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.

Objective:To analyze the diagnostic value of inflammatory markers, clinical characteristics of patients with different prognoses, and variations in antimicrobial susceptibility testing for Klebsiella pneumoniae bloodstream infection. Methods:This study involved 166 patients with positive blood cultures for Klebsiella pneumoniae from January 2018 to May 2023 as the Klebsiella pneumoniae-positive group, and 100 patients with negative blood culture results as the negative group. The diagnostic value of inflammatory markers for Klebsiella pneumoniae bloodstream infection was evaluated through receiver operating characteristic (ROC) curve. The differences in C-reactive protein (CRP) and procalcitonin (PCT) levels between Klebsiella pneumoniae bloodstream infections and non- Klebsiella pneumoniae bloodstream infections were analyzed. According to the prognoses, 166 patients with Klebsiella pneumoniae bloodstream infection were divided into two groups: favorable outcome group (105 cases) and adverse outcome group (61 cases). Clinical features, infection sites, empirical use of antibiotics, and antimicrobial susceptibility were compared between the patients with different outcomes. Results:The percentage of neutrophils ( Z=-3.645, P<0.001), CRP level ( Z=-6.809, P<0.001), and PCT level ( Z=-8.214, P<0.001) were significantly higher in the Klebsiella pneumoniae-positive group than in the negative group. The area under the ROC curve (AUC) values for CRP and PCT in diagnosing Klebsiella pneumoniae bloodstream infection were 0.755 and 0.849, respectively. There were variations in CRP ( H=20.902, P<0.001) and PCT ( H=33.521, P<0.001) levels among patients with bloodstream infection caused by Klebsiella pneumoniae, other common negative bacilli, common positive cocci, or Candida. The body temperature, albumin level, hemoglobin level, and length of hospital stay in the adverse outcome group were lower than those in the favorable outcome group ( P<0.05). Besides, the incidence of invasive operation, organ failure, shock, and rescue were also lower in the adverse outcome group ( P<0.05). In the adverse outcome group, co-infections mainly involved respiratory infections, accounting for 60.7% (37/61). Respiratory infections (49.5%, 52/105) were also the predominant co-infections in the favorable outcome group, followed by hepatobiliary infections (34.3%, 36/105). The pathogenic bacteria cultured from different infection sites were mainly Klebsiella pneumoniae. In the favorable outcome group, fluoroquinolones were the most commonly used medications for empirical therapy, with a usage rate of 76.2% (80/105), followed by β-lactamase inhibitor complex preparations (68.6%, 72/105), the usage rate of which were significantly higher than those in the adverse outcome group ( P<0.05). Carbapenems were the preferred drugs for the adverse outcome group, with a usage rate of up to 62.3% (38/61), which was significantly higher than that in the favorable outcome group ( P<0.05). The adverse outcome group showed high resistance rates to ciprofloxacin (40.98%, 25/61) and levofloxacin (37.7%, 23/61), while the resistance rates were 22.86% (24/105) and 32.38% (34/105) in the favorable outcome group. The resistance rates to other drugs were low and there was no significant difference between the two groups ( P>0.05). Conclusions:PCT and CRP have certain value in diagnosing bloodstream infections caused by Klebsiella pneumoniae, and have certain reference significance for differentiating bloodstream infections caused by Gram-negative bacteria, Gram-positive bacteria, and Candida species. The source of bloodstream infection in patients with adverse outcome may be the respiratory system, while in patients with favorable outcome, the main sources of bloodstream infection may be the respiratory and hepatobiliary systems. Antimicrobial susceptibility testing reveals the highest resistance rate to fluoroquinolones. Given their frequent use in empirical therapy, this may lead to treatment failure. Notably, carbapenems are more commonly administered as empirical antibiotics in the adverse outcome group.

Objective:To investigate the risk factors associated with 90-day mortality in critically ill patients receiving continuous renal replacement therapy (CRRT), with a particular focus on the association between hypotension within the first hour of CRRT initiation and 90-day mortality after hospital admission.Methods:This study was a post hoc analysis of a prospective cohort study investigating the impact of colloid versus crystalloid priming solutions on early hemodynamics in critically ill patients undergoing CRRT. The study enrolled intensive care unit patients who received CRRT at West China Hospital of Sichuan University from January 2024 to May 2024. The data were collected including demographic characteristics, laboratory tests, CRRT-related parameters, blood pressure, heart rate, sequential organ failure assessment scores, and vasoactive-inotropic score, etc. The 90-day survival outcome after hospital admission of critically ill patients aged 18-80 years who received continuous veno-venous hemodiafiltration was used as the primary outcome indicator. A Cox proportional hazards model analysis was conducted, and the predictive ability of the model was evaluated along with the test of the proportional hazards assumption. The risk factors associated with the 90-day mortality after hospital admission of critically ill patients receiving CRRT were explored, with a particular focus on whether hypotension occurring within the first hour of CRRT initiation was one of these risk factors.Results:A total of 208 patients were included in this study. Within 90 days after hospital admission, 141 patients (67.8%) died, among whom 102 were male (72.3%) and the median age was 61.0 (50.0, 71.5) years; 67 patients (32.2%) survived, among whom 53 were males (79.1%) and the median age was 56.0 (47.0, 68.0) years. The incidence of hypotension within the first hour of CRRT initiation was significantly higher in the death group than in the survival group [29.8% (42/141) vs. 16.4% (11/67), χ2=4.275, P=0.039]. Moreover, The mortality rate of the group with hypotension within the first hour of CRRT initiation was higher than that of the group without hypotension [79.2% (42/53) vs. 63.9% (99/155), χ2=4.275, P=0.039]. The Kaplan-Meier survival analysis showed that the median survival time of patients without hypotension within the first hour of CRRT initiation [39.0 d (95% CI 23.2-54.8)] was longer than that of patients with hypotension [26.0 d (95% CI 18.9-33.1)], and the 90-day cumulative survival rate after hospital admission of patients without hypotension was significantly higher than that of patients with hypotension (Log-rank test, χ2=5.100, P=0.024). Univariate and multivariate Cox proportional hazards analyses demonstrated that serum albumin ( HR=0.964, 95% CI 0.933-0.997, P=0.030), sequential organ failure assessment score ( HR=1.064, 95% CI 1.012-1.118, P=0.015), and the use of mechanical ventilation ( HR=8.272, 95% CI 1.145-59.743, P=0.036) were significantly associated with 90-day mortality in critically ill patients undergoing CRRT. In contrast, the vasoactive-inotropic score ( HR=1.004, 95% CI 0.999-1.008, P=0.079) and the presence of hypotension within the first hour of CRRT initiation ( HR=1.236, 95% CI 0.833-1.835, P=0.293) were not significantly associated with 90-day mortality in critically ill patients undergoing CRRT. The consistency index of this model was 0.654 (95% CI 0.617-0.691), the area under the receiver operating characteristic curve was 0.724 (95% CI 0.658-0.800), and the calibration curve showed that the predicted values of the model were well fitted to the actual observations, suggesting that the predictive effect of this model was relatively ideal. Conclusions:In critically ill patients undergoing CRRT, the occurrence of hypotension within the first hour of CRRT initiation was not significantly associated with 90-day mortality after hospital admission. Lower serum albumin levels, higher sequential organ failure assessment scores, and the use of mechanical ventilation may be the risk factors for 90-day mortality in this population.

Objective To investigate the characteristics of epilepsy onset based on the theory of five circuits and six qi in traditional Chinese medicine(TCM).Methods A total of 8 389 epilepsy patients from a community-based natural population cohort study from UK Biobank were included.Frequency and constituent ratio analyses were performed to describe the distribution of epilepsy onset in relation to the five circuits and six qi elements,and statistical inferences were made using chi-square tests.Results The analysis revealed statistically significant differences existed in epilepsy onset across different heavenly stems,earthly branches,recombinant yearly circuit,celestial control and terrestrial effect,and dominant qi(all P＜0.05).From the perspective of circuits,the highest incidence occurred in years corresponding to the"Ji"and"Hai"years,while the lowest incidence was observed in"Bing"and"Mao"years.Years dominated by wood circuit and wind manifestations exhibited the highest incidence,whereas years with cold manifestations showed the lowest incidence,suggesting the liver as the primary pathological site in epilepsy.From the perspective of qi,the third dominant qi was most frequently associated with onset.Regarding presiding and subordinate qi,years with taiyin damp earth presiding and taiyang cold water subordinate had the highest incidence,while years with yangming dry metal presiding and shaoyang monarch fire subordinate had the lowest incidence,indicating that cold-damp years and midsummer periods are potential triggers for epilepsy.Conclusion There is a certain regularity in the epilepsy onset correlated with the features of five circuits and six qi,which can guide prevention and clinical diagnosis and treatment of epilepsy.

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.

Objective:To analyze the diagnostic value of inflammatory markers, clinical characteristics of patients with different prognoses, and variations in antimicrobial susceptibility testing for Klebsiella pneumoniae bloodstream infection. Methods:This study involved 166 patients with positive blood cultures for Klebsiella pneumoniae from January 2018 to May 2023 as the Klebsiella pneumoniae-positive group, and 100 patients with negative blood culture results as the negative group. The diagnostic value of inflammatory markers for Klebsiella pneumoniae bloodstream infection was evaluated through receiver operating characteristic (ROC) curve. The differences in C-reactive protein (CRP) and procalcitonin (PCT) levels between Klebsiella pneumoniae bloodstream infections and non- Klebsiella pneumoniae bloodstream infections were analyzed. According to the prognoses, 166 patients with Klebsiella pneumoniae bloodstream infection were divided into two groups: favorable outcome group (105 cases) and adverse outcome group (61 cases). Clinical features, infection sites, empirical use of antibiotics, and antimicrobial susceptibility were compared between the patients with different outcomes. Results:The percentage of neutrophils ( Z=-3.645, P<0.001), CRP level ( Z=-6.809, P<0.001), and PCT level ( Z=-8.214, P<0.001) were significantly higher in the Klebsiella pneumoniae-positive group than in the negative group. The area under the ROC curve (AUC) values for CRP and PCT in diagnosing Klebsiella pneumoniae bloodstream infection were 0.755 and 0.849, respectively. There were variations in CRP ( H=20.902, P<0.001) and PCT ( H=33.521, P<0.001) levels among patients with bloodstream infection caused by Klebsiella pneumoniae, other common negative bacilli, common positive cocci, or Candida. The body temperature, albumin level, hemoglobin level, and length of hospital stay in the adverse outcome group were lower than those in the favorable outcome group ( P<0.05). Besides, the incidence of invasive operation, organ failure, shock, and rescue were also lower in the adverse outcome group ( P<0.05). In the adverse outcome group, co-infections mainly involved respiratory infections, accounting for 60.7% (37/61). Respiratory infections (49.5%, 52/105) were also the predominant co-infections in the favorable outcome group, followed by hepatobiliary infections (34.3%, 36/105). The pathogenic bacteria cultured from different infection sites were mainly Klebsiella pneumoniae. In the favorable outcome group, fluoroquinolones were the most commonly used medications for empirical therapy, with a usage rate of 76.2% (80/105), followed by β-lactamase inhibitor complex preparations (68.6%, 72/105), the usage rate of which were significantly higher than those in the adverse outcome group ( P<0.05). Carbapenems were the preferred drugs for the adverse outcome group, with a usage rate of up to 62.3% (38/61), which was significantly higher than that in the favorable outcome group ( P<0.05). The adverse outcome group showed high resistance rates to ciprofloxacin (40.98%, 25/61) and levofloxacin (37.7%, 23/61), while the resistance rates were 22.86% (24/105) and 32.38% (34/105) in the favorable outcome group. The resistance rates to other drugs were low and there was no significant difference between the two groups ( P>0.05). Conclusions:PCT and CRP have certain value in diagnosing bloodstream infections caused by Klebsiella pneumoniae, and have certain reference significance for differentiating bloodstream infections caused by Gram-negative bacteria, Gram-positive bacteria, and Candida species. The source of bloodstream infection in patients with adverse outcome may be the respiratory system, while in patients with favorable outcome, the main sources of bloodstream infection may be the respiratory and hepatobiliary systems. Antimicrobial susceptibility testing reveals the highest resistance rate to fluoroquinolones. Given their frequent use in empirical therapy, this may lead to treatment failure. Notably, carbapenems are more commonly administered as empirical antibiotics in the adverse outcome group.

Objective:To investigate the risk factors associated with 90-day mortality in critically ill patients receiving continuous renal replacement therapy (CRRT), with a particular focus on the association between hypotension within the first hour of CRRT initiation and 90-day mortality after hospital admission.Methods:This study was a post hoc analysis of a prospective cohort study investigating the impact of colloid versus crystalloid priming solutions on early hemodynamics in critically ill patients undergoing CRRT. The study enrolled intensive care unit patients who received CRRT at West China Hospital of Sichuan University from January 2024 to May 2024. The data were collected including demographic characteristics, laboratory tests, CRRT-related parameters, blood pressure, heart rate, sequential organ failure assessment scores, and vasoactive-inotropic score, etc. The 90-day survival outcome after hospital admission of critically ill patients aged 18-80 years who received continuous veno-venous hemodiafiltration was used as the primary outcome indicator. A Cox proportional hazards model analysis was conducted, and the predictive ability of the model was evaluated along with the test of the proportional hazards assumption. The risk factors associated with the 90-day mortality after hospital admission of critically ill patients receiving CRRT were explored, with a particular focus on whether hypotension occurring within the first hour of CRRT initiation was one of these risk factors.Results:A total of 208 patients were included in this study. Within 90 days after hospital admission, 141 patients (67.8%) died, among whom 102 were male (72.3%) and the median age was 61.0 (50.0, 71.5) years; 67 patients (32.2%) survived, among whom 53 were males (79.1%) and the median age was 56.0 (47.0, 68.0) years. The incidence of hypotension within the first hour of CRRT initiation was significantly higher in the death group than in the survival group [29.8% (42/141) vs. 16.4% (11/67), χ2=4.275, P=0.039]. Moreover, The mortality rate of the group with hypotension within the first hour of CRRT initiation was higher than that of the group without hypotension [79.2% (42/53) vs. 63.9% (99/155), χ2=4.275, P=0.039]. The Kaplan-Meier survival analysis showed that the median survival time of patients without hypotension within the first hour of CRRT initiation [39.0 d (95% CI 23.2-54.8)] was longer than that of patients with hypotension [26.0 d (95% CI 18.9-33.1)], and the 90-day cumulative survival rate after hospital admission of patients without hypotension was significantly higher than that of patients with hypotension (Log-rank test, χ2=5.100, P=0.024). Univariate and multivariate Cox proportional hazards analyses demonstrated that serum albumin ( HR=0.964, 95% CI 0.933-0.997, P=0.030), sequential organ failure assessment score ( HR=1.064, 95% CI 1.012-1.118, P=0.015), and the use of mechanical ventilation ( HR=8.272, 95% CI 1.145-59.743, P=0.036) were significantly associated with 90-day mortality in critically ill patients undergoing CRRT. In contrast, the vasoactive-inotropic score ( HR=1.004, 95% CI 0.999-1.008, P=0.079) and the presence of hypotension within the first hour of CRRT initiation ( HR=1.236, 95% CI 0.833-1.835, P=0.293) were not significantly associated with 90-day mortality in critically ill patients undergoing CRRT. The consistency index of this model was 0.654 (95% CI 0.617-0.691), the area under the receiver operating characteristic curve was 0.724 (95% CI 0.658-0.800), and the calibration curve showed that the predicted values of the model were well fitted to the actual observations, suggesting that the predictive effect of this model was relatively ideal. Conclusions:In critically ill patients undergoing CRRT, the occurrence of hypotension within the first hour of CRRT initiation was not significantly associated with 90-day mortality after hospital admission. Lower serum albumin levels, higher sequential organ failure assessment scores, and the use of mechanical ventilation may be the risk factors for 90-day mortality in this population.

Objective:To identify and observe disease-causing gene variants and clinical phenotypes in a Han Chinese family with Leber congenital amaurosis (LCA).Methods:A retrospective study. A patient with LCA10 and his parents who had presented at Department of Ophthalmology of Henan Provincial People's Hospital on May 2022 were selected as the study subject. Detailed medical and family histories were recorded, fundus photography and flash electroretinogram (F-ERG) were performed. Peripheral venous blood samples (3 ml) of the proband and his parents were collected to extract whole genomic DNA, then whole exome sequencing (WES) and mitochondrial DNA (mtDNA) sequencing were carried out for the proband to determine the disease-causing gene and variants. All variants were annotated by bioinformatics analysis. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the pathogenicity of all detected variants were evaluated. Candidate variants were verified by Sanger sequencing, and in vitro minigene assay were performed to evaluate the impact of the missense variant with insufficient evidence on mRNA splicing.Results:The proband, male, 7-month-old, presented with an inability to follow light or objects, eye poking, photophobia, nystagmus, partial loss of retinal pigment epithelium around the fovea of the macula. At the age of 2 years old, F-ERG revealed severe reduction, elongation, or even no waveform of a-wave and b-wave in both eyes. No obvious abnormality was found in the clinical phenotype of his parents. The result of WES revealed that the proband carried two variants in exon 40 and exon 2 of CEP290, a frameshift variant c.5515_5518del (p.Glu1839Lysfs*11) (V1) and a novel missense variant c.74C>T (p.Ala25Val) (V2), respectively. The result of mitochondrial DNA sequencing was negative. Sanger sequencing confirmed that the heterozygous frameshift variant was inherited from his father and the heterozygous novel missense variant was inherited from his mother, which constituted compound heterozygous variants. In vitro minigene splicing assay confirmed that V2 created a new splicing donor at exon 2, leading to the in-frame deletion of 30bp fragment during transcription and loss of 10 amino acid residues in the protein. The two variants were pathogenic (V1) and likely pathogenic (V2) based on ACMG guidelines, respectively. Conclusions:The c.5515_5518del and novel c.74C>T compound heterozygous variants of the CEP290 gene probably are the cause of LCA10 in this family, which lead to the production of a truncated protein and aberrant splicing of pre-mRNA, respectively. LCA is characterized by early onset, severe impairment of visual function, and a wide range of disease-causing variations.

Building a nationwide representative sibling information database of pediatric cancer is of great significance for the research of pediatric cancer. In October 2022, based on the national pediatric cancer surveillance platform, the National Center for Pediatric Cancer Surveillance(NCPCS) identified and integrated the information of pediatric cancer cases using the patient master index, and then determined and retrieved the diagnosis and treatment information of pediatric cancer siblings through the sibling pair matching algorithm system, to establish the sibling information database. The information database was stored in the sibling database module of the surveillance platform, which realized the dynamic update, retrieval, download, and analysis of sibling information. The database provided data and technical support for the further childhood cancer research among siblings, as well as provided a reference for the construction of research-oriented databases for other disease surveillance systems. As of March 2024, this database had included 2 980 childhood cancer patients, collecting nearly 30 000 related medical records. In the future, NCPCS should further improve the sensitivity of sibling decision logic and expand the functionality of the sibling information database, so as to better meet the diverse needs of clinical and scientific research.