Objective:To investigate the correlation between multifidus muscle cross-sectional area (CSA), fat infiltration index (FI), and the grading of lumbar facet joint degeneration (FJD).Methods:A retrospective analysis was conducted on the clinical data of 105 patients with lumbar FJD treated at Sichuan Orthopaedic Hospital between January 2015 and December 2020. Patients were divided into three groups according to the Weishaupt grading system: 37 cases with Weishaupt grade 1 (Mild Group), 44 cases with Weishaupt grade 2 (Moderate Group), and 24 cases with Weishaupt grade 3 (Severe Group). Baseline characteristics [sex, age, body mass index (BMI), treatment duration], pathological features at initial diagnosis [segmental distribution, bone mineral density (BMD) T-score, facet joint asymmetry, endplate morphology, Modic classification, Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score], and multifidus muscle MRI findings [multifidus cross-sectional area (CSA) and fat infiltration index (FI)] were compared among the three groups. The correlation between lumbar multifidus CSA, FI, and FJD grade was analyzed. Normally distributed measurement data were expressed as xˉ± s; comparisons among multiple groups were performed by one-way ANOVA, pairwise comparisons were performed by LSD- t tests. Counting data were expressed as case (%) and compared by χ2 test. Spearman correlation analysis was used to analyze the correlation between lumbar multifidus MRI parameters and FJD grade. Results:There were no statistically significant differences among the three FJD groups in sex, age, BMI, treatment duration, segmental distribution, BMD T-score, proportion of facet joint asymmetry, endplate morphology, Modic classification, ODI, or JOA score (all P>0.05). At the L4-5 level, the multifidus CSA on the affected side in the severe group was significantly smaller than in the moderate group and mild group [(6.2±1.2) cm2 vs. (7.0±1.1) cm2 vs. (7.8±1.2) cm2], and the CSA in the moderate group was smaller than in the mild group (all P<0.05). At both the L4-5 and L5-S1 levels, the FI on the affected side in the severe group was significantly greater than in the moderate group and mild group [(0.48±0.12) vs. (0.39±0.15) vs. (0.29±0.10) at L4-5; (0.49±0.12) vs. (0.41±0.10) vs. (0.30±0.13) at L5-S1], and the FI in the moderate group was greater than in the mild group (all P<0.05). Spearman correlation analysis showed that at the L4-5 level, multifidus CSA on the affected side was negatively correlated with FJD grade ( r=-0.41, P=0.004). At the L5-S1 level, FI on the affected side was positively correlated with FJD grade ( r=0.58, P<0.001). Conclusion:The CSA and FI of the multifidus muscle on the affected side in the lumbar spine exhibit significant correlations with the severity of FJD grading. Clinically, early functional exercises can be implemented based on the degree of multifidus muscle degeneration observed in patients.

Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans ; Tumor Microenvironment/drug effects* ; Adenocarcinoma of Lung/drug therapy* ; Lung Neoplasms/pathology* ; Adenocarcinoma/metabolism* ; Animals ; Apoptosis/physiology*

Objective:To investigate the correlation between multifidus muscle cross-sectional area (CSA), fat infiltration index (FI), and the grading of lumbar facet joint degeneration (FJD).Methods:A retrospective analysis was conducted on the clinical data of 105 patients with lumbar FJD treated at Sichuan Orthopaedic Hospital between January 2015 and December 2020. Patients were divided into three groups according to the Weishaupt grading system: 37 cases with Weishaupt grade 1 (Mild Group), 44 cases with Weishaupt grade 2 (Moderate Group), and 24 cases with Weishaupt grade 3 (Severe Group). Baseline characteristics [sex, age, body mass index (BMI), treatment duration], pathological features at initial diagnosis [segmental distribution, bone mineral density (BMD) T-score, facet joint asymmetry, endplate morphology, Modic classification, Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score], and multifidus muscle MRI findings [multifidus cross-sectional area (CSA) and fat infiltration index (FI)] were compared among the three groups. The correlation between lumbar multifidus CSA, FI, and FJD grade was analyzed. Normally distributed measurement data were expressed as xˉ± s; comparisons among multiple groups were performed by one-way ANOVA, pairwise comparisons were performed by LSD- t tests. Counting data were expressed as case (%) and compared by χ2 test. Spearman correlation analysis was used to analyze the correlation between lumbar multifidus MRI parameters and FJD grade. Results:There were no statistically significant differences among the three FJD groups in sex, age, BMI, treatment duration, segmental distribution, BMD T-score, proportion of facet joint asymmetry, endplate morphology, Modic classification, ODI, or JOA score (all P>0.05). At the L4-5 level, the multifidus CSA on the affected side in the severe group was significantly smaller than in the moderate group and mild group [(6.2±1.2) cm2 vs. (7.0±1.1) cm2 vs. (7.8±1.2) cm2], and the CSA in the moderate group was smaller than in the mild group (all P<0.05). At both the L4-5 and L5-S1 levels, the FI on the affected side in the severe group was significantly greater than in the moderate group and mild group [(0.48±0.12) vs. (0.39±0.15) vs. (0.29±0.10) at L4-5; (0.49±0.12) vs. (0.41±0.10) vs. (0.30±0.13) at L5-S1], and the FI in the moderate group was greater than in the mild group (all P<0.05). Spearman correlation analysis showed that at the L4-5 level, multifidus CSA on the affected side was negatively correlated with FJD grade ( r=-0.41, P=0.004). At the L5-S1 level, FI on the affected side was positively correlated with FJD grade ( r=0.58, P<0.001). Conclusion:The CSA and FI of the multifidus muscle on the affected side in the lumbar spine exhibit significant correlations with the severity of FJD grading. Clinically, early functional exercises can be implemented based on the degree of multifidus muscle degeneration observed in patients.

Objective To evaluate the cost-utility of tiotropium/olodaterol in treating Chinese patients with moderate to very severe chronic obstructive pulmonary disease(COPD)and to provide references for selecting more economical inhaled preparations in clinical practice.Methods A four-state lifetime Markov model was established with a 3-month cycle.The health outcomes included life years and quality-adjusted life years.Costs,including direct medical costs,were calculated from the perspective of the Chinese health system.Discontinuation rates were derived from the discontinuation curve using GetData Graph Digitizer.The main output indicator of the model was the incremental cost-utility ratio,which was calculated from the queue simulation results to judge the economy of tiotropium bromide/odataterol.The scenario analysis and sensitivity analyses were carried out to detect the robustness of the base case result.Results Compared with tiotropium bromide,the patient treated with tiotropium bromide/odataterol gained an additional 0.0846 life years,an additional cost of ￥3 201.50,and additional 0.029 6 QALY.The incremental cost-utility ratio was 108 140.11 yuan/QALY,lower than the willingness-to-pay threshold of three times China's per capita GDP in 2021.The costs of tiotropium bromide and tiotropium bromide/odataterol had the greatest impact on the result in the one-way sensitivity analysis.93.8%of the Chinese COPD population was willing to pay for tiotropium bromide/odataterol under the threshold in the probability sensitivity analysis.Conclusion Tiotropium/olodaterol is a cost-effective alternative compared to tiotropium for patients with moderate to very severe COPD in China and the results were robust in the sensitivity analyses.

AIM:To analyze and screen the risk factors for acute kidney injury(AKI)following heart transplantation(HT),and to establish a dynamic no-mograms prediction model to forecast early AKI af-ter HT.METHODS:A retrospective analysis was con-ducted on clinical data from HT recipients at Nan-jing First Hospital from October 2012 to June 2024.Patients were divided into AKI and non-AKI groups based on AKI occurrence within 7 days post-sur-gery,with a 8:2 ratio for training and testing sets.Lasso regression and multivariable logistic regres-sion were used to select influencing factors.A dy-namic nomogram model was visualized using R.In-ternal validation was performed using 1 000 boot-strap samples.Model accuracy and discrimination were evaluated using the area under the receiver operating characteristic curve(AUC-ROC),calibra-tion curves,and the Hosmer-Lemeshow goodness-of-fit test.The nomogram model was compared with the Cleveland score.RESULTS:The results of a multivariable logistic regression indicate that a his-tory of atrial fibrillation(OR=9.647,95％CI=1.961-47.470),vasoactive inotropic score(OR=1.094,95％CI=1.012-1.183),intraoperative transfusion of red blood cells or plasma(OR=10.200,95％CI=1.727-60.238),postoperative central venous pressure(OR=1.548,95％CI=1.186-2.021),and postoperative use of vancomycin(OR=25.082,95％CI=2.122-296.417)are independent risk factors for HT-AKI.The dynamic nomogram model achieved an AUC of 0.842(95％CI:0.676-0.971)in the test set,with a calibration plot showing a slope close to 1 and a Brier score of 0.173.The Hosmer-Lemeshow good-ness-of-fit test(x2=5.658,P=0.685)suggests good predictive performance of the model.Moreover,this model demonstrates superior discriminative ability compared to the Cleveland score.CONCLU-SION:This study identified preoperative,intraoper-ative,and postoperative risk factors influencing the occurrence of HT-AKI.The developed dynamic no-mogram model accurately identifies high-risk indi-viduals for early HT-AKI and is convenient for clini-cal use.

AIM:To analyze and screen the risk factors for acute kidney injury(AKI)following heart transplantation(HT),and to establish a dynamic no-mograms prediction model to forecast early AKI af-ter HT.METHODS:A retrospective analysis was con-ducted on clinical data from HT recipients at Nan-jing First Hospital from October 2012 to June 2024.Patients were divided into AKI and non-AKI groups based on AKI occurrence within 7 days post-sur-gery,with a 8:2 ratio for training and testing sets.Lasso regression and multivariable logistic regres-sion were used to select influencing factors.A dy-namic nomogram model was visualized using R.In-ternal validation was performed using 1 000 boot-strap samples.Model accuracy and discrimination were evaluated using the area under the receiver operating characteristic curve(AUC-ROC),calibra-tion curves,and the Hosmer-Lemeshow goodness-of-fit test.The nomogram model was compared with the Cleveland score.RESULTS:The results of a multivariable logistic regression indicate that a his-tory of atrial fibrillation(OR=9.647,95％CI=1.961-47.470),vasoactive inotropic score(OR=1.094,95％CI=1.012-1.183),intraoperative transfusion of red blood cells or plasma(OR=10.200,95％CI=1.727-60.238),postoperative central venous pressure(OR=1.548,95％CI=1.186-2.021),and postoperative use of vancomycin(OR=25.082,95％CI=2.122-296.417)are independent risk factors for HT-AKI.The dynamic nomogram model achieved an AUC of 0.842(95％CI:0.676-0.971)in the test set,with a calibration plot showing a slope close to 1 and a Brier score of 0.173.The Hosmer-Lemeshow good-ness-of-fit test(x2=5.658,P=0.685)suggests good predictive performance of the model.Moreover,this model demonstrates superior discriminative ability compared to the Cleveland score.CONCLU-SION:This study identified preoperative,intraoper-ative,and postoperative risk factors influencing the occurrence of HT-AKI.The developed dynamic no-mogram model accurately identifies high-risk indi-viduals for early HT-AKI and is convenient for clini-cal use.

Objective:To investigate the correlation between serum lipoprotein (a) [LP(a)] and the severity of white matter hyperintensities (WMHs) in the middle-aged and elderly people in the community.Methods:Consecutive middle-aged and elderly residents residing in the community underwent physical examinations in the Affiliated Jiangning Hospital of Nanjing Medical University from June 2016 to August 2021 were retrospectively collected. Fasting venous blood was collected on the next day of admission to detect the level of Lp(a). During hospitalization, cranial MRI examination was performed and the severity of WMHs was graded using the Fazekas visual scoring method. Ordinal multivariate logistic regression analysis was used to determine independent related factors for the severity of WMHs.Results:A total of 1 752 patients were included in the analysis. There were 969 males (55.31%) and 783 females (44.69%). Their age was 66.18±10.32 years old. There were 1 167 patients (66.61%) in the mild WMHs group, 407 (23.23%) in the moderate WMHs group, and 178 (10.16%) in the severe WMHs group. Ordinal multivariable logistic regression analysis showed that after adjusting for confounding factors, a higher serum Lp(a) level was independently related to the severity of WMHs (with the first quartile as a reference, the third quartile: odds ratio 1.441, 95% confidence interval 1.050-1.976, P=0.023; the fourth quartile: odds ratio 1.717, 95% confidence interval 1.252-2.354, P=0.001). Conclusion:Serum Lp(a) is independently correlated with the severity of WMHs.

ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor- at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-B (NF-B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-B signaling pathway and inflammatory responses.

Objective:To explore the effects of aloe vera extra (AVE) on lipopolysaccharide (LPS)-induced inflammatory response of human periodontal ligament cells(hPDLCs).Methods:hPDLCs were induced with LPS at 1 μg/ml for the simulation of periodontitis model(model group) and then treated by AVE at 0.05,0.1,0.2 mg/ml respectively(AVE group).Cell viability was examined by MTT assay.The level of interleukin-6(IL-6) from cell culture medium was measured by ELISA.The expression of Toll like receptor 4(TLR4) protein was detected by immunocytochemistry staining and the transfer of nuclear factor-kappa B p65 (NF-κB-p65) was observed by immunofluorescence staining.Results:There was no significant difference of the cell viabilities among the groups.IL-6 in culture medium,the expression of TLR4 protein and the transfer of NF-κB-p65 into the nucleus were increased in model group.AVE at 0.05-0.2 mg/ml inhibited the secretion of IL-6 in the cell culture supernatant down-regulated the TLR4 expression,attenuated the transfer of NF-κB-p65 into the nucleus in a concentration-dependent manner.Conclusion:Aloe vera extract can inhibit the inflammation response of hPDLCs induced by LPS through TLR4/ NF-κB-p65 signaling pathway.

Objective To explore the anti-inflammatory and antipruritic effects of Chushizhiyang ointment in a mouse model. Methods A total of 40 male 8-week-old BALB/c mice were included in this study, and randomly and equally divided into 4 groups. A mouse model of atopic dermatitis (AD)was established in three groups of mice by repeated application of 2,4-dinitroflurobenzene (DNFB)to shaved abdominal skin for sensitization and to shaved dorsal skin for stimulation. After establishment of the AD model, the three groups were topically treated with sodium chloride physiological solution (model group), hydrocortisone cream (hydrocortisone group)and Chushizhiyang ointment (Chushizhiyang group)respectively for 14 consecutive days. The remaining group receiving no sensitization or treatment served as the normal control group. All the mice were sacrificed 12 hours after the final treatment, and the dorsal skin of mice was resected followed by the determination of skin thickness and weight as well as hematoxylin-eosin(HE)staining and toluidine blue staining for the counting of leukocytes and mast cells respectively. Moreover, enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of interferon-gamma(IFN-γ), tumor necrosis factor alpha(TNF-α), interleukin 4(IL-4)and IL-5 in dorsal skin lesions. In addition, a local skin itching model was induced by histamine phosphate in Hartley guinea pigs, which was used to explore the effect of Chushizhiyang ointment on itch thresholds. Results Compared with the model group, both the Chushizhiyang group and hydrocortisone group showed reduced thickness and weight of dorsal skin in mice (all P < 0.01), numbers of infiltrating lymphocytes and mast cells (all P < 0.01)and levels of IFN-γ, TNF-α, IL-4 and IL-5 in skin lesions (P < 0.05 or 0.01)on day 15 after the start of treatment. The thickness and weight of dorsal skin in mice were significantly decreased in the hydrocortisone group (P <0.01), but experienced no significant changes in the Chushizhiyang group compared with the normal control group. Additionally, Chushizhiyang ointment could significantly increase itch thresholds in guinea pigs induced by histamine phosphate(P < 0.01). Conclusions Chushizhiyang ointment can significantly inhibit DNFB-induced AD in mice, likely by restoring the balance between Th1 and Th2 type cytokines. Moreover, Chushizhiyang ointment could markedly relieve itching induced by histamine phosphate in guinea pigs.