Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide. Among its histological subtypes, non-small cell lung cancer (NSCLC) accounts for the majority of cases, representing the predominant pathological type. Notably, in the elderly population, NSCLC continues to be a major contributor to cancer-related deaths. With the global ageing population, immunosenescence has emerged as a key factor influencing the occurrence, progression, and the efficacy of immunotherapy of NSCLC. Immunosenescence refers to the age-related decline in immune system function, which manifests as alterations in both the quantity and functionality of immune cells. These include thymic involution, T cell exhaustion, epigenetic modifications, weakened immune responses, and a chronic low-grade inflammatory state. This review comprehensively analyzes the role of immunosenescence in elderly patients with advanced NSCLC and proposes potential therapeutic strategies to intervene in the immunosenescence process. By targeting immunosenescence, these strategies aim to inhibit the progression of NSCLC and improve the effectiveness of immunotherapy.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Immunotherapy ; Lung Neoplasms/genetics* ; Immunosenescence ; Aged

Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.

Objective:To investigate the diagnostic performance of different thyroid imaging reporting and data systems (TI-RADS) in the diagnosis of medullary thyroid carcinoma (MTC) .Methods:A total of 160 thyroid nodules diagnosed as MTC by postoperative pathology from Aug. 2011 to Aug. 2022 at the First Affiliated Hospital of Zhengzhou University were included. Additionally, 160 papillary thyroid carcinomas (PTC) and 160 benign nodules were randomly selected as controls during the same period. Differences in gender, age, nodule diameter and various ultrasound features were observed. The nodules were classified according to American College of Radiology (ACR) TI-RADS, artificial intelligence (AI) TI-RADS and Chinese (C TI-RADS). Then, receiver operating characteristic curve (ROC) were plotted to calculate the diagnostic value. The Kendall concordance coefficient was used to evaluate the interobserver consistency of each TI-RADS system.Results:There was no statistically significant difference in gender among the three groups ( χ2=1.17, P=0.558). However, significant differences were observed in age and nodule diameter ( F=12.08,40.12, P<0.001 for both). The area under ROC (AUC) for diagnosing MTC and benign nodules using ACR, AI, and C-TIRADS were 0.762, 0.773, and 0.761, respectively, with no statistically significant differences ( Z=1.33, 0.01, 0.87, P=0.183, 0.994, 0.386). However, the sensitivity of C TI-RADS (87.5%) was lower than that of ACR and AI TI-RADS (both 95.0%) ( P=0.018). After combining the biopsy threshold, the false negative rate of C-TIRADS was lower than that of ACR (30.6% vs. 41.3%) ( P=0.048) and AI TIRADS (30.6% vs. 43.1%) ( P=0.020). The inter-observer diagnostic consistency of C-TIRADS was superior to ACR (0.884 vs. 0.819, P<0.001) and AI TIRADS (0.884 vs. 0.839) ( P<0.001) . Conclusions:AI and ACR TI-RADS have higher sensitivity in diagnosing MTC, while C TI-RADS has a lower puncture missed diagnosis rate. AI has similar diagnostic performance to ACR TI-RADS and can replace ACR TI-RADS.

Objective:To prepare recombinant protein of group 36 allergen of Dermatophagoides farinae(Der f 36),to deter-mine its immunogenicity and bioinformatics analysis was performed.Methods:Nucleic acid sequence coding for Der f 36 was obtained and artificially synthesized,pET-28a(+)was inserted to construct pET-28a(+)-Der f 36 plasmid and transformed into BL21(DE3)receptor cells.After expressed and purified in BL21(DE3),recombinant allergen rDer f 36 was obtained,recombinant protein rDer f 36 was identified by SDS-PAGE and Western blot.Serum IgE binding rates of rDer f 36 was determined by IgE-ELISA.Cross-reactivity between rDer f 36 and rDer p 36 was detected by IgE-ELISA inhibition assay.HNEpC cells were cultured with rDer f 36 for 24 h and cytokines were detected.Bioinformatics softwares were used to analyze physicochemical properties and structures of Der f 36 and Der p 36.Results:Coding gene for Der f 36 was obtained with a total length of 690 bp,whose molecular weight was 25.6 kD;serum IgE binding rate of rDer f 36 was 42.1%by IgE-ELISA;IgE-ELISA inhibition assay showed that rDer p 36 had 40%(8/20)inhibition rate(>50%)for rDer f 36,with an average inhibition rate of 52.98%.Compared with control group,HNEpC cells cultured with rDer f 36 showed that IL-6,IL-8,IL-33,IL-25 and TSLP expressions had increased;bioinformatics analyses show that sequence consistency of Der f 36 and Der p 36 was 77.63%,with similar physicochemical properties.Secondary structure analysis showed that both of them contained α helix,β-turn and random coils,and content of random coils was the highest;structure of C2 domains was also highly overlapping(RMSD=0.046).Conclusion:Recombinant allergen rDer f 36 is successfully prepared with good immunogenicity,laying foundation for diagnosis and treatment of dust mite allergen single component.High similarity in physical and chemical properties,secondary structure,and tertiary structure between Der f 36 and Der p 36 determines their cross reactivity.

Objective:To prepare recombinant protein of group 27 allergen of Dermatophagoides farinae(Der f 27),and to determine its immunoactivity.Methods:pET-28a(+)-Der f 27 plasmid was constructed and inserted into E.coli BL21(DE3)cells.After being expressed and purified,recombinant allergen rDer f 27 was obtained.IgE binding rates of rDer f 27 with sera from patients with allergic rhinitis induced by Dermatophagoides farinae was determined by ELISA and Western blot.PBMC from patients with allergic rhinitis and BESA-2B cells were cultured with rDer f 27 for 24 h,respectively,and cytokine expression was measured.Bioinformatics softwares were used to analyze physicochemical properties and structures of Der f 27.Results:pET-28a(+)-Der f 27 plasmids were prepared successfully and transformed into BL21(DE3)cells.After expressed and purified with PTG,SDS-PAGE and Western blot identified a band about 48 kD.IgE binding rates of rDer f 27 were 39.5%and 45.5%with sera from patients with allergic rhinitis allergic to Dermatophagoides farinae by IgE-ELISA and IgE-Western blot,respectively.Compared with control group,IL-6 and IL-8 expressions were increased in PBMC from patients with allergic rhinitis being cultured with rDer f 27(P<0.05);expressions of IL-10 and TGF-β were decreased in BESA-2B cells being cultured with rDer f 27,while IL-17A and IL-23A expressions were increased.Bioinformatics analysis showed that Der f 27 belong to serine protease inhibitor family and had universal structure and func-tion of this family.Secondary structure of Der f 27 was mainly composed of α-helix(42.62%)and random coil(35.60%).Conclusion:Recombinant allergen rDer f 27 has been prepared successfully with good immunoreactivity and immunogenicity,becoming one of important allergens of allergic rhinitis.

The present study was aimed to produce the recombinant protein of Tyrophagus putrescentiae allergen component 32 (Tyr p 32) and to identify its immunoreactivity. The cDNA encoding Tyr p 32 was amplified from total RNA of T. putrescentiae and inserted into pET-28a (+) vector. The constructed plasmid pET-28a (+)-Tyr p 32 was transformed into BL21 (DE3) receptor cells. After being induced with IPTG, the recombinant protein was purified with Ni column, and then identified on SDS-PAGE and Western blotting. Serum of children with allergic asthma and(or) rhinitis was collected, IgE-ELISA and IgE-Western blotting were used to detect the binding rate of rTyr p 32 to human T.putrescentiae-positive serum. After human bronchial epithelial cells BEAS-2B being cultured with rTyr p 32, the expression levels of IL-6 and IL-8 cytokines was detected by ELISA and qRT-PCR, t-test was used for pairwise comparison between groups. The results showed that the cDNA length of Tyr p 32 was 885 bp. The sequence identity between Tyr p 32 and Der p 32, Der f 32 was 70.21% and 68.03%, respectively. According to SDS-PAGE and Western blotting, the molecular weight of rTyr p 32 was about 35 000 Da, which was consistent with the theoretical value. IgE-ELISA results showed that the positive rate of rTyr p 32 was 41.38% (12/29) against T. putrescentiae-positive serum. When BEAS-2B cells were cultured with rTyr p 32, the expression of IL-6 and IL-8 increased in the cell supernatant in a dose-dependent manner ( t=-29.10, P=0.001 2; t=-33.69, P=0.000 9), which also significantly increased the mRNA expression levels of IL-6 and IL-8 ( t=-9.15, P=0.011 7; t=-17.16, P=0.003 4). In conclusion, the recombinant protein rTyr p 32 was successfully prepared, which provides raw materials for component diagnosis and specific immunotherapy of allergic diseases.

The present study was aimed to produce the recombinant protein of Tyrophagus putrescentiae allergen component 32 (Tyr p 32) and to identify its immunoreactivity. The cDNA encoding Tyr p 32 was amplified from total RNA of T. putrescentiae and inserted into pET-28a (+) vector. The constructed plasmid pET-28a (+)-Tyr p 32 was transformed into BL21 (DE3) receptor cells. After being induced with IPTG, the recombinant protein was purified with Ni column, and then identified on SDS-PAGE and Western blotting. Serum of children with allergic asthma and(or) rhinitis was collected, IgE-ELISA and IgE-Western blotting were used to detect the binding rate of rTyr p 32 to human T.putrescentiae-positive serum. After human bronchial epithelial cells BEAS-2B being cultured with rTyr p 32, the expression levels of IL-6 and IL-8 cytokines was detected by ELISA and qRT-PCR, t-test was used for pairwise comparison between groups. The results showed that the cDNA length of Tyr p 32 was 885 bp. The sequence identity between Tyr p 32 and Der p 32, Der f 32 was 70.21% and 68.03%, respectively. According to SDS-PAGE and Western blotting, the molecular weight of rTyr p 32 was about 35 000 Da, which was consistent with the theoretical value. IgE-ELISA results showed that the positive rate of rTyr p 32 was 41.38% (12/29) against T. putrescentiae-positive serum. When BEAS-2B cells were cultured with rTyr p 32, the expression of IL-6 and IL-8 increased in the cell supernatant in a dose-dependent manner ( t=-29.10, P=0.001 2; t=-33.69, P=0.000 9), which also significantly increased the mRNA expression levels of IL-6 and IL-8 ( t=-9.15, P=0.011 7; t=-17.16, P=0.003 4). In conclusion, the recombinant protein rTyr p 32 was successfully prepared, which provides raw materials for component diagnosis and specific immunotherapy of allergic diseases.

Objective The study was to investigate the activation of tumor necrosis factor α (TNF-α) mRNA transcription and protein expression in peripheral blood and activation of signal path PI3K/AKT in patients with chronic heart failure. Methods From February 2015 to April 2018, 244 patients with heart failure in the cardiovascular department of our hospital were selected as heart failure group, while 244 healthy cases were enrolled as the control group at the same time. The peripheral blood samples of two groups were collected. We detected the transcription and protein expression of TNF-α mRNA and the activation of PI3K, AKT in peripheral blood. The left ventricular ejection fraction (LVEF) were measured in two groups. The correlations between influencing factors and LVEF were analyzed. Results The levels of PI3K, AKT in the heart failure group were higher than those in the control group. The differences were statistically significant respectively (P < 0.05). The mRNA relative content and protein content of TNF-α in peripheral blood mononuclear cells of heart failure group were higher compared with those of control group (P < 0.05). The LVEF of heart failure group was significantly lower than that of the control group (34.50 ± 6.33) ％ versus (55.60 ± 2.49) ％, P < 0.001). Among 244 patients with heart failure, Spearman correlation analysis showed that there were significant positive correlations between TNF-a mRNA and protein expression levels and the levels of PI3K, AKT respectively (P < 0.05). Multiple factors unconditional Logistic regression analysis showed that the TNF-α mRNA, protein expression and PI3K, AKT levels in peripheral blood were independent risk factors for LVEF (P < 0.05). Conclusion The expression levels of PI3K, AKT and TNF-α are all significantly increased in chronic heart failure patients, which could participate in the occurrence and development of heart failure.

Objective: To observe the difference in anti-inflammatory effect between living rhino horn and rhino horn by the method of comparative research to provide the experimental basis for the replacement of rhino horn by living rhino horn.Methods: The anti-inflammatory effects of living rhino horn and rhino horn were studied by the methods of paw edema in rats, cotton ball granuloma in mice, auricle swelling and peritoneal dye penetration.Results: Compared with that in the model control group, the foot metatarsus swelling degree at all time points in high (440 mg·kg-1) dose group and middle (220 mg·kg-1) dose group of living rhino horn and three doses groups of rhino horn showed statistical differences (P＜0.05 or P＜0.01).The high dose group (700 mg·kg-1) and middle dose group (350 mg·kg-1) of living rhino horn and rhino horn could significantly reduce the weight of cotton ball granuloma in mice (P＜0.05).Three doses groups (700, 350 and 175 mg·kg-1) of living rhino horn and rhino horn could significantly reduce auricle swelling in mice induced by xylene (P＜0.05 or P＜0.01).The absorbance of Evansan in the abdominal cavity in the middle dose group (350 mg·kg-1) of rhino horn and the high dose group (700 mg·kg-1) and middle (350 mg·kg-1) dose group of living rhino horn was significantly reduced (P＜0.05 or P＜0.01).There was no significant difference in the anti-inflammatory effect between living rhino horn and rhino horn at the same dose.Conclusion: Living rhino horn and rhino horn have a certain anti-inflammatory effect.The anti-inflammatory effect of living rhino horn is similar to those of the rhino horn, and living rhino horn can be used as a substitute of rhino horn.