in postoperative recovery index， economic evaluation index， hospitalization length， postoperative complications， and postoperative enteral nutrition support route were compared between 2 groups. RESULTS The time of postoperative diet， the first postoperative ventilation， the first postoperative defecation， and postoperative drainage time of abdominal drain were significantly earlier in the clinical pharmacist intervention group than in the control group （P＜0.05）； the hospitalization cost， medication cost， nutritional support cost， parenteral nutrition cost， albumin preparation cost， and the length of postoperative hospitalization were significantly lower/shorter in the clinical pharmacist intervention group than in the control group （P＜0.05）； there was no statistically significant difference in the incidence of postoperative complications between the two groups （P＞0.05）； there was statistically significant difference in the perioperative enteral nutrition support pathways between two groups （P＜0.05）. CONCLUSIONS Clinical pharmacists’ participation in perioperative nutritional management for PD can significantly reduce hospitalization costs and nutritional support costs， improve patients’ perioperative nutritional status， and shorten hospital stays. wanglina668@163.com

ObjectiveTo analyze the epidemiological characteristics and related factors of pesticide poisoning occurred in daily life in Tiantai County, Zhejiang Province from 2015 to 2023, and to provide a basis for the prevention and control of pesticide poisoning. MethodsThe information of pesticide poisoning cases was obtained from the occupational disease and occupational health information monitoring system of the China Disease Prevention and Control Information System, death data was obtained from the Zhejiang Province Chronic Disease Surveillance Information Management System, so that the poisoning incidence rate and the fatality rate were analyzed. ResultsA total of 439 cases of pesticide poisoning occurred in life were reported in Tiantai County from 2015 to 2023, of which mainly concentrated in the second quarter of each year, with an average annual incidence rate of 10.62/10⁵ and fatality rate of 14.81%.The main cause of poisoning in < 15 years old group was accidental ingestion, while the main cause in ≥15 years old group was self-poisoning, and the difference was statistically significant (χ²＝103.518, P<0.001).The average annual incidence of pesticide poisoning occurred in life in the urban area was significantly lower than that in the rural area, and the difference was statistically significant (χ²＝30.871, P<0.001).The main types of pesticide poisoning were insecticides (65.15%), and paraquat had the highest fatality rate (47.73%). The results of binary logistic regression analysis indicated that age and types of pesticide poisoning may be the independent risk factors affecting the fatality of pesticide poisoning in daily life. ConclusionPesticide poisoning occurred frequently in Tiantai County over the years, and mainly occurred in summer, rural areas. Except for <15 years old group who were accidental ingestion,the other cases were mainly self-poisoning. The elderly and herbicide users should be the focus of key intervention targets. It is suggested to take personalized preventive and curative measures to intervene by age, seasons, regions and types to reduce the incidence and fatality rate of pesticide poisoning in daily life, and strengthen psychological health interventions to the cases of attempting to suicide.

The incidence of cancer is closely correlated with age,as 75％of non-small cell lung cancer(NSCLC)patients are aged at least 65 years.The availability of immune checkpoint inhibitors(ICIs)has altered the available NSCLC therapeutic pattern.Limited studies on elderly patients have demonstrated that ICIs as monotherapy provide substantial ben-efits for patients aged 65-75 years,showing no significant difference compared to younger patients.This benefit is also observed in combination with immune-combined chemotherapy or radiotherapy.For individuals older than 75 years,the survival effect was not evident,though.Immune-related adverse events(irAEs)with ICIs alone were similar in incidence across age catego-ries.Immune-combination chemotherapy resulted in a higher incidence of irAEs than chemotherapy alone,and patients &ge;75 years of age were more likely to experience higher-grade irAEs.Besides the fact that immunosenescence in older patients influ-ences the immune milieu in a multifaceted manner,which in turn impacts the effectiveness of immunotherapy,the prognosis is also influenced by the Eastern Cooperative Oncology Group performance status(ECOG PS)score,among other factors.For certain individuals aged &ge;75 years or in poor physical health,immunotherapy combined with low-intensity chemotherapy has emerged as a viable treatment option.However,there are fewer related studies,so there should be a conscious effort to increase the number of elderly patients enrolled in the trial and a comprehensive assessment to explore individualized treatment op-tions.To provide additional references and guidance for immunotherapy in elderly NSCLC patients and to propose new thera-peutic perspectives in combination with their characteristics,this review aims to summarize and analyze the pertinent studies on the application of programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)inhibitors in these patients.