Objective　To investigate whether the expression regulation of regulatory gene Sigma factors (sigA-sigM) is related to isoniazid resistance phenotype in isoniazid-resistant Mycobacterium tuberculosis (MTB) caused by katG mutations, and to provide reference for the study of the molecular mechanism of isoniazid resistance. Methods　A total of 90 strains were collected from the patients undergoing first-line treatment at the Tianjin Tuberculosis Control Center during drug resistance testing from 2020 to 2022, of which 30 strains were sensitive strains without katG mutation, and 65 strains were isoniazid-resistant strains caused by katG mutation, including 11 strains resistant only to isoniazid, 24 strains resistant to both isoniazid and streptomycin, and 30 strains multidrug-resistant to isoniazid, streptomycin, and rifampicin. After the strains were collected on the isoniazid drug-containing medium, the RNA of the strains was extracted, and the relative expression levels of Sigma factors were detected by reverse transcription-polymerase chain reaction(RT-PCR). The expression differences of Sigma factors in different isoniazid drug-resistant phenotypes were analyzed by the Mann-Whitney U test. Results The gene expression levels of sigA, sigC, sigF, sigG, sigH, sigI, sigJ, sigK, sigL in isoniazid mono-resistant group were significantly higher than those in pan-isoniazid-sensitive group (Z=4.368, 5.701, 6.865, 4.021, 5.126, 2.670, 5.983, 4.701, 5.490, P all<0.001). The gene expression levels of sigA, sigC, sigF, sigG, sigH, sigI, sigJ, sigK, sigL in poly-resistance group were significantly higher than those in pan-sensitivity group (Z=-5.017, -4.670, -4.667, -5.456, -4.083, -5.393, -4.712, -6.971, -8.206, -5.211, P all<0.001). In multidrug-resistant (MDR) group, the gene expression levels of sigC, sigD, sigE, sigF, sigG, sigH, sigI, sigJ, sigK, sigL were significantly higher than those in pan-isoniazid-sensitive group (Z=-5.537, -4.003, -5.216, -7.328, -7.730, -5.658, -4.440, -6.036, -4.862, -4.312, P all<0.001). The expression levels of sigB, sigF, sigG showed statistically significant differences in gene expression between the isoniazid mono-resistant, isoniazid poly-resistant, and isoniazid multidrug-resistant groups (Z=10.139, 7.735, 14.532, P all<0.001). The expression rates of sigF, sigG, sigI, sigJ, and sigL in the isoniazid-resistant group were significantly higher than those in isoniazid sensitive group (χ2=17.410. 45.673. 57.661. 42.896. 26.363, P all<0.001). Conclusions sigF, sigG, sigI, sigJ, and sigL are associated with isoniazid resistance due to katG mutations.

Objective　To investigate the relationship between the degree of cervical lesions and the status of paired box-1 (PAX1) and tumor protein 63(TP63) gene promoter methylation in human papillomavirus (HPV)-positive patients with cervical lesions, as well as analyze their clinical significance. Methods Cervical tissue specimens were collected from 128 patients who were suspected of cervical lesions and HPV infection, and admitted to Qionghai People's Hospital between December 2021 and December 2022. According to pathological examination results, the patients were divided into the low-grade squamous intraepithelial lesion (LSIL) group (n=43), high-grade squamous intraepithelial lesion (HSIL) group (n=51) and cervical cancer group (n=34). The second-generation hybrid capture method was used for viral load. The degree of PAX1 and TP63 gene promoter methylation in each group was detected by bisulfite sequencing, and mRNA expression of PAX1 and TP63 was detected by real-time quantitative PCR. The diagnostic performance of the degree of PAX1 and TP63 methylation for cervical intraepithelial neoplasia (CIN2+) was evaluated. Results There were statistically significant differences in HR-HPV viral load between the groups (P>0.05). A total of 49 (38.28%) patients with PAX1 gene promoter methylation, and 55 (42.97%) patients with TP63 gene promoter methylation were detected among the 128 patients. The percentages of PAX1 and TP63 gene promoter methylation in the cervical cancer group, HSIL group and LSIL group were (67.65% and 73.53%), (43.14% and 49.02%) and (9.30% and 11.63%), with statistically significant differences between groups (P<0.05). The mRNA expression levels of PAX1 and TP63 in the cervical cancer group, HSIL group and LSIL group were [(0.34±0.08) and (0.45±0.13)], [(0.72±0.11) and (0.63±0.09)], [(1.04±0.09) and (0.87±0.11)], with statistically significant differences between groups (P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) values of PAX1, TP63 gene promoter methylation, and their combination for diagnosing CIN2+ were 0.793, 0.842, and 0.857, respectively. The sensitivity values were 77.78%, 83.33%, and 77.78%. The specificity values were 80.85%, 85.11%, and 93.62%. The combined detection can improve the specificity of diagnosis of CIN2+ lesions. Conclusions The degree of PAX1 and TP63 gene promoter methylation is closely related to cervical lesions in patients with HPV infection, which indicates that it can be used as potential auxiliary indicators for the clinical diagnosis of CIN2+lesions.

Objective To analyze and compare the auxiliary value and significance of γ-interferon release assay (IGRA) in the diagnosis of tuberculosis. Methods A retrospective analysis was conducted to collect the test results of 462 suspected tuberculosis patients who underwent IGRA detection in the outpatient department of Tianjin Tuberculosis Control Center from January 2020 to December 2021. According to the diagnostic results, they were divided into a tuberculosis group of 229 cases (203 cases of pulmonary tuberculosis and 26 cases of extrapulmonary tuberculosis) and a non-tuberculosis group of 233 cases. The auxiliary diagnostic value of IGRA for tuberculosis was analyzed and compared with two methods of Mycobacterium tuberculosis culture and Xpert MTB/RIF. Results The positive rates of IGRA, Mycobacterium tuberculosis culture, and Xpert MTB/RIF in TB patients were 76.42%, 29.26% and 40.62%, respectively, compared with the non-TB group (38.20%, 0.00%, 0.00%), with statistically significant differences (P<0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of IGRA alone in the detection of tuberculosis were 76.42%, 61.80%, 69.29%, and 72.73% respectively, those of Mycobacterium tuberculosis culture were 29.26%, 98.28%, 94.37%, and 63.43%, and those of Xpert MTB/RIF were 40.60%, 100%, 100%, and 63.14%. The positive rates of IGRA were 76.85% and 73.08% in patients with pulmonary tuberculosis and extrapulmonary tuberculosis, respectively, with no statistical significance (P>0.05). The positive rates of IGRA in bacterial positive patients and non-tuberculosis patients were 79.34% and 38.20%, respectively, with statistical significance (χ2=54.526, P<0.001). The positive rates of IGRA in patients with and without tuberculosis were 73.15% and 38.20%, respectively, with significant difference (χ2=36.456, P<0.001). Conclusions IGRA has a relatively high sensitivity in the diagnosis of tuberculosis and also has certain advantages in the screening of extrapulmonary tuberculosis and mycobacterium-negative It provides important reference basis for the clinical diagnosis of tuberculosis.

Objective:To explore the sleep status and impact factor analysis of patients in clinical trials of antineoplastic drugs, and provide a basis for improving the sleep status and impact analysis of patients in clinical trials of antineoplastic drugs.Methods:From April to May 2023, 107 oncology patients in the Phase I Clinical Trial Ward of the Affiliated East Hospital of Tongji University were selected as the research objects by convenient sampling method. The general information questionnaire, Pittsburgh Sleep Quality Index Scale (PSQI), Numeric rating scale (NRS), Generalized Anxiety Disorder Scale (GAD-7) and Depression Self-Ration Tool Scale (PHQ-9). Multivariate Logistic regression analysis methods were used to carry out a cross-sectional investigation and the relevant factors affecting patients′sleep.Results:Totally 103 questionnaires were effectively collected. The 103 patients′ age ranged from 20 to 75 years old, including 61 males and 42 females. 47.57% (49/103) patients in clinical trials of antineoplastic drugs had abnormal sleep. The average score of patients (PSQI) (7.66 ± 3.93) was higher than the average score of the domestic norm (3.88 ± 2.52), and there was significant statistical difference ( t = 9.76, P<0.01). Logistic regression analysis showed that pain ( OR = 3.004, 95% CI 1.135-7.948, P<0.05) and trial cycle ( OR = 0.432, 95% CI 0.191-0.978, P<0.05) were significant risk factors for abnormal sleep quality. Conclusions:The incidence of abnormal sleep quality in patients of clinical trials of antineoplastic drugs is high, but the sleep quality is poor. The factors that affect the sleep quality of patients in clinical trials of antineoplastic drugs are mainly related to the patient′s trial cycle and cancer pain. According to these characteristics, individualized programs should be developed to improve the sleep quality of patients with advanced cancer, so as to improve the quality of life of patients with advanced cancer.

Aquaporin 9 (AQP9),one of members of the cell membrane protein family,plays an important role in maintaining metabolism and water balance in vivo.AQP9 could also play an importan role in development of tumors,such as migration,metastasis and apoptosis of tumor cells.In addition,AQP9 is of great significance in judging prognosis of tumors.

ObjectiveTo establish a vaginal self-sampling HPV cervical cancer screening model in Hainan Province, to analyze the application of p16 protein detection in HPV positive and non-HPV16 /18 shunt screening. MethodsFrom January 2019 to September 2022, a total of 200 women from the targeted population was randomly selected for vaginal self-sampling HPV typing test to screen cervical cancer using randomized numeric table method, followed by cervical cytology sampling for cytology p16 protein detection. Postoperative pathological examination was used as the gold standard. Multivariate logistic regression analysis was used to analyze the influencing factors of HPV positive detection rate in cervical lesions, and the nomogram model was constructed simultaneously. The receiver operating characteristic(ROC) curve and calibration curve were used for evaluating the accuracy of the nomogram model. Differences in the distribution of self-sampled HPV-positive and HPV infected genotypes were recorded, and the application of p16 protein detection in HPV-positive and non-HPV16/18 shunt screening was analyzed. ResultsAged ≥40 years, BMI ≥28.00 kg·m^-2, number of sexual partners ≥2, frequency of sexual life ≥10 times·month^-1, bleeding from sexual intercourse, and age of first sexual intercourse <22 years were the risk factors for HPV positive of cervical lesions (all P<0.001). The results of ROC curve and calibration curve showed that the area under ROC curve (AUC) was 0.874 (95%CI: 0.823‒0.907, P<0.05), the sensitivity was 0.835, the specificity was 0.847, and the Youden index was 0.672, indicating a good fit of the model. Results of vaginal self-sampling HPV test showed that the positive rate of HPV was 86.50% (173/200). HPV high-risk infection types mainly included HPV16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, 68, 73, and 82. Single HPV infection accounted for 95.95% (166/173), 2.89% (5/173) were infected with two types of HPV, and 1.16% (2/173) were infected with three or more types of HPV. Colposcopic pathologic diagnosis was used as the gold standard, and the results showed that the accuracy of p16 protein detection in the diagnosis of cervical cancer was 93.50% (187/200), with a sensitivity of 96.53% (167/173), and a specificity of 74.07% (20/27). The negative and positive predictive value were 76.92% (20/26) and 95.98% (167/174), respectively. The results of shunt screening showed that there were 80 cases infected with HPV16, 79 cases infected with HPV18 and 41 cases of non-HPV16/18, with a sensitivity of 90.91%, 90.32% and 86.67%, a specificity of 71.43%, 64.71% and 72.73%, a negative predictive value of 62.50%, 64.71% and 66.67%, a positive predictive value of 93.75%, 90.32% and 89.66%, and an accuracy of 87.50%, 84.81% and 82.93%, respectively. The specificity and accuracy of p16 positive screening for cervical cancer were significantly higher than that of HPV positive detection, but the false positive rate was significantly lower than that of HPV positive detection. The AUCs of HPV positive, p16 positive and combination of the two detection methods for cervical cancer were 0.603, 0.822 and 0.907, respectively. ConclusionVaginal self-sampling HPV testing is a widely accepted mode for cervical cancer screening. Cervical cytology p16 protein detection is important for self-sampled HPV positive and shunt screening of non-HPV16/18.