[China's countermeasures in the context of Global Tuberculosis Prevention Action].

In order to speed up the expansion of global tuberculosis (TB) preventive treatment (TPT), the WHO released "CALL TO ACTION 2.0 A GLOBAL DRIVE TO SCALE UP TB PREVENTION" in June 2021, calling on governments and other stakeholders to increase investment, expand the TB screening and diagnosis, and accelerate coverage of TB preventive treatment. To ensure reach the targets of TPT committed by Heads of State at the UN High Level Meeting on TB (UN-HLM) in 2018. The author systematically analyzed the current situation, the progress, the necessity and urgency of carrying out TPT in China, and put forward the countermeasures and suggestions of TPT in China.

[A preliminary study on molecular target identification of drugs in individualized treatment of malignant solid tumors in children].

Objective: To explore the role of drug-related molecular target identification in the individualized treatment of malignant solid tumors in children. Methods: The clinical data of 40 patients diagnosed with malignant solid tumors from Beijing Tongren Hospital, Capital Medical University, between June 2017 and March 2019 were retrospectively analyzed. Immunohistochemistry, polymerase chain reaction and sequencing methods were used to determine the expression levels and mutations of tumor drug molecular targets, and to compare the efficiency as well as the incidence of toxic side effects of chemotherapy using anti-tumor drugs with various molecular targets. Results: A total of 4 tumor drug-related targets were identified in 40 tumor tissue samples, namely DNA topoisomerase-ⅡA (TOPOⅡA), ß(3)-tubulin (Tubulinß(3)), DNA topoisomerase-Ⅰ(TOPOⅠ) and dihydrofolate reductase gene polymorphisms [DHFR (C829T)]. The effective rates of platinum-based agents, methotrexate, irinotecan, vinblastine and anthracycline for malignant solid tumors in children were 90.0% (36/40), 85.0% (34/40), 70.0% (28/40), 67.5% (27/40), 62.5% (25/40), respectively. The effective rates of chemotherapy with irinotecan, methotrexate, and vinblastine in mesenchymal tumors were 68.9% (20/29), 62.1% (18/29), 68.9% (20/29), respectively, which were considerably higher than 18.2% (2/11), 36.4% (4/11) and 36.4% (4/11) in non-mesenchymal tumors, with significant differences (χ(2)=5.487, 15.345, 17.278, all P<0.05). The effective rate of chemotherapy of platinum-based drugs for non-mesenchymal tumors was 72.3% (8/11), which was significantly higher than 58.6% (17/29) in mesenchymal tumors, and the difference was statistically significant (χ(2)=11.231, P<0.05). The intensity of toxic side effects in order from high to low was anthracycline > platinum > methotrexate > vinblastine > irinotecan. Conclusion: Tumor drug-related molecular targets and the sensitivity of tumors of different origins to the same anti-tumor drug as well as side effects are predicted, which provides a theoretical and clinical basis for individualized treatment of malignant tumors in children.

[Combination of CT mulitplane 3D reconstruction, radial endobronchial ultrasound and rapid on-site evaluation for diagnosing peripheral solitary pulmonary nodules].

Objective: To evaluate the diagnostic efficiency of combination of CT multiplane 3D reconstruction (CT-3DR), radial endobronchial ultrasound (R-EBUS), and rapid on-site evaluation (ROSE) for peripheral solitary pulmonary nodules (SPN). Methods: A total of 176 patients with peripheral solitary pulmonary nodule were included from the Nanjing Chest Hospital from March 2016 to March 2017. According to different methods, all the patients were divided into four groups: EG (i.e. R-EBUS+Guiding sheath (GS))group, CTE (i.e. CT-3DR+R-EBUS) group, RE (i.e. ROSE+R-EBUS) group, and triad (i.e. CT-3DR+ROSE+R-EBUS) group. Sampling was performed by transbronchial lung biopsy. The diagnostic yield and complications, procedure time and influencing factors in these four groups were retrospectively analyzed. The value of ROSE and combination of CT-3DR+ROSE+R-EBUS in diagnosis for SPN also was evaluated. Results: The diagnostic yield for total SPNs among four groups were 70.5% in EG group, 70.0% in CTE group, 69.0% in RE group and 74.0% in triad group, respectively. There was no significant difference among four groups (all P>0.05). The procedure time of EG group, CTE group, RE group and triad group were (34.0±6.3), (26.6±6.8), (27.2±7.8) and (19.4±5.4) min, respectively. The procedure time was the shortest in triad group compared with the other three groups (all P<0.001) and the time of CTE and RE groups were significantly shorter than the EG group (both P<0.001). The coincidence rates of CT-3DR navigation position with target bronchus were 87.5% in CTE group and 90.0% in triad group with no significant difference between these two groups (P>0.05). The diagnostic yield was higher for SPNs with their major diameter ≥2 cm than those with their major diameter<2 cm in all four groups (all P<0.05). The positive diagnostic yield was higher with ultrasonic probe located within SPN lesion than the probe adjacent to or deviated the lesion in all four groups (all P<0.05). In EG and RE groups, for those SPNs with the distance between the lesion and pleura≥2 cm, the diagnostic yield were higher than those withe the distance<2 cm (P<0.05) but no similar phenomenon was observed in CTE and triad groups. No significant correlation was detected between the diagnostic yield and the density of SPN lesions among four groups (all P>0.05). ROSE was used in RE and triad groups. The coincidence rate of ROSE with histopathology was 82.6% and the value of Kappa was 0.608. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of ROSE were 0.818, 0.846, 0.931 and 0.647, respectively. Conclusions: CT-3DR navigation and ROSE help to improve the diagnostic efficiency of R-EBUS for SPN. Combination of CT-3DR, R-EBUS and ROSE is of diagnostic value for peripheral SPN and with significant shortening of procedure time.

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case-control study.

BACKGROUND: Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC. METHODS: We conducted a case-control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview. RESULTS: Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin. CONCLUSION: These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.

Genomic changes at the early stage of somatic hybridization.

A broad spectrum of genetic and epigenetic changes is induced by wide hybridization and subsequent polyploidization, but the timing of these events remains obscure because early hybrid cells are very difficult to harvest and analyze. Here, we used both cytological and genetic marker approaches to analyze the constitution of very young somatic hybrid cells between japonica rice (Oryza sativa L. subsp japonica) and indica rice (Oryza sativa L. subsp indica) and between japonica rice and bread wheat (Triticum aestivum L.). Chromatin elimination, simple sequence repeats, and retrotransposon profile deletions were already apparent within six days of the fusion event. The evidence we have presented suggests that genomic changes induced by genomic shock occur soon after the formation of hybrid cells.

[Clinical characteristics and CT findings of Pneumocystis Jirovecii pneumonia in 46 cases with hematological diseases].

Objective: To summarize the original CT features of Pneumocystis Jirovecii pneumonia in patients with hematological diseases. Methods: A retrospective analysis was carried out in 46 patients with proven pneumocystis pneumonia (PJP) in the Hospital of Hematology, Chinese Academy of Medical Sciences between January 2014 and December 2021. All patients had multiple chests CT and related laboratory examinations, imaging typing were conducted based on the initial CT presentation, and the distinct imaging types were analyzed against the clinical data. Results: In the analysis, there were 46 patients with proven pathogenesis, 33 males, and 13 females, with a median age of 37.5 (2-65) years. The diagnosis was validated by bronchoalveolar lavage fluid (BALF) hexamine silver staining in 11 patients and clinically diagnosed in 35 cases. Of the 35 clinically diagnosed patients, 16 were diagnosed by alveolar lavage fluid macrogenomic sequencing (BALF-mNGS) and 19 by peripheral blood macrogenomic sequencing (PB-mNGS) . The initial chest CT presentation was categorized into 4 types, including ground glass (GGO) type in 25 cases (56.5%) , nodular type in 10 cases (21.7%) , fibrosis type in 4 cases (8.7%) , and mixed type in 5 cases (13.0%) . There was no substantial discrepancy in CT types among confirmed patients, BALF-mNGS diagnosed patients and PB-mNGS diagnosed patients (χ(2)=11.039, P=0.087) . The CT manifestations of confirmed patients and PB-mNGS diagnosed patients were primarily GGO type (67.6%, 73.7%) , while that of BALF-mNGS diagnosed patients were nodular type (37.5%) . Of the 46 patients, 63.0% (29/46) had lymphocytopenia in the peripheral blood, 25.6% (10/39) with positive serum G test, and 77.1% (27/35) with elevated serum lactate dehydrogenase (LDH) . There were no great discrepancies in the rates of lymphopenia in peripheral blood, positive G-test, and increased LDH among different CT types (all P>0.05) . Conclusion: The initial chest CT findings of PJP in patients with hematological diseases were relatively prevalent with multiple GGO in both lungs. Nodular and fibrosis types were also the initial imaging findings for PJP.

[HIV infection rate, high-risk behavior and pre-exposure prophylaxis/post-exposure prophylaxis in men who have sex with men in Beijing].

Objective: To understand the incidence of HIV infection, high risk behaviors and pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) utilization in men who have sex with men (MSM) in Beijing. Methods: Sample size was estimated to be 1 227 persons and 207 person year respectively in the survey and the cohort by using Epi Info 7.0 software. Using convenient sampling method, MSM were recruited by using Wechat app. Questionnaire was completed online to collect the information about demographic characteristics, high risk behavior, and utilization of PrEP/PEP of the MSM. MSM collected dry blood spot (DBS) samples by themselves, and mailed the DBS samples to laboratory for HIV nucleic acid testing. Open cohort was established and those with HIV negative nucleic acid testing results were followed up. Non-conditional binary logistic regression method was used to identify the associated factors for high risk anal sex in the last month and having multiple homosexual partners in the last month. Results: A total of 1 147 MSM were recruited, and follow up for 236 person years was conducted in 956 MSM with negative HIV nucleic acid testing results. The detection rate of new HIV infection was 1.3 per 100 person-years (3/236). During the last month, the proportions of consistent condom use in anal sex and oral sex were 50.7% (238/469) and 4.9% (23/469). In the MSM, 5.9% (43/723) had sex with HIV positive partners in the last month. 9.8% (103/1 049) used PrEP, and 8.7% (91/1 049) used PEP. The proportion of consistent condom use in PrEP and PEP were 34.3% (24/70) and 72.2% (39/54) respectively. Logistic regression analysis revealed that compared with those who used no PrEP/PEP, those who used PrEP/PEP were more likely to have unprotected anal sex in the last month (aOR=3.16, 95%CI:1.45-7.18), and more likely to have multiple homosexual partners in the last month (aOR=2.64, 95%CI:1.19-6.30), and compared with those who used no Rush Popper or drugs in the last month, those who used Rush Popper or drugs in the last month were more likely to have unprotected anal sex in the last month (aOR=2.34, 95%CI:1.67-3.30), and more likely to have multiple homosexual partners (aOR=2.42,95%CI:1.76-3.33). Conclusions: It is necessary to strengthen the health education to promote condom use and introduce the harm of drug use in MSM. In PrEP and PEP services, it is still necessary to suggest consistent condom use for MSM.

[Metagenomic next-generation sequencing of plasma for the identification of bloodstream infectious pathogens in severe aplastic anemia].

Objective: To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection. Methods: From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy. Results: ①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion: mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

Polymorphisms of the ATP1A1 gene associated with mastitis in dairy cattle.

Mastitis affects the concentrations of potassium and sodium in milk. Since sodium-potassium adenosine triphosphatase (Na(+), K(+)-ATPase) is critical for maintaining the homeostasis of these two ions, and is involved in cell apoptosis and pathogenesis, we presumed that polymorphism of the ATP1A1 gene, which encodes the bovine Na(+), K(+)-ATPase α1 subunit could be associated with mastitis. The ATP1A1 gene was analyzed in 320 Holstein cows using PCR low ionic strength single-strand conformation polymorphism (PCR-LIS-SSCP) and DNA sequencing methods. A C/A SNP was identified at nucleotide position -15,739 in exon 17 of the ATP1A1 gene, but it did not induce any change in amino acids. We examined a possible association of polymorphism of the ATP1A1 gene with somatic cell score and 305-day milk yields. Individuals with genotype CC in ATP1A1 had significantly lower somatic cell scores and 305-day milk yields than those with genotype CA. We also examined changes in Na(+), K(+)-ATPase activity of red cell membranes. The Na(+), K(+)-ATPase activity was significantly higher in dairy cows with genotype CC compared to the other two genotypes, and the Na(+), K(+)-ATPase activity of the resistant group was significantly higher than that of the susceptible group in dairy cows. We conclude that this polymorphism has potential as a marker for mastitis resistance in dairy cattle.