[Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A].

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

[Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study].

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

[Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database].

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

[Analysis of tuberculosis epidemiological characteristics and drug resistance among the floating population in Beijing in 2019].

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.

[Research progress of single-cell sequencing technology in liver diseases].

Liver disease is one of the most burdensome diseases in the world. Therefore, new technologies are needed to study its pathogenesis in depth; however, because of its complex pathogenesis, there are relatively limited treatment options. Single-cell sequencing (SCS), as an emerging sequencing method, reflects the heterogeneity between cells by sequencing the genome, transcriptome, and epigenome of a single cell, thereby revealing the complex mechanisms of disease occurrence and development. The application of SCS in the study of liver diseases will enrich our understanding of the pathogenesis of liver diseases and provide a new direction for exploring the diagnosis and treatment. This article mainly reviews the research progress of SCS technology in liver diseases.

Efficacy of Traditional Chinese Herbs combined with bioelectrical stimulation on patients with kidney deficiency and blood stasis type thin endometrium: a retrospective observational study.

OBJECTIVE: This study aimed to investigate the efficacy of Traditional Chinese Herbs (TCH) combined with bioelectrical stimulation (BES) on patients with kidney deficiency and blood stasis type thin endometrium. PATIENTS AND METHODS: A retrospective observational study was conducted on 83 patients diagnosed with thin endometrium, treated in our hospital from August 2019 to August 2021. The clinical data of the patients were reviewed, and 60 eligible patients were categorized into two groups based on the treatment they received: the TCH-BES group (n=30, patients received Femoston, TCH and BES treatment) and the control group (n=30, patients received Femoston only). The endometrial thickness (EMT), uterine artery resistance index (RI) and pulsatility index (PI), serum reproductive hormone levels, traditional Chinese medicine (TCM) syndrome scores, and clinical pregnancy outcomes between the two groups were compared. Continuous data were described as mean ± standard deviation (X- ± S). Student's t-test was used for comparison between the two groups and paired-sample t-test was used for comparison within the same group before and after the treatment. RESULTS: A total of 60 patients with thin endometrium, aged 20-35 years (average, 31.67±3.19 years), were included in this study. After the treatment, the EMT, E2 and progesterone (P) levels of the TCH-BES group were higher than that of the control group (p<0.001, p<0.05 and p<0.001, respectively), the PI, RI level and TCM syndrome scores of the TCH-BES group were lower than those of the control group (p<0.001). The clinical efficacy and pregnancy rate in the TCH-BES group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: TCH combined with EBS has a satisfactory efficacy on patients with kidney deficiency and blood stasis type thin endometrium, and improves EMT, E2 and P levels, reduces PI, RI and TCM syndrome, and eventually leads to a favorable clinical pregnancy outcome.

[Effects of Porphyromonas gingivalis injected through tail vein on the expressions of biomarkers in neural stem cells and neurons of wild-type rats hippocampus].

Objectives: To study the effects of Porphyromonas gingivalis (Pg) injected through tail vein on the molecular expression levels of biomarkers of neural stem cells (NSC) and neurons in the hippocampus of wild-type adult rats, and the effects on hippocampal neurogenesis. Methods: Eighteen male Sprague-Dawley (SD) rats were randomly divided into 3 groups based on the table of random numbers (n=6 in each group). In low-intensity group and high-intensity group, rats were injected intravenously through tail vein with 200 µl Pg ATCC33277 [1.0×103 and 1.0×108 colony forming unit (CFU), respectively] 3 times per week for 8 weeks. In the sham group, 200 µl of phosphate buffer saline (PBS) was given instead. Behavioral tests: the navigation and the exploration tests using Morris water maze (MWM) were applied to evaluate learning and memory ability of rats. Immunohistochemistry was performed to detect cells positively expressing nestin, doublecortin (DCX) and neuronal nuclei (NeuN) in the subgranular zone (SGZ) of rats in each group. Western blotting was used to evaluate the expression levels of nestin, DCX and NeuN in rat hippocampus. Results: Learning and memory abilities: on day 5 of navigation test, the lagency time was 22.83 (16.00, 38.34) s in the high-intensity group, significantly longer than the sham group [5.59 (5.41, 6.17) s] (t=-11.17, P<0.001). There were no significant differences between the low-intensity group [9.85 (8.75, 21.01) s] and the sham group (t=-6.83, P=0.080). Results in the exploration test showed that, in the high-intensity group, the number of fime crossing over the previous platform area within 60 s was 1.50 (1.00, 2.00), significantly less than the sham group [4.00 (2.75, 4.00)] (t=9.75, P=0.003); no significant differences between the low-intensity group [2.50 (2.00, 3.00)] and the sham one (t=4.50, P=0.382). Immunohistochemistry showed that the nestin+ cell density in the low-intensity group [(35.36±4.32) cell/mm2] and high-intensity group [(26.51±5.89) cell/mm2] were significantly lower than the sham group [(59.58±14.15) cell/mm2] (t=24.21, P=0.018; t=33.07, P=0.005); as for the mean absorbance of DCX+ cells, the low-intensity group (0.007±0.002) and the high-intensity group (0.006±0.002) were significantly lower than the sham group (0.011±0.001) (t=0.004, P=0.018; t=0.006, P=0.005); compared with the sham group [(1.13±0.14)×103 cell/mm2], the density of NeuN+ neurons in the high-intensity group [(0.75±0.08)×103 cell/mm2] was significantly reduced (t=0.38, P=0.017), and was not significantly changed in the low-intensity group [(0.88±0.19)×103 cell/mm2] (t=0.25, P=0.075). Western blotting results showed that, compared with the sham group, the expression levels of nestin, DCX, and NeuN were significantly reduced in the high-intensity group (t=0.74, P<0.001; t=0.18, P=0.014; t=0.35, P=0.008), but were not statistically changed in the low-intensity group (t=0.18, P=0.108; t=0.08, P=0.172; t=0.19, P=0.077). Conclusions: Pg injected through tail vein may reduce learning and memory abilities of wild-type rats, and may reduce the number of nestin, DCX, and NeuN-positive cells, and the protein expression levels of the above molecules in the hippocampus.

[Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer].

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.

[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

[A study on the identification of threshold for early warning on adverse weather events based on the association of apparent temperature and years of life lost].

Objective: To identify the threshold of a health warning system based on the association of apparent temperature and years of life lost (YLL). Methods: Daily mortality records and meteorological data were collected from 364 Chinese counties for 2006-2017. Distributed lag nonlinear model and multivariate Meta-analyses were applied to estimate the association between the apparent temperature and YLL rate. A regression tree model was employed to estimate the warning thresholds of the apparent temperature. Stratified analyses were further conducted by age and cause of death. Results: The daily YLL rate was 23.6/105. The mean daily apparent temperature was 15.7 ℃. U-shaped nonlinear associations were observed between apparent temperature and YLL rate. The actual temperature-caused YLL rate for the elderly was higher than the young population. The daily excess deaths rate increased with the higher effect levels. Conclusions: Regression tree model was employed to define the warning threshold for meteorological health risk. The present study provides theoretical support for the weather-related health warning system.

[Analysis of the effect of ipsilateral supraclavicular lymph node metastasis on the prognosis of N3 breast cancer].

Objective: The 6th edition American Joint Committee on Cancer (AJCC) staging system for breast cancer classifies ipsilateral supraclavicular lymph node metastasis (ISLM) downing stage from M1 to N3, suggesting more patients might receive radical treatment. The aim of this study was to analyze the effect of ISLM on the prognosis of N3 breast cancer and verify the rationality of modified staging. Methods: A total of 321 breast cancer patients with N3 according to the 6th edition AJCC staging system were retrospectively analyzed. Propensity Score Matching (PSM) was used to pair the different subgroups of N3. The primary end point was disease-free survival (DFS), the secondary end point was overall survival (OS). Kaplan-Meier method was used to calculate the DFS and OS. The differences between two groups were analyzed by the Log-rank test. Results: After PSM pairing twice, 78 patients with none-ISLM and 78 patients with ISLM were enrolled in the first group; 51 patients with none-ISLM was compared patients with isolated ISLM in the second group. The results of the two groups showed that patients with none-ISLM have a prolonged DFS (the first group: 58.9 months vs 32.1 months, P=0.101; the second group: 59.0 months vs 44.0 months, P=0.533), while the OS was opposite (the first group: 87.4 months vs 140.4 months, P=0.289; the second group: 87.4 months vs 137.1 months, P=0.289). Conclusions: The prognosis of breast cancer patients with ISLM is similar to that of patients with none-ISLM in stage N3. It is reasonable to include ISLM in N3 in the 6th edition AJCC staging system. Yet, prospective studies with larger sample size are needed to further confirmation.

[Significance of circulating tumor cell monitoring in targeted therapy for gastrointestinal stromal tumors].

Objective: To explore the significance of circulating tumor cell (CTC) monitoring in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST). Methods: A prospective cohort study was performed. The data of patients with locally advanced GIST or liver metastasis who were admitted to The Affiliated Hospital of Nantong University from August 2013 to December 2018 were collected. Inclusion criteria: (1) patients aged older than 18 years; (2) patients who were diagnosed with GIST based on pathology; (3) patients without surgery, whose preoperative imaging evaluation of GIST found the violations of the surrounding organs or partial transfer of an estimated difficulty to achieve R0 resection, or the maximum diameter of the tumor > 10 cm, or the liver metastasis, or the expectation of higher risk of surgical complications; (4) patients who were treated with the imatinib 400 mg/d for the first time; (5) Eastern Cooperative Oncology Group (ECOG) score of 0-2. Exclusion criteria: (1) genetic testing revealed a D842V mutation in exon 18 of the PDGFRA gene; (2) alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the normal upper limit; (3) serum total bilirubin >1.5 times of normal upper limit; (4) neutrophil count < 1.5×10(9)/L, or platelet count < 75×10(9)/L, or hemoglobin < 60 g/L; (5) creatinine > normal upper limit; (6) patients had serious cardiovascular and cerebrovascular diseases within 12 months before enrollment; (7) female patients were pregnant or lactating; (8) patients suffered from other serious acute and chronic physical or mental problems, and were not suitable for participating in this study judged by researchers. The patients who could not tolerate treatment regimen, or developed serious adverse reactions and did not follow the medication scheme after enrollment were excluded. Before imatinib treatment and 1-month and 2-month after treatment, quantitative PCR was used to detect the DOG-1 expression of monocytes in peripheral blood, and the ratio of DOG-1/ß-actin > 3×10(-5) was used as the CTC positive threshold of GIST. The positive rate of CTC, the efficacy of imatinib treatment (complete response, partial response, stable disease, progressive disease, and occurrence of adverse reactions), and the relationship between CTC positive rate and clinicopathological characteristics of patients were analyzed. Furthermore, the ratio of DOG-1 decrease/baseline DOG-1 after 1-month of treatment was used as an indicator to evaluate whether targeted therapy was effective. The receiver operating characteristic (ROC) curve was rendered, and the area under the curve (AUC) was calculated. Results: A total of 68 GIST patients were enrolled in this study, including 39 cases of locally advanced GIST and 29 cases with liver metastases, 32 males and 36 females with the mean age of (51.2±11.8) (range 31 to 74) years. After 2-month of imatinib treatment, 43 cases were evaluated as partial response, 11 cases as stable disease, and 14 cases as progressive disease, with an effective rate of 79.4% (54/68). During the treatment of imatinib, the incidence of grade 3 or higher adverse reactions was 22.1% (15/68), including 12 cases of grade 3 neutropenia and 3 of grade 4 drug eruption, which were all relieved after conservative treatment. The positive rates of CTC in 68 patients before treatment, 1-month and 2-month after treatment were 66.2% (45/68), 41.2% (28/68) and 23.5% (16/68), respectively. The positive rate of CTC was associated with tumor size, liver metastasis, mitotic count and risk level (all P<0.05). By analyzing the effective group and the ineffective group of targeted therapy, it was found that the positive rate of CTC in the effective group showed a decreasing trend, while the positive rate of CTC in the ineffective group showed an increasing trend. The AUC of predicting the efficacy of targeted therapy for GIST was 0.823 by detecting the change trend of CTC 1-month after treatment (P<0.001). When the DOG-1 content decreased by more than 57.5% 1-month after treatment, it can be used as an indicator to judge the effectiveness of the treatment, whose sensitivity was 72.2% and specificity was 100%. Conclusion: The detection of peripheral blood CTC can evaluate the efficacy of targeted therapy in GIST patients and can provide decision-making basis for further clinical treatment.

[The relationship between inflammatory factors and depression and its mechanism exploration].

Depression is a common and recurrent mental disease, with complex etiology, which is mainly affected by genetic, metabolic and social factors. The specific pathogenesis is still unclear. In recent years, the hypothesis of inflammatory factors related to depression has attracted wide attention of researchers. A large number of clinical experimental studies have shown that depression is related to the increase of proinflammatory factors in central and peripheral blood. The inflammatory factors in peripheral blood can spread in the brain through the way of specific transporters across the blood-brain barrier, and activate or participate in the brain inflammatory response, and ultimately affect the neuronal activity and neurotransmitter release in the emotional regulation area of the brain, which in turn leads to depressive symptoms. This paper summarizes the relationship between inflammatory factors and depression and its possible mechanism, which provides reference for further prevention and control, clinical treatment and scientific research of depression.