BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To investigate the association between the local renin-angiotensin system (RAS) in human follicular fluid (hFF) and age, ovarian function, in vitro fertilization (IVF) laboratory outcome. Methods:A non-intervention observational study was designed. hFF and medical case history without personal identity of patients who received IVF simply because of male factor infertility in Reproductive Medicine Center, the First Affiliated Hospital of Soochow University during January 2021 and February 2022 were collected. The renin, angiotensin converting enzyme (ACE), ACE2, angiotensin (Ang)Ⅱ and Ang 1-7 levels were detected by enzyme-linked immunosorbent assay kit. The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF laboratory outcome.Results:1) A total of 139 samples of analysable hFF were obtained. 2) There was a linear negative correlation between age and renin (Pearson's r=-0.313 3, P<0.001), angiotensin converting enzyme (ACE; Pearson's r=-0.183 6, P=0.031), angiotensinⅡ (AngⅡ; Pearson's r=-0.218 6, P=0.010), ACE/ACE2 (Pearson's r=-0.319 2, P<0.001), AngⅡ/Ang1-7 (Pearson's r=-0.224 3, P=0.008), while the linear relationship with ACE2 and Ang1-7 was not significant (all P>0.05). 3) Basal follicle-stimulating hormone was positively correlated with age ( β=0.636, P<0.001), ACE2 ( β=0.267, P=0.026) and AngⅡ ( β=0.268, P=0.001), while negatively correlated with ACE ( β=-0.320, P<0.001) and Ang1-7 ( β=-0.217, P=0.014). Basal luteinizing hormone was positively correlated with AngⅡ ( β=0.330, P=0.003), while negative correlated with Ang1-7 ( β=-0.395, P=0.002). Antral follicle count was positively correlated with Ang1-7 ( β=0.153, P=0.049), while negatively correlated with age ( β=-0.869, P<0.001) and ACE2 ( β=-0.082, P=0.004). Basal anti-Müllerian hormone was only negatively correlated with age ( β=-0.349, P<0.001). There was no correlation between RAS and basal estradiol, progesterone, prolactin, testosterone (all P>0.05). 4) Oocyte retrieval count was positively correlated with renin ( β=0.146, P=0.014), AngⅡ ( β=0.113, P=0.034) and Ang1-7 ( β=0.185, P=0.002), while negatively correlated with age ( β=-0.717, P<0.001); MⅡ oocyte maturation rate was positively correlated with AngⅡ ( β=0.207, P=0.019) and Ang1-7 ( β=0.217, P=0.026), while negatively correlated with age ( β=-0.518, P<0.001). There was no correlation between RAS and the rates of two pronuclei embryos, transplantable embryos, high-quality embryos (all P>0.05). Conclusion:The local RAS in ovarian follicles is affected by age and correlated with ovarian function and IVF laboratory outcome.

Objective:To investigate the association between the local renin-angiotensin system (RAS) in human follicular fluid (hFF) and age, ovarian function, in vitro fertilization (IVF) laboratory outcome. Methods:A non-intervention observational study was designed. hFF and medical case history without personal identity of patients who received IVF simply because of male factor infertility in Reproductive Medicine Center, the First Affiliated Hospital of Soochow University during January 2021 and February 2022 were collected. The renin, angiotensin converting enzyme (ACE), ACE2, angiotensin (Ang)Ⅱ and Ang 1-7 levels were detected by enzyme-linked immunosorbent assay kit. The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF laboratory outcome.Results:1) A total of 139 samples of analysable hFF were obtained. 2) There was a linear negative correlation between age and renin (Pearson's r=-0.313 3, P<0.001), angiotensin converting enzyme (ACE; Pearson's r=-0.183 6, P=0.031), angiotensinⅡ (AngⅡ; Pearson's r=-0.218 6, P=0.010), ACE/ACE2 (Pearson's r=-0.319 2, P<0.001), AngⅡ/Ang1-7 (Pearson's r=-0.224 3, P=0.008), while the linear relationship with ACE2 and Ang1-7 was not significant (all P>0.05). 3) Basal follicle-stimulating hormone was positively correlated with age ( β=0.636, P<0.001), ACE2 ( β=0.267, P=0.026) and AngⅡ ( β=0.268, P=0.001), while negatively correlated with ACE ( β=-0.320, P<0.001) and Ang1-7 ( β=-0.217, P=0.014). Basal luteinizing hormone was positively correlated with AngⅡ ( β=0.330, P=0.003), while negative correlated with Ang1-7 ( β=-0.395, P=0.002). Antral follicle count was positively correlated with Ang1-7 ( β=0.153, P=0.049), while negatively correlated with age ( β=-0.869, P<0.001) and ACE2 ( β=-0.082, P=0.004). Basal anti-Müllerian hormone was only negatively correlated with age ( β=-0.349, P<0.001). There was no correlation between RAS and basal estradiol, progesterone, prolactin, testosterone (all P>0.05). 4) Oocyte retrieval count was positively correlated with renin ( β=0.146, P=0.014), AngⅡ ( β=0.113, P=0.034) and Ang1-7 ( β=0.185, P=0.002), while negatively correlated with age ( β=-0.717, P<0.001); MⅡ oocyte maturation rate was positively correlated with AngⅡ ( β=0.207, P=0.019) and Ang1-7 ( β=0.217, P=0.026), while negatively correlated with age ( β=-0.518, P<0.001). There was no correlation between RAS and the rates of two pronuclei embryos, transplantable embryos, high-quality embryos (all P>0.05). Conclusion:The local RAS in ovarian follicles is affected by age and correlated with ovarian function and IVF laboratory outcome.

Objective:To understand and determine the biological properties of Chlamydia pneumonia (Cpn) hypothetical protein Cpn0423 and the mechanisms of which involved in Cpn0423-induced inflammatory response. Methods:The biological properties of Cpn0423 gene were analyzed using bioinformatic software. The subcellular localization of nucleotide-binding oligomerization domain-like receptor 2 (NOD2) in bone marrow-derived macrophages (BMDMs) was detected by confocal microscope. NOD2-siRNA was used to inhibit the expression of NOD2 at mRNA level. Cpn0423-induced macrophage inflammatory protein 2 (MIP-2) and IL-6 production in BMDMs were detected by ELISA. PCR was performed to detect Cpn0423 DNA in bronchoalveolar lavage fluid (BALF) of Cpn-positive patients.Results:The homology between Cpn0423 and other type Ⅲ secretion system effector proteins of Chlamydia ranged from 85% to 93%. NOD2-siRNA could effectively inhibit the expression of NOD2 at mRNA level in BMDMs ( P<0.001). Moreover, Cpn0423-induced production of MIP-2 [(920.5±99.1) pg/ml vs (130.1±11.5) pg/ml, P<0.001] and IL-6 [(266.2±58.4) pg/ml vs (165.7±21.5) pg/ml, P<0.001] in BMDMs were decreased following NOD2-siRNA pre-treatment. Cpn0423 DNA was detected in the BAlF of 83.3% (10/12) of Cpn-positive cases, but not in Cpn-negative cases. Conclusions:Cpn0423 induced inflammatory response in host cells through NOD2 pathway, which was closely related to the chronic inflammatory injury caused by Cpn.

Objective To investigate the inhibitory effect of baicalein on mycoplasma pneumonia and its the protective mecha -nism in body , and to provide scientific experimental basis for prevention and treatment of mycoplasma pneumoniae infection .Methods The mycoplasma pneumoniae and baicalein treated BALB /c mice lung tissues were stained with hematoxylin eosin (HE), and his-topathological grading .Minimum inhibitory concentration ( MIC) of baicalein on mycoplasma pneumonia was determined by real-time quantitative polymerase chain reaction ( PCR) .The expression of P 1 adhesion molecules mRNA and protein in lung tissue of BALB /c mice was determined with reverse transcription-PCR and Western blot .The expression of epidermal growth factor ( EGF) mRNA and protein in lung tissue was detected by quantitative RT-PCR and immunofluorescence .Results Baicalein significantly reduced the my-coplasma treated mice's lung tissue pathological score .The minimal inhibitory concentration of baicalein was 32 μg/ml.Baicalein sig-nificantly downregulated P 1 gene transcription and protein translation , and upregulated EGF gene transcription and protein expression . Conclusions Baicalein shows significant resistance to mycoplasma pneumoniae , and can protect the body against mycoplasma damage by inhibiting the expression of P 1 protein and promoting the expression of EGF protein .

Results of experimental studies with guinea pig showed that a strong blast may produce concussion of the vestibular apparatus. The parts injured include saccule and utricle and their maculas, semicircular canals and their cristas,and the nerves related to these organs.The most common pathological changes were hemorrhage, detachment of sensorial epithelium, collapse of membranous labyrinth, loss of oto-liths and degeneration of sensorial epithelial cells.The authors believe that these vestibular damages are produced by the combined action of strong noise and shock wave, being transmitted through the oral and round windows into the inner ear, producing a violent fluctuation of endolymph.