Periodontitis is a chronic inflammatory disease, and its occurrence and development are closely related to the imbalance of local innate immune responses. The caspase family plays a crucial role in regulating inflammatory responses and cell death pathways in periodontal innate immune cells (such as gingival epithelial cells, neutrophils, macrophages, dendritic cells, and natural killer cells). These proteases exhibit a dual regulatory effect on cellular functions. On one hand, apoptotic pathways mediated by caspase-3/7/9 enable the programmed clearance of senescent or damaged cells, while pyroptosis pathways mediated by caspase-1/4 contribute to immune defense and pathogen elimination, collectively helping to maintain tissue homeostasis. On the other hand, excessive activation of the caspase-1/gasdermin D pathway, as well as inflammatory amplification pathways involving caspase-4/6/8, promotes the release of inflammatory cytokines such as IL-1β and IL-18, leading to the disruption of the epithelial barrier and exacerbation of periodontal tissue damage. Caspase regulation exhibits both commonality and cell specificity. In gingival epithelial cells, caspase-1 mediates pyroptosis and inflammation activation, caspase-3 regulates apoptosis and proliferation signaling, and caspase-4 participates in differentiation regulation and pathogen-selective immune responses, collectively adapting to physiological and pathological changes. Neutrophils can utilize the caspase-1/gasdermin D signaling pathway to drive the release of neutrophil extracellular traps without triggering typical pyroptosis. In macrophages, caspase-1 and caspase-8 synergistically promote polarization toward the M1 phenotype, while caspase-3 acts as an apoptosis executor to facilitate macrophage transition to the M2 phenotype in specific microenvironments. This article reviews caspase’s specific mechanism of action in periodontal innate immune-related cells, aiming to provide a new theoretical basis for targeted regulation of caspase in the treatment of periodontitis.

OBJECTIVES: To explore the promoting effect of ginsenoside Rb3 (Rb3) on osteogenesis in periodontitis environment, and to explain its mechanism. METHODS: Human periodontal ligament stem cells (hPDLSCs) were cultured by tissue block method and identified by flow cytometry. Cell counting kit-8 (CCK8) method and calcein acetoxymethyl ester/propidium iodide staining were used to detect the effect of Rb3 on the viability of hPDLSCs cells. In vitro cell experiments were divided into control group, 10 μg/mL lipopolysaccharides (LPS) group, 10 μg/mL LPS+100 μmol/L Rb3 group and 10 μg/mL LPS+200 μmol/L Rb3 group. Alkaline phosphatase (ALP) staining was used to detect the ALP activity of hPDLSCs in each group after osteogenesis induction. The expression of hPDLSCs interleukin-6 (IL-6), interleukin-8 (IL-8), runt-related transcription factor 2 (RUNX2) and transforming growth factor-β (TGF-β)genes in each group after osteogenesis was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. Western blot was used to detect the protein expression of hPDLSCs phosphorrylated extracellular signal-regulated kinase (p-ERK) in each group. Sprague-Dawley rats were randomly divided into the control group, ligation group and ligation+Rb3 group. The left molar-maxillary tissue was subjected to micro-computed tomography (micro-CT) scanning. After the scanning, the left molar-maxilla was made into periodontal tissue sections. Hematoxylin-eosin (HE) staining was used to detect the infiltration and loss of adhesion of inflammatory cells. Masson staining was used to detect the destruction of gingival collagen fibers. Immunofluorescence staining was used to detect the protein expression of RUNX2 and p-ERK. The expression of TGF-β in rat gingival tissue was detected by qRT-PCR. The protein expression of IL-6 in peripheral serum of rats was detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of Treg cells in rat heart blood. The experimental data were statistically analyzed by Graph Pad Prism10.1.2 software. RESULTS: Rb3 had no effect on the cell activity of hPDLSCs. The results of qRT-PCR and ALP staining showed that Rb3 could inhibit the gene expression of IL-6 and IL-8 in inflammatory hPDLSCs, promote TGF-β gene and promote the osteogenic differentiation of inflammatory hPDLSCs. Western blot showed that Rb3 inhibited the protein expression of inflammatory hPDLSCs p-ERK. The results from micro-CT, Masson staining, and HE staining demonstrated that Rb3 promotes alveolar bone formation in rats with periodontitis, while simultaneously inhibiting the destruction of periodontal fibrous tissue, reducing attachment loss, and suppressing inflammatory cell infiltration. The results of flow cytometry showed that Rb3 could promote the differentiation of Treg cells in peripheral blood of periodontitis rats. The results of ELISA and qRT-PCR showed that Rb3 could inhibit the protein expression of IL-6 and promote the gene expression of TGF-β in periodontitis rats. Immunofluorescence results showed that Rb3 could promote the protein expression of RUNX2 and inhibit the protein expression of p-ERK in periodontitis rats. CONCLUSIONS Rb3 can reduce the inflammatory reaction of periodontal tissues in periodontitis rats, and promote the osteogenic differentiation of hPDLSCs by regulating p-ERK pathways.
Animals ; Ginsenosides/pharmacology* ; Osteogenesis/drug effects* ; Periodontitis/metabolism* ; Rats ; Periodontal Ligament/cytology* ; Humans ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Stem Cells/drug effects* ; Interleukin-6/metabolism* ; Rats, Sprague-Dawley ; Interleukin-8/metabolism* ; Cells, Cultured ; MAP Kinase Signaling System/drug effects* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Male ; Phosphorylation ; Lipopolysaccharides ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Alkaline Phosphatase/metabolism*

Objective To investigate the effects of low background radiation environments in deep underground settings on the biological behavior of NP69 human nasopharyngeal epithelial cells(NP69 cells)and the underlying molecular mechanisms.Methods A parallel control experimental design was adopted and NP69 cells were synchronously cultured in settings of three underground depths at the China in situ Deep-Underground Facility&Life Observatory(DeUFO)—ground level(DeUFO-0 m),1 000 m underground(DeUFO-1 000 m),and 1 500 m underground(DeUFO-1 500 m).Changes in cell proliferation and migration capabilities were assessed using the Cell Counting Kit-8(CCK-8)assay and scratch assay,respectively.High-throughput RNA sequencing(RNA-Seq)was performed to identify differentially expressed genes(DEGs).Functional annotation and pathway enrichment analysis of the DEGs were performed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.Results CCK-8 assay revealed that,after 72 h of culture,the absorbance value of the DeUFO-0 m group was 1.35 times and 1.27 times those of the those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).After 96 h of culture,the absorbance value of the DeUFO-0 m group was 1.52 times and 1.41 times those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).Colony formation assays revealed that the number of cell colonies in the DeUFO-0 m group was 1.59 times and 1.27 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.001).The scratch assay revealed that the 36-hour wound healing rate of the DeUFO-0 m group was 2.22 times and 4.00 times those of the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transwell assays revealed that the number of migrating cells in the DeUFO-0 m group was 2.08 times and 2.56 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transcriptome sequencing analysis revealed consistent upregulation of CELF2,CELF4,CGB8,GRHL2,and DMRTA2 genes in the DeUFO-1 000 m and DeUFO-1 500 m groups.Pathway enrichment analysis indicated significant enrichment of extracellular matrix(ECM)remodeling-associated pathways and gene expression regulation pathways in the experimental groups(false discovery rate[FDR]<0.05).Conclusion The low background radiation environment in deep underground settings suppresses the proliferation and migration activities of NP69 cells by mediating ECM remodeling and post-transcriptional regulatory mechanisms through the regulation of target genes such as the CELF family.This study provides experimental evidence for establishing a dose-response relationship between environmental radiation and cellular effects.

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.

Objective To explore the prescription and preparation technology of compound Bupleurum suppository and draft its quality standard.Methods The volatile oil of Bupleurum was extracted by steam distillation,and the compound Bupleurum-based suppository was prepared by mixing the volatile oil with taurine using the melting method.The quality standard of the preparation was formulated according to the quality inspection items of the general rule 0107 of the Pharmacopoeia of the People's Republic of China(2020 Edition,Volume IV);The contents of n-hexanoic acid and n-heptanoic acid in the preparation were determined by gas chromatography-mass spectrometry(GC-MS).The content of taurine in the preparation was determined by high-performance liquid chromatography(HPLC).Results The optimized distillation time of the volatile oil was 1.5 h,The linear ranges of n-hexanoic acid,n-heptanoic acid and taurine are 23.175 0-115.875 0 μg·mL-1(R2=0.999 4),4.590 0-68.850 0 μg·mL-1(R2=0.998 9)and 15-125 μg·mL-1(R2=0.999 6),respectively.The average recoveries are 99.83%,101.96%,98.89%with RSDs of 2.84%,1.36%,2.88%,respectively.The RSDs of precision,stability,and repeatability tests are less than 5%.The properties,mass difference,melting time,microbial limit,and stability assessment of the preparationwere all in accordance with the Pharmacopoeia of the People's Republic of China.Conclusion Compound Bupleurum suppository preparation technology is reasonable and feasible,which meets the quality standard.

Objective To explore the prescription and preparation technology of compound Bupleurum suppository and draft its quality standard.Methods The volatile oil of Bupleurum was extracted by steam distillation,and the compound Bupleurum-based suppository was prepared by mixing the volatile oil with taurine using the melting method.The quality standard of the preparation was formulated according to the quality inspection items of the general rule 0107 of the Pharmacopoeia of the People's Republic of China(2020 Edition,Volume IV);The contents of n-hexanoic acid and n-heptanoic acid in the preparation were determined by gas chromatography-mass spectrometry(GC-MS).The content of taurine in the preparation was determined by high-performance liquid chromatography(HPLC).Results The optimized distillation time of the volatile oil was 1.5 h,The linear ranges of n-hexanoic acid,n-heptanoic acid and taurine are 23.175 0-115.875 0 μg·mL-1(R2=0.999 4),4.590 0-68.850 0 μg·mL-1(R2=0.998 9)and 15-125 μg·mL-1(R2=0.999 6),respectively.The average recoveries are 99.83%,101.96%,98.89%with RSDs of 2.84%,1.36%,2.88%,respectively.The RSDs of precision,stability,and repeatability tests are less than 5%.The properties,mass difference,melting time,microbial limit,and stability assessment of the preparationwere all in accordance with the Pharmacopoeia of the People's Republic of China.Conclusion Compound Bupleurum suppository preparation technology is reasonable and feasible,which meets the quality standard.

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.

Objective:Through comprehensive analysis of symptoms and signs, biochemistry, imaging, and dynamic tests, to explore the diagnosis and differential diagnosis of thyrotropin-secreting pituitary adenoma(TSH adenoma) and syndrome of resistance to thyroid hormone(RTH).Methods:A retrospective analysis was conducted on clinical data from 14 patients who visited the First Affiliated Hospital of Zhengzhou University from July 2016 to September 2022, exhibiting elevated levels of free thyroxine(FT4) and free triiodothyronine(FT3) in the presence of increased TSH.Results:There were 7 cases of TSH adenoma and 7 cases of RTH, with the average age of diagnosis at 40.0 years and 26.6 years, respectively. Thirteen patients showed thyrotoxicosis or occasional palpitation, some with pituitary occupancy manifestations or abnormal growth and development; One patient presented with neck thickening. Sex hormone binding globulin was elevated in 3 cases of TSH adenoma. Pituitary magnetic resonance imaging showed that all 7 cases of TSH adenoma were macroadenomas and 1 case of RTH was microadenoma. The octreotide suppression test in 13 patients was inhibited, but there was a significant difference in the inhibition rate of 24 h/2 h TSH inhibition rate of TSH adenoma and RTH, ranging from 46.6% to 83.9% and 4.6% to 28.8% respectively. Six cases of RTH had thyroid hormone receptor β mutation.Conclusion:Syndrome of inappropriate secretion of thyrotropin is a rare condition, mainly including TSH adenoma and RTH. The diagnosis and differentiation of the two conditions require comprehensive assessment incorporating family history, symptoms and signs, laboratory tests, dynamic test, and genetic test. Among these, the 24 h/2 h TSH inhibition rate of octreotide suppression test can effectively distinguish TSH adenoma from RTH.

This article presents a case of primary hypomagnesemia with secondary hypocalcemia in an adult. The patient′s medical history and treatment were reviewed. Following oral magnesium supplementation, the patient′s clinical symptoms improved and the blood magnesium level increased. This report aims to raise clinical awareness of primary hypomagnesia with secondary hypocalcemia.

Objective:To explore the independent risk factor for in-hospital mortality of patients with multiple trauma, and to construct a prediction model of risk of death and validate its efficacy.Methods:A retrospective cohort study was performed to analyze the clinical data of 1 028 patients with multiple trauma admitted to Affiliated Hospital of Jiangsu University from January 2011 to December 2021. There were 765 males and 263 females, aged 18-91 years[(53.8±12.4)years]. The injury severity score (ISS) was 16-57 points [(26.3±7.6)points]. There were 153 deaths and 875 survivals. A total of 777 patients were enrolled as the training set from January 2011 to December 2018 for building the prediction model, while another 251 patients were enrolled as validation set from January 2019 to December 2021. According to the outcomes, the training set was divided into the non-survival group (115 patients) and survival group (662 patients). The two groups were compared in terms of the gender, age, underlying disease, injury mechanism, head and neck injury, maxillofacial injury, chest injury, abdominal injury, extremity and pelvis injury, body surface injury, damage control surgery, pre-hospital time, number of injury sites, Glasgow coma score (GCS), ISS, shock index, and laboratory test results within 6 hours on admission, including blood lactate acid, white blood cell counts, neutrophil to lymphocyte ratio (NLR), platelet counts, hemoglobin, activated partial thromboplastin time (APTT), fibrinogen, D-dimer and blood glucose. Univariate analysis and multivariate Logistic regression analysis were performed to determine the independent risk factors for in-hospital mortality in patients with multiple trauma. The R software was used to establish a nomogram prediction model based on the above risk factors. Area under the receiver operating characteristic (ROC) curve (AUC), calibration curve and clinical decision curve analysis (DCA) were plotted in the training set and the validation set, and Hosmer-Lemeshow goodness-of-fit test was performed.Results:Univariate analysis showed that abdominal injury, extremity and pelvis injury, damage control surgery, GCS, ISS, shock index, blood lactic acid, white blood cell counts, NLR, platelet counts, hemoglobin, APTT, fibrinogen, D-dimer and blood glucose were correlated with in-hospital mortality in patients with multiple trauma ( P<0.05 or 0.01). Logistic regression analysis showed that GCS≤8 points ( OR=1.99, 95% CI 1.12,3.53), ISS>25 points ( OR=7.39, 95% CI 3.50, 15.61), shock index>1.0 ( OR=3.43, 95% CI 1.94,6.08), blood lactic acid>2 mmol/L ( OR=9.84, 95% CI 4.97, 19.51), fibrinogen≤1.5 g/L ( OR=2.57, 95% CI 1.39,4.74) and blood glucose>10 mmol/L ( OR=3.49, 95% CI 2.03, 5.99) were significantly correlated with their in-hospital mortality ( P<0.05 or 0.01). The ROC of the nomogram prediction model indicated that AUC of the training set was 0.91 (95% CI 0.87, 0.93) and AUC of the validation set was 0.90 (95% CI 0.84, 0.95). The calibration curve showed that the predicted probability was consistent with the actual situation in both the training set and validation set. DCA showed that the nomogram prediction model presented excellent performance in predicting in-hospital mortality. In Hosmer-Lemeshow goodness-of-fit test, χ2 value of the training set was 9.69 ( P>0.05), with validation set of 9.16 ( P>0.05). Conclusions:GCS≤8 points, ISS>25 points, shock index>1.0, blood lactic acid>2 mmol/L, fibrinogen≤1.5 g/L and blood glucose>10 mmol/L are independent risk factors for in-hospital mortality in patients with multiple trauma. The nomogram prediction model based on these 6 predictive variables shows a good predictive performance, which can help clinicians comprehensively assess the patient′s condition and identify the high-risk population.