Background:Serum pro-gastrin releasing peptide (proGRP) is a well-recognized diagnostic marker for small cell lung cancer (SCLC). Pleural effusion is common in patients with advanced SCLC. The diagnostic accuracy of pleural proGRP for malignant pleural effusion (MPE) has not yet been established. This study aimed to evaluate the diagnostic accuracy of pleural proGRP for MPE. Methods:We prospectively recruited patients with undiagnosed pleural effusions from two centers (Hohhot and Changshu). An electrochemiluminescence immunoassay was used to detect pleural fluid proGRP. The diagnostic accuracy of proGRP for MPE was evaluated using a receiver operating characteristic (ROC) curve. Results:In both the Hohhot (n=153) and Changshu (n=58) cohorts, pleural proGRP in MPE patients did not significantly differ from that in patients with benign pleural effusions (BPEs) (Hohhot, P=0.91; Changshu, P=0.12). In the Hohhot and Changshu cohorts, the areas under the curves (AUCs) of proGRP were 0.51 [95% confidence interval (CI): 0.41-0.60] and 0.62 (95% CI: 0.47-0.77), respectively. However, patients with SCLC-induced MPE had significantly higher proGRP levels than those with BPE and other types of MPE (P=0.001 for both). In the pooled cohort, the AUC of proGRP for SCLC-induced MPE was 0.90 (95% CI: 0.78-1.00, P=0.001). At a threshold of 40 pg/mL, proGRP had a sensitivity of 1.00 (95% CI: 0.61-1.00) and specificity of 0.59 (95% CI: 0.52-0.66). The positive likelihood ratio was 2.61 (95% CI: 1.99-3.41), and the negative likelihood ratio was 0. Conclusions:Pleural proGRP has no diagnostic value for MPE, but has high diagnostic accuracy for SCLC-induced MPE. In patients with proGRP levels <40 pg/mL, MPE secondary to SCLC can be excluded.

Objective: This study aimed to identify key factors influencing post-operative pathologic escalation in Chinese women with histologic cervical low-grade squamous intraepithelial lesions (LSILs) undergoing cervical conization and construct a predictive nomogram model. Material and Methods: A retrospective analysis was conducted on 107 patients with LSIL from Bengbu City, Anhui Province, China, who underwent cervical conization at the First Affiliated Hospital of Bengbu Medical College from January 2019 to January 2023. Patients were categorized into groups based on post-operative pathological upgrade. Univariate and multivariate logistic regression analyses identified independent risk factors. A nomogram model was developed and evaluated for clinical predictive ability using calibration curves, the Hosmer-Lemeshow test, and decision curve analysis (DCA). Results: Post-operative pathological upgrades were experienced by 39.3% of patients with LSIL. Independent risk factors for escalation included positive human papillomavirus (HPV)16/18/52/53/58 high-risk types (P P < 0.05, OR = 4.95, 95% CI = 1.32-18.46), ThinPrep Cytology Test (TCT) results indicating high-grade squamous intraepithelial lesion (HSIL)/atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H)/atypical glandular cells ( AGC) (P P < 0.01, OR = 13.12, 95% CI = 3.10-55.50), and cervical transformation zone (TZ) type III (P P < 0.05, OR = 6.10, 95% CI = 1.65-22.56). Based on these factors, the nomogram demonstrated good differentiation and calibration (area under the curve [AUC]: 0.744, 95% CI: 0.674-0.839). DCA indicated high clinical predictive value. Conclusion: HPV16/18/52/53/58 high-risk types, TCT HSIL/ASC-H/AGC, and colposcopic cervical TZ type III are independent risk factors for post-operative pathologic escalation in LSIL. Consideration of pre-operative HPV, TCT results, and cervical TZ type is crucial for effective triage and patient management. The constructed nomogram provides a practical tool for risk assessment of patients with LSIL undergoing cervical conization.

BACKGROUND:Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS:This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS:One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS:Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Background:Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods:This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results:We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions:Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.

IntroductionPleural effusion is common in clinical practice, and its differential diagnosis remains challenging for clinicians. This study investigates the diagnostic value of apolipoprotein E (apoE) in patients with undetermined pleural effusion.MethodsThis prospective, double-blind study enrolled 152 patients with undiagnosed pleural effusion. Their pleural fluid apoE levels were measured, and a receiver operating characteristics (ROC) curve was used to evaluate the diagnostic accuracy of apoE. Decision curve analysis (DCA) was used to assess apoE's net benefit. Subgroup analyses were performed to investigate the effect of age on the diagnostic accuracy of apoE.ResultsAmong the included participants, 23 had heart failure (HF). HF patients had the lowest apoE level among pleural effusion patients. The area under the curve (AUC) of apoE for HF was 0.79 (95% CI: 0.69-0.89). At the threshold of 40 mg/L, the sensitivity and specificity of apoE were 0.96 (95% CI: 0.87-1.00) and 0.33 (95% CI: 0.25-0.42), respectively. The decision curve for apoE was above reference lines. The AUC of apoE decreased in older patients.ConclusionPleural fluid apoE has moderate diagnostic value for HF and has net benefits in patients with undiagnosed pleural effusion. The diagnostic accuracy of apoE decreases with age.

Background: Pleural fluid (PF) carcinoembryonic antigen (CEA) is a widely used diagnostic marker for malignant pleural effusion (MPE). Recent studies revealed that PF to serum CEA was also a promising diagnostic parameter for MPE. Objective: We aimed to investigate whether PF to serum CEA ratio and delta CEA (PF minus serum CEA) provided added value to PF CEA in diagnosing MPE. Methods: Patients with pleural effusion in a retrospective cohort (BUFF) and a prospective cohort (SIMPLE) were included. The clinical characteristics of the patients were extracted from their medical records. The diagnostic value of CEA ratio and delta CEA was estimated by a receiver operating characteristics (ROC) curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: A total of 148 patients in the BUFF cohort and 164 patients in the SIMPLE cohort were enrolled. The BUFF cohort had 46 MPE patients and 102 benign pleural effusion (BPE) patients, and the SIMPLE cohort had 85 MPE patients and 79 BPE patients. In both cohorts, MPE patients had significantly higher PF CEA, serum CEA, CEA ratio, and delta CEA. The area under ROC curves (AUCs) of PF CEA, CEA ratio, and delta CEA were 0.78 (95% CI: 0.67–0.88), 0.80 (95% CI: 0.72–0.89) and 0.83 (95% CI: 0.75–0.91) in the BUFF cohort, and 0.89 (95% CI: 0.83–0.94), 0.86 (95% CI: 0.80–0.92), and 0.84 (95% CI: 0.78–0.91) in the SIMPLE cohort. The differences between the AUCs of PF CEA, CEA ratio, and delta CEA did not reach statistical significance. The continuous NRI and IDI of CEA ratio and delta CEA were <0. Conclusion: CEA ratio and delta value cannot provide added diagnostic value to PF CEA. The simultaneous determination of serum and PF CEA should not be adopted in clinical practice.

BACKGROUND:Tumour immune microenvironment (TIME) has long been a key direction of tumour research. Understanding the occurrence, metastasis and other processes of cervical cancer (CC) is of great significance in the diagnosis and prognosis of tumours. METHODS:Here, this study applied the univariate Cox regression model to determine the prognostic association of immune and hypoxia signature genes in CC, and used Least Absolute Shrinkage and Selection Operator (LASSO) Cox method to build immune and hypoxia related risk score model to uncover the immune signature of the TIME of CC. Moreover, we used in vitro experiment to validate the expression level of signature genes. Notably, we assessed the predictive effect of anti-PD1/PDL1 immunotherapy using risk score model. RESULTS:Through the LASSO Cox regression model, we obtained 12 characteristic genes associated with the prognosis of CC, and also associated with immunity and hypoxia. Interestingly, the high-risk group had the properties of high hypoxia and low immunity, while the low-risk group had the properties of low hypoxia and high immunity. In the low-risk group, patients lived longer and had a significant therapeutic advantage of anti-PD-1 immunotherapy. CONCLUSIONS:Established risk scores model can help predict response to anti-PD-1 immunotherapy of CC.

Background: The in vitro stability assessment is essential for investigating the diagnostic accuracy of pleural biomarkers. This study aimed to investigate the long-term stability of pleural fluid carcinoembryonic antigen (CEA) at -80 degrees C to -70 degrees C. In addition, we analyzed the effects of frozen storage on the diagnostic accuracy of CEA for malignant pleural effusion (MPE).Methods: Pleural fluid CEA of participants in two prospective cohorts were stored at -80 degrees C to -70 degrees C for 1-3 years. The CEA level in the stored specimen was mea-sured with an immunoassay, and its level in the fresh specimen was extracted from medical records. The Bland-Altman method, Passing-Bablok regression, and Deming regression were used to analyze the agreement of CEA between the fresh and frozen pleural fluid. In addition, we used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CEA in the fresh and frozen specimens for MPE.Results: A total of 210 participants were enrolled. The median CEA levels in frozen and fresh pleural fluid specimens were similar (frozen, 2.32 ng/mL; fresh, 2.59 ng/mL; p < 0.01). The slopes and intercepts in the Passing-Bablok regression (intercept 0.01, slope 1.04) and Deming regression (intercept 0.65; slope 1.00) were not statistically significant (p > 0.05 for all). No significant difference was observed between the area under the ROC curves of CEA in the fresh and frozen specimens (p > 0.05 for all).Conclusion: Pleural fluid CEA is seemingly stable when stored at -80 degrees C to -70 degrees C for 1-3 years. Frozen storage does not significantly affect the diagnostic accuracy of CEA for MPE.

Hepatitis C is a serious infectious disease caused by the hepatitis C virus (HCV). HCV genotypes (GT) and subtypes are closely related to geographical distribution. Studies on the distribution of HCV genotypes can help to understand the regional epidemiology and genotype distribution and provide benefits in the treatment for hepatitis C. To provide information about the distribution of HCV genotypes as well as improved prevention and treatment of hepatitis C, we aimed to classify the distribution of HCV genotypes among Mongolian and Han patients with hepatitis C in Inner Mongolia over the past 5 years. Peripheral blood samples of patients with HCV were collected for gene sequencing. To analyze the HCV genotype distribution and possible influencing factors, we determined the viral load and ratios of various genotypes. We found that the most prevalent genotype in Inner Mongolia was 1b, followed by GT2a, GT3a, GT3b, and GT6a. The prevalence of HCV among Mongolian patients was significantly higher than the prevalence in their Han counterparts (χ2 = 16.64, P = .000). There was no significant difference in viral load according to sex among HCV genotypes. However, the viral load of GT 1b was significantly higher than that of GT 2a (F = 3.51, P = .008). The viral load of GT 1b among ethnic Mongolians was significantly higher than that among Han patients (t = 2.28, P = .044). The present study's findings can serve as a basis for developing a personalized treatment for hepatitis C among patients in Inner Mongolia.

Background and Objective:Green tea is a popular beverage worldwide and has numerous health-promoting properties. Accumulating evidence indicates that green tea has preventive and therapeutic effects on lung cancer. This study aimed to investigate the association between green tea consumption and lung cancer.Methods:We performed a narrative review to summarized the association between green tea consumption and lung cancer.Key Content and Findings:Green tea consumption is known to decrease lung cancer risk in the general population, as indicated by meta-analyses of observational studies. Two active components of green tea, theabrownin and (-)-epigallocatechin gallate (EGCG), mediate the antitumor activity of green tea. Theabrownin promotes apoptosis, induces cell cycle arrest, and inhibits the migration, clone formation, and proliferation of lung cancer cell lines in vitro and in vivo. EGCG inhibits lung cancer cell proliferation and promotes apoptosis, agenesis, and epithelial-mesenchymal transition (EMT). In addition, EGCG sensitizes lung cancer cells to cisplatin and tyrosine kinase inhibitors (TKIs). The possible molecular mechanisms underlying the antitumor activity of EGCG and theabrownin were reviewed.Conclusions:Observational studies have indicated that green tea has preventive effects on lung cancer. In vitro and animal studies have indicated that green tea has therapeutic effects on lung cancer. Further clinical trials are needed to illustrate the therapeutic effects of green tea or its active components (i.e., theabrownin, EGCG) on lung cancer.

Background:Tumor-associated macrophages (TAMs) affects the outcomes of non-small cell lung cancer (NSCLC). NSCLC cells released exosomes to suppress the antitumor activity of TAMs. MiR-146a is a critical regulator in TAM polarization. We hypothesized that NSCLC cells released exosomal miR-146a to regulate TAM polarization and thus affected its antitumor activity.Methods:We used H1299 cells-derived exosomes to stimulate THP-1 cells that was pretreated with phorbol 12-myristate 13-acetate (M0 macrophage). Flow cytometry and reverse transcription-quantitative polymerase chain reaction (PCR) were used to determine the polarization of macrophages. The conditioned medium of exosome-treated M0 cells was used to culture H1299 cells, and the Cell Counting Kit-8, Ki67, transwell and scratch wound assays were used to determine the biological behavior of H1299 cells. To investigate whether exosomal miR-146a regulates TAM macrophages through targeting tumor necrosis factor receptor-associated factor 6 (TRAF-6) and interleukin-1 receptor-associated kinase 1 (IRAK-1), we used small interfering RNA to knockdown the expressions of them.Results:Upregulation of miR-146a inhibited M1 polarization and thus impaired the antitumor activity of TAMs. Exosomes released by H1299 cells can be taken by M0 macrophage, and they upregulated the expression of miR-146a in M0 macrophage. The exosome suppresses M1 polarization by exosomal miR-146a. TRAF-6 and IRAK-1 mediated the inhibitive effects of exosomal miR-146a on M1 polarization.Conclusions:NSCLC cells released exosomal miR-146a to inhibit the expressions of TRAF-6 and IRAK-1 in TAMs, resulting in the impaired antitumor activity of TAMs. NSCLC cell-derived exosomal miR-146a represents a novel therapeutic target for NSCLC treatment.