Nuclear factor-kappa B （NF-κB） is an important intracellular transcription factor widely involved in the processes such as immune response， inflammatory response， cell proliferation， and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis， liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds， such as matrine and salvianolic acid B， have shown the potential in suppressing NF-κB activity， thereby exerting anti-inflammatory， anti-fibrotic， and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target， in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Objective To study the related molecular mechanism of andrographolide(AGP)in inhibi-ting the proliferation of human colon cancer LoVo cells and promoting their apoptosis.Methods The LoVo cells were set up as the control group and experimental group.The cells were treated with different concentra-tions of AGP(0,20,40,80 μmol/L).The cell viability was detected by CCK-8,the cellular cycle and apoptosis were detected by flow cytometery,and Western blot was used to detect protein level of PCNA,Bad and Bcl-2,and the effect of AGP of BMP9 overexpression or silencing AGP on PCNA,Bad and Bcl-2 protein levels;West-ern blot was used to analyze the effect of AGP on PTEN,Akt1/2/3 and p-Akt1/2/3 levels.Results AGP could inhibit the proliferation of LoVo cells,promoted their apoptosis and increased the BMP9 expression lev-el.The BMP9 overexpression could enhance the effect of AGP for inhibiting the proliferation and promoting the apoptosis,silencing BMP9 could weaken the above effects of AGP(P＜0.05).AGP decreased the expres-sion level of p-Akt1/2/3 in the LoVo cells and increased the PTEN expression level(P＜0.05).BMP9 over-expression enhanced AGP and decreased the p-Akt 1/2/3 expression level in the LoVo cells,and silencing BMP9 could weaken the above effects of AGP(P＜0.05).Conclusion AGP could inhibit the proliferation of human colon cancer LoVo cells,its mechanism may be related with up-regulating BMP9 expression,thus in-crease PTEN protein level and inhibit P13K/Akt signal.

Objective To analyze risk factors for sleep disorders in patients with chronic heart failure(CHF)and construct a nomogram prediction model.Methods Using simple random sampling,306 hospital-ized CHF patients meeting inclusion criteria were enrolled from four Grade A tertiary hospitals in Guangxi Zhuang Autonomous Region(two in Nanning,one each in Yulin and Guilin)between March 2023 and March 2024.LASSO regression analysis was initially employed for variable screening,followed by logistic regression to identify predictive variables for constructing the nomogram model.Model validation and performance evalua-tion were conducted using receiver operating characteristic(ROC)curves,calibration curves,and clinical decision curves,with internal validation performed through Bootstrap resampling(1 000 iterations).Results The incidence of sleep disorders among the 306 patients was 57.5%(176/306).Logistic regression analysis identified eight independent risk factors for sleep disorders in CHF patients(P＜0.05):age,education level,monthly house-hold income per capita,NYHA cardiac function classification,number of comorbidities,triglyceride levels,ano-rexia,and anxiety.The model demonstrated good discrimination for the AUC of 0.91(95%CI:0.77-0.88)and calibration consistency.Conclusion The prediction model established in this study shows good predictive performance,serving as a valuable reference for healthcare providers to early identify sleep disorders and im-plement preventive care strategies in patients with CHF.

Objective To investigate the effects of periodontitis induced by Prevotella nigrescens(Pn)combined with ligation on cognitive functions in mice.Methods Twenty-four C57BL/6J mice were randomly divided into control group,ligation group,and ligation+Pn treatment(P+Pn)group.Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks.After modeling,alveolar bone resorption was assessed using micro-CT and histological analysis.Learning and memory abilities of the mice were evaluated using open field test(OFT),novel object recognition test(NORT),and Morris water maze test(MWM).Seven weeks after the start of modeling,the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.Results After 6 weeks of molar ligation,micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice,and histological analysis showed apical migration of the junctional epithelium,epithelial ridge hyperplasia,and lymphocyte infiltration,and these changes were obviously worsened in P+Pn group.Alveolar bone height decreased significantly in both ligation groups compared to the control group.Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT,showed reduced novel object preference in NORT,and exhibited longer escape latencies in MWM,and the mice in P+Pn group had significantly poorer performances in the tests.Histologically,obvious neuronal cytoplasmic degeneration,necrosis,nuclear pyknosis,vacuolation,and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.Conclusion Pn infection aggravates alveolar bone destruction,accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.

Objective:To investigate the relationship between cardio-metabolic abnormalities in the first trimester and adverse pregnancy outcomes (APO).Methods:This cohort study recruited singleton pregnancies in the first trimester (6-13 +6 weeks of gestation) from Shenzhen Maternal and Child Health Care Hospital between January 1, 2021, and October 31, 2022. Cardiometabolic markers, including body mass index (BMI), blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were recorded during the first trimester. Incidence of APO, including gestational hypertension, preeclampsia, gestational diabetes mellitus, preterm birth, fetal growth restriction, small for gestational age infant, and placental abruption, was documented. Cardiovascular metabolic abnormalities in the first trimester were defined as meeting one or more of the following criteria: elevated BMI (BMI≥24 kg/m2), elevated TG (TG≥1.7 mmol/L), decreased HDL-C (HDL-C<1.0 mmol/L), elevated blood pressure (systolic pressure≥130 mmHg (1 mmHg=0.133 kPa) and/or diastolic pressure≥85 mmHg), elevated FPG (FPG≥5.6 mmol/L). Enrolled women were categorized into abnormal cardio-metabolic and normal cardio-metabolic groups. Poisson regression was employed to analyze the association between cardio-metabolic abnormalities in the first trimester and APO. Results:The study included 14 197 pregnant women with an age of (32.0±4.1) years. There were 8 139 women in the normal cardio-metabolic group and 6 058 women in the abnormal cardio-metabolic group. Women with cardio-metabolic disorders in the first trimester had a younger gestational age and higher incidence rates of preterm birth, gestational hypertension, preeclampsia, and gestational diabetes mellitus (all P<0.05). In multivariable Poisson regression, elevated BMI ( RR=1.22, 95% CI 1.15-1.29), elevated FPG ( RR=1.59, 95% CI 1.38-1.82), elevated TG ( RR=1.22, 95% CI 1.13-1.31), and elevated blood pressure ( RR=1.50, 95% CI 1.39-1.63) were independent risk factors for APO, while decreased HDL-C ( RR=0.93, 95% CI 0.70-1.23) was not. Elevated blood pressure ( RR=5.57, 95% CI 4.58-6.78), elevated BMI ( RR=1.71, 95% CI 1.40-2.09), and elevated TG ( RR=1.38, 95% CI 1.10-1.74) had the greatest impact on the risk of developing preeclampsia. Elevated FPG ( RR=1.70, 95% CI 1.45-1.99) had the greatest impact on the risk of gestational diabetes. Conclusions:Elevated blood pressure, BMI, TG and FPG in the first trimester are closely related to APO.

OBJECTIVE To obtain stronger cytotoxic activity of panaxadiol derivatives. METHODS The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle, and then 18 derivatives of cinnamic acid, NO donor and other types of panaxadiol derivatives were synthesized, among them, 12 compounds had not been reported in the literature, and their structures had been confirmed by 1H-NMR, 13C-NMR and mass spectrometry. These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60, liver cancer cell line SMMC-7721, lung cancer cell line A-549, breast cancer cell line MCF-7, and colon cancer cell line SW480. RESULTS These results showed that compounds 6c, 7 as well as 7j exhibited potent inhibitory activities against all five tumor cells, especially the IC50 values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51 μmol·L−1, respectively. It was significantly superior to panaxadiol in cytotoxicity. CONCLUSION These results show that 7 and 7j can be used as promising lead compounds for further research.

AIM: To evaluate the performance of three distinct large language models(LLM), including GPT-3.5, GPT-4, and PaLM2, in responding to queries within the field of ophthalmology, and to compare their performance with three different levels of medical professionals: medical undergraduates, master of medicine, and attending physicians.METHODS: A total of 100 ophthalmic multiple-choice tests, which covered ophthalmic basic knowledge, clinical knowledge, ophthalmic examination and diagnostic methods, and treatment for ocular disease, were conducted on three different kinds of LLM and three different levels of medical professionals(9 undergraduates, 6 postgraduates and 3 attending physicians), respectively. The performance of LLM was comprehensively evaluated from the aspects of mean scores, consistency and confidence of response, and it was compared with human.RESULTS: Notably, each LLM surpassed the average performance of undergraduate medical students(GPT-4:56, GPT-3.5:42, PaLM2:47, undergraduate students:40). Specifically, performance of GPT-3.5 and PaLM2 was slightly lower than those of master's students(51), while GPT-4 exhibited a performance comparable to attending physicians(62). Furthermore, GPT-4 showed significantly higher response consistency and self-confidence compared with GPT-3.5 and PaLM2.CONCLUSION: LLM represented by GPT-4 performs well in the field of ophthalmology, and the LLM model can provide clinical decision-making and teaching aids for clinicians and medical education.

Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.