Chemotherapy based on cisplatin or its combination therapy is a common cancer treatment method. However， the non-specific side effects of cisplatin， poor pharmacokinetic properties of small molecule drugs， and susceptibility to drug resistance greatly limit the clinical application of cisplatin as first-line anti-tumor drug. With the development of nanocarrier technology， liposomes have become an ideal carrier for delivering cisplatin drugs due to their excellent properties of targeting， reducing toxicity， and enhancing efficacy. This paper reviews the status of cisplatin liposome both domestically and internationally which have entered clinical trials， including L-NDDP，SPI-077®， Lipoplatin®，LiPlaCis，SLIT and ILC， etc. Currently， only Lipoplatin® and ILC are showing good potential in cancer therapy. Although cisplatin liposome has made some progress in reducing systemic toxicity and improving treatment efficiency in clinical research， there is still potential for further improvement in tumor targeting and reducing side effects. In the future， more low-toxicity and efficient cisplatin liposomes can be developed through formulation technologies such as co-delivery liposome， stimuli-responsive liposome and targeting liposome.

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 investigate the relationship between serum adipokine expression and insulin resistance in individuals with different degrees of glucose intolerance, and to assess the value of these adipokines in predicting the risk of progression in prediabetes. Methods A total of 114 participants with oral glucose tolerance test were enrolled and divided into three groups based on diagnostic and classification criteria for diabetes: normal glucose tolerance (NGT, n=32), impaired glucose tolerance (IGT, n=46), and type 2 diabetes mellitus (T2DM, n=36). Serum levels of adiponectin (APN), leptin (LEP) and preadipocyte factor-1 (Pref-1) as well as homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for pancreatic β-cell function (HOMA-β) were compared among the three groups. Pearson correlation analysis was conducted to explore the correlations of serum APN, LEP and Pref-1 levels with HOMA-IR and HOMA-β. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of serum APN, LEP and Pref-1 levels for the progression of prediabetes. Results Serum APN levels were significantly lower in the T2DM and IGT groups compared to the NGT group, with further significant reduction observed in the T2DM group compared to the IGT group (P < 0.05); conversely, serum LEP, Pref-1, fasting plasma glucose (FPG), 2-hour postprandial glucose (2 hPG), fasting insulin (FINS), glycated hemoglobin (HbA1c), triglycerides (TG) and C-reactive protein (CRP) levels were significantly higher in the T2DM and IGT groups than in the NGT group, with additional significant increases observed in the T2DM group compared to the IGT group (P < 0.05). HOMA-IR was significantly lower in both the T2DM and IGT groups than in the NGT group, with a further significant decrease in the T2DM group compared to the IGT group (P < 0.05). HOMA-β was significantly higher in both the T2DM and IGT groups compared to the NGT group, with a further significant increase in the T2DM group versus the IGT group (P < 0.05). Serum APN level was positively correlated with HOMA-IR (r=0.547, P < 0.05) and negatively correlated with HOMA-β (r=-0.506, P < 0.05); serum LEP and Pref-1 levels were negatively correlated with HOMA-IR (r=-0.325, -0.459, P < 0.05) and positively correlated with HOMA-β (r=0.317, 0.428, P < 0.05). ROC curve analysis revealed optimal cut-off values for serum APN, LEP and Pref-1 levels in predicting the progression of prediabetes were 15.98 mg/L, 4.23 mg/L and 18.85 μg/L, respectively. The combination of these three biomarkers showed a sensitivity of 80.43%, a specificity of 96.87%, and an area under the curve (AUC) of 0.925. Conclusion Serum levels of APN, LEP and Pref-1 abnormally change in patients with impaired glucose tolerance and are associated with insulin resistance. These adipokines can serve as sensitive indicators for predicting the progression of prediabetes, with higher predictive value when used in combination.

AIM:To explore the effect of polyphenolic compound 3,5-dihydroxy-4-methoxybenzyl alcohol(DHMBA)on hypoxia/reoxygenation(H/R)injury of human umbilical vein endothelial cells(EA.hy926 cells)and its po-tential mechanisms.METHODS:To construct an H/R model,the EA.hy926 cells were cultured in an acidic hypoxia buffer while in an anaerobic workstation.The cells were divided into control,H/R,H/R+different doses of DHMBA,H/R+edaravone(antioxidant)and H/R+reactive oxygen species(ROS)inducer oligomycin A+DHMBA groups.Cell viability was measured by CCK-8 assay,and tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in cells were mea-sured by ELISA.Phosphorylation of endothelial nitric oxide synthase(eNOS)and nuclear factor-κB(NF-κB)p65 were measured by Western blot.Intracellular NO levels were determined by laser confocal microscopy.Glutathione(GSH)/glu-tathione disulfide(GSSG)oxidation balance was determined by the dinitrobenzoic acid chromogenic method.Intracellular ROS levels were measured by flow cytometry.Lactate dehydrogenase(LDH)leakage was determined using nitro blue tet-razolium staining.Scratch assays were performed to assess cell migration.RESULTS:DHMBA exhibited no significant cytotoxicity between 125 and 1 000 μmol/L.In H/R-injured human umbilical vein endothelial cells,DHMBA improved cell survival,inhibited phosphorylation of NF-κB p65,reduced the content of TNF-α and IL-6,and increased phosphory-lation of eNOS and NO levels.DHMBA also suppressed ROS overload and restored the ratio between GSH and oxidized GSH,decreased in LDH leakage and increased cell migration in H/R-injured human umbilical vein endothelial cells.CONCLUSION:DHMBA can alleviate H/R-induced oxidative stress,inflammation,cellular damage,and dysfunction,which are associated with the ability of DHMBA to inhibit ROS production in human umbilical vein endothelial cells.

AIM:To explore the molecular mecha-nism of Fuyangjing gel in the treatment of chronic eczema rats model based on janus protein kinase 1(JAK1)/signal transducer and activator of transcrip-tion 5(STAT5)signaling pathway.METHODS:Thirty-six SPF Wistar rats were randomly divided into nor-mal group,model group,Qingpeng ointment group,Fuyangjing gel low,medium and high dose groups.Except the normal group,the other groups of rats were treated with 2,4-dinitrochlorophenone solution to induce chronic eczema-like lesions on the back.After 3 weeks of modeling,Qingpeng ointment group and Fuyangjing gel low,medium and high dose groups were respectively treated with corresponding drugs.The model group was smeared with blank gel matrix once a day for 2 weeks,while the normal group was not treated.The severity and pathological changes of back le-sions in chronic eczema rats were observed.The ex-pression of phosphorylated protein tyrosine kinase 1(p-JAK1)and phosphorylated signal transduction and transcriptional activator 5(p-STAT5)in rat dor-sal skin was detected by Western blot.Detection of thymic stromallymphopietin(TSLP),JAK1,STAT5,in-terleukin-10(IL-10)and IL-17 mRNA expression lev-els in rat back skin by qRT-PCR;The levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in serum of rats were deter-mined by enzyme-linked immunosorbent assay(ELI-SA).RESULTS:Compared with normal group,the se-rum levels of IL-4,IL-6,IL-13 and IL-17 in model group were significantly increased,while IL-10 lev-els were significantly decreased(P＜0.05).The ex-pression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significantly increased,while IL-10 mRNA levels were significantly decreased(P＜0.05).Compared with model group,serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng ointment group and Fuy-angjing gel low,medium and high dose groups were significantly decreased,while IL-10 levels were significantly increased(P＜0.05).The expres-sion levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significantly decreased,while the mRNA levels of IL-10 were significantly increased(P＜0.05).The serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng oint-ment group were decreased,while IL-10 levels were increased(P＜0.05).The expression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were decreased,while the mRNA levels of IL-10 were increased(P＜0.05).Com-pared with Qingpeng ointment group,there were no significant differences in serum levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in Fuyangjing gel high-dose group(P＞0.05).There were no significant differenc-es in the expression levels of p-JAK1,p-STAT5 pro-tein and TSLP,JAK1,STAT5,IL-10 and IL-17 mRNA in back lesions(P＞0.05).CONCLUSION:Fuyangjing gel may play a role in the treatment of chronic eczema by regulating the expression of JAK1/STAT5 signal-ing pathway related inflammatory factors,proteins and genes.

Objective To observe splenic T cell apoptosis and XIAP-associated factor 1(XAF1),FAS,and tumor necrosis factor(TNF)-α protein expression levels in rats with acute lung injury(ALI),and to determine their roles in the protective effect of Yifei Jianpi formula.Methods Sixty male specific pathogen-free SD rats were divided randomly into blank,model,positive control,and high-,medium-,and low-dose Yifei Jianpi formula groups.Rats in the positive control group were given 0.5 g/kg dexamethasone by gavage,and rats in the high-,medium-,and low-dose Yifei Jianpi formula groups were given 12,6,and 3 g/kg Yifei Jianpi formula by gavage,respectively.Rats in the model and blank groups were given equal amounts of saline by gavage.All medications were administered once a day for 14 days.Lung function testing was carried out in all rats.We observed the imaging characteristics of the lungs and changes in the organ index and lung tissue wet/dry weight(W/D)in each group,and detected the pathological changes in lung tissues by hematoxylin-eosin staining.Splenic T-cell subpopulations(CD4+/CD8+)and apoptosis of splenic T-cells were detected by flow cytometry and XAF1,FAS,and TNF-α protein expression levels in the spleen were detected by Western Blot.Results Rats in the model group showed reduced lung function,decreased spleen and thymus organ indexes,and significantly higher W/D of lung tissue(P＜0.01).In addition,they had inflammatory exudation and alveolar rupture in the lung tissue,accompanied by thickening of the lung texture and large areas of ground-glass shadows,with a significant decrease in T-cell subsets(CD4+/CD8+)and significant increases in XAF1,FAS,and TNF-α proteins,and in the rate of T-cell apoptosis(P＜0.01).Yifei Jianpi formula significantly reduced the W/D spleen of rat lung tissues,significantly increased the thymus organ index(P＜0.05,P＜0.01)and the T-cell subpopulation(CD4+/CD8+),and significantly decreased the protein expression levels of XAF1,FAS,and TNF-α,and the T-cell apoptosis rate(P＜0.05,P＜0.01).Conclusions ALI induced up-regulation of XAF1,FAS,and TNF-α protein expression and T-cell apoptosis in the spleen of rats,and Yifei Jianpi formula may protect against ALI by down-regulating these factors.

A virus was successfully isolated from a sick cat exhibiting clinical signs such as oral mu-cosal ulceration,nasal mucosal redness,and increased nasal secretions utilizing F81 cells.Through a comprehensive analysis as such PCR amplication,sequencing,morphology,serology,and animal re-gression tests,the virus was identified as a feline calicivirus and named FCV-BJ,an inactivated vac-cine was developed from this isolated strain its safety and efficacy were assessed.The results re-vealed that the isolated FCV-BJ strain exhibited characteristic serological and morphological fea-tures consistent with caliciviruses.Furthermore,inoculation of cats with the FCV-BJ demonstrated the strain is highly virulent and the cats manifested the clinical signs of feline calicivirus infection.For the vaccination trial,domestic cats were immunized with inactivated fifth-generation virus cell culture at varying dilutions,followed by a booster immunization after 21 days.Fourteen days after the challenge with the virus,cats immunized with 107.0 TCID50/mL or higher remained largely healthy,while all cats in the control group developed clinical signs of FCV.These findings suggest that the inactivated vaccine derived from the FCV-BJ isolate exhibits strong immunogenicity and protective efficacy at a minimum immunization dose of 107.0 TCID50/mL.This strain holds promise as a candidate for vaccine production,providing a valuable reference and foundation for future re-search and development of feline calicivirus vaccines.

Objective:To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure.Methods:This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded.Results:CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions:CCM has better short-term safety and efficacy in patients with heart failure.

Objective To analyze the disease burden and change trend of breast cancer mortality among Chinese women from 2013 to 2021.Methods The indicators of breast cancer-related mortality (MR),age-standardized mortality rate (ASMR),deaths,and urban-rural deaths in the Chinese Cause of Death Surveil-lance Dataset from 2013 to 2021 were collected and collated,and the trend changes of MR,ASMR,and years lost in life of premature death (YLL) were analyzed,annual percentage change (APC) was used for trend a-nalysis,and Fisher substitution test was used to compare APC in different regions.Results From 2013 to 2021,a total of 88112 cases of breast cancer died,with an average annual MR of 7.56/100000 and an ASMR of 6.34/100000.From 2013 to 2021,the MR rate of breast cancer (APC=2.12%,t=5.414,P<0.001),MR in rural areas (APC=2.84%,t=7.581,P<0.001),and YLL in rural areas (APC=1.61%,t=3.588,P=0.009) showed an upward trend in China.MR at 40-<45 years old showed a downward trend (APC=-2.76%,t=-4.689,P=0.002),and at 70-<75 years old (APC=1.41%,t=2.494,P=0.041),75-<80 years old (APC=3.05%,t=3.690,P=0.008),and 80-<85 years old (APC=1.82%,t=2.909,P=0.023).There was a statistically significant difference in APC between MR and ASMR in urban and rural areas (P<0.001).There was no significant difference in the trend of other indicators (P>0.05).Conclusion From 2013 to 2021,the disease burden of breast cancer mortality in Chinese women showed an upward trend,and the comprehensive prevention and treatment of breast cancer should be strengthened to reduce the risk of breast cancer death.