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 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 To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.

BACKGROUND:Among the pathogenic factors of cervical spondylosis,herniation of the intervertebral disc,dislocation of the facet joint and the stenosis of the intervertebral foramen are important factors leading to symptoms in patients.Moreover,inappropriate manipulation may aggravate the possibility of cervical disc rupture,leading to exacerbation of symptoms in patients. OBJECTIVE:To compare the effect between sagittal cervical manipulation and traditional cervical rotation manipulation on the area of the intervertebral disc,facet joint and intervertebral foramen at the operative segment by the finite element analysis. METHODS:The neck CT data of a male volunteer with a normal neck were selected and imported into Mimics 17.0 three-dimensional reconstruction software.Geo-magic Studio 12.0,Solidworks 2017 and Ansys Workbench 17.0 software were used for the construction of the finite element model of cervical vertebrae(C3-6)including intervertebral disc and articular cartilage.The lower end plate of the C5 vertebral body was fixed.A uniformly distributed vertical downward 50 N load was applied on the upper surface of the upper vertebral body(C3).The stress,deformation and deformation direction of the C4-5 intervertebral disc,joint capsule stress,the displacement of facet joints and the area of bilateral intervertebral foramen were compared between sagittal cervical manipulation and traditional rotation reduction. RESULTS AND CONCLUSION:(1)When using the rotation technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 8.06 MPa;the total deformation was 1.05 mm,and the fiber ring expanded to the left and outside.When using the sagittal tip lifting technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 2.60 MPa;the total deformation was 0.90 mm,and the fiber ring expanded to the left and back.Compared with the rotation technique,the pressure of the cervical manipulation technique on the disc was less(about 32.3%of the rotation technique),and the deformation degree of the disc was also light(about 85.7%of the rotation technique).(2)When the rotation technique was used,the maximum stresses of the left and right articular capsule ligaments were 0.37 MPa and 1.69 MPa,respectively.The overall displacement of the facet joint was 2.21 mm.The area of the right intervertebral foramen decreased by about 3.8%and the area of the left intervertebral foramen increased by about 0.9%.When the sagittal end lifting manipulation was performed,the maximum stresses of the left and right articular capsule ligaments were 0.27 MPa and 1.70 MPa,respectively;the overall displacement of the facet joint was 1.63 mm;the area of the right intervertebral foramen increased by about 2.6%,and the area of the left intervertebral foramen decreased by about 0.9%.Compared with rotation manipulation,sagittal end lifting manipulation had fewer changes in the displacement of facet joint,joint capsule stress and intervertebral foramen area,so it was safer to operate.(3)In conclusion,compared with cervical rotation manipulation,sagittal end lifting manipulation has fewer changes in facet joint displacement,intervertebral disc stress/deformation degree,joint capsule stress,and foraminal area.In clinical practice,more appropriate manipulation should be selected based on biomechanical results after an accurate assessment of patients'conditions.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.