Primary drug resistance among HIV-1 patients in Hubei Province in 2020-2022 / 公共卫生与预防医学

Objective To investigate the prevalence of primary drug resistance among HIV-1 patients in Hubei Province from 2020 to 2022, and to provide corresponding basis and data support for HIV antiviral therapy (ART) in Hubei Province. Methods During 2020-2022, plasma samples of HIV-1 infected patients before ART were collected., Patients’ demographic data and baseline laboratory test data were also collected. HIV-1 pol region was amplified by in-house method for sub-type typing and drug-resistant mutation site analysis. Results The pol gene sequence was successfully amplified in 242 of 285 cases, with a success rate of 84.9%. CRF07_BC was the predominant HIV-1 sub-type, accounting for 47.11% (114/242), followed by CRF01_AE, accounting for 25.21% (61/242), sub-type B, accounting for 14.16% (35/242), and CRF55_01B, accounting for 4.13% (10/242). The primary resistance rate was 6.20% (15/242). The mutation site of nucleoside reverse transcriptase inhibitors (NRTIs) was mainly M184V, and the mutation sites of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were mainly E138A/G/EG and V179E. These different mutation sites led to different degrees of drug resistance to 12 drugs. The incidence of drug resistance mutation of CRF55_01B sub-type was significantly higher than that of other sub-types. Conclusion The primary drug resistance rate of HIV-1 infected patients is at a slightly high level in Hubei Province, and close monitoring of primary drug resistance and mutation sites should be strengthened before ART, especially for CRF55_01B sub-type.

Effect of fluoxetine combined with Shugan Jieyu capsule in the treatment of patients with depression and its impact on heart rate variability / 四川精神卫生

BackgroundDepression is a kind of disease with relatively high suicide risk， which seriously affects the quality of life of patients and their families， and brings a great burden to society. Antidepressants in western medicine are effective， but the improvement of depressive symptoms is relatively limited by single use， and the combination of two antidepressants may increase the risk of adverse reactions in patients. The rational use of Chinese patent medicine and western medicine may play a complementary role， and the safety of Chinese patent medicine is high. ObjectiveTo explore the early clinical efficacy of fluoxetine combined with Shugan Jieyu capsule in the treatment of depression， and to compare the differences in efficacy， safety and influence on heart rate variability between fluoxetine combined with Shugan Jieyu capsule and fluoxetine alone， so as to provide references for clinical medication of depression patients. MethodsFrom December 2015 to June 2016， 64 patients who met the diagnostic criteria of depression in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） who were hospitalized in the Second Affiliated Hospital of Xinxiang Medical University were selected as the research objects， and were randomly divided into the combined medication group and the fluoxetine group with 32 patients in each group. Patients in both groups were treated with fluoxetine， while patients in the combined medication group were treated with Shugan Jieyu capsule on this basis. Patients in both groups were assessed with Hamilton Depression Scale-24 item （HAMD-24）， Hamilton Anxiety Scale （HAMA） and Heart Rate Variability （HRV） before treatment， and were assessed with HAMD-24 and Treatment Emergent Symptom Scale （TESS） at the end of the 2nd， 4th and 6th week of treatment， and HRV was analyzed again at the end of the 6th week of treatment. ResultsThe study ultimately included 60 patients with depression， with 30 cases in the combination therapy group and 30 cases in the fluoxetine group. At the end of the 2nd， 4th and 6th week of treatment， the HAMD-24 score of the combined drug group was lower than that of the fluoxetine group （t=-2.677， -3.960， -4.432， P<0.05 or 0.01）. Compared with before treatment， the 24-hour mean standard deviation of normal RR intervals （SDNN）， normal low frequency （nLF） and normal high frequency （nHF） in the combined treatment group were higher at the end of the 6th week （t=-73.970， -31.878， -38.721， P<0.01）， but significant lower in LF/HF （t=3.525， P<0.01）. At the end of the 6th week of treatment， the total effective rate of the combined treatment group was higher than that of fluoxetine group， and the difference was statistically significant （86.67% vs. 70.00%， χ2=18.764， P<0.01）. At the 2nd， 4th and 6th week of treatment， there was no significant difference in the number of adverse reactions between the two groups （P>0.05）. ConclusionCompared with fluoxetine alone， Shugan Jieyu capsule combined with fluoxetine may be better in clinical efficacy and improvement of heart rate variability in patients with depression， without increasing adverse reactions.

The value of exhaled nitric oxide in assessing the risk of acute exacerbation and guiding the use of ICS in patients with COPD / 中国医师杂志

Objective:To explore the predictive value of exhaled nitric oxide (FeNO) for the risk of acute exacerbation in stable chronic obstructive pulmonary disease (COPD) patients over the next year and evaluate whether it can guide the use of inhaled corticosteroids (ICS).Methods:This study was a multicenter, retrospective and observational cohort study. The subjects of this study were stable COPD patients who were hospitalized in 12 hospitals in Hunan Province and Guangxi from January 2017 to December 2021. The patient′s basic Demography information, previous acute exacerbation history, pulmonary function, FeNO, chronic obstructive pulmonary disease assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score, chronic obstructive pulmonary disease control questionnaire (CCQ) score, and detailed treatment plan were collected. Based on FeNO 25 ppb, patients were divided into a high FeNO group and a normal FeNO group. All patients were followed up for 1 year and information on acute exacerbation was recorded.Results:A total of 825 patients were included, aged (63.5±9.1)years, with a median of 25 ppb of FeNO. A number of 825 patients were followed up for 1 year, of which 262(31.8%) experienced acute exacerbation. Multivariate logistic regression found that FeNO, CAT score, smoking cessation, and past history of acute exacerbation were independent factors predicting acute exacerbation in COPD patients in the next year (all P<0.05). High FeNO was a protective factor for acute exacerbation in COPD patients in the next year, with an OR value of 0.10 ( P<0.001). Further analysis found that the proportion of patients in the high FeNO group using ICS was significantly higher than that in the normal FeNO group [58.8%(247/420) vs 48.6%(197/405), P=0.003]. In the high FeNO group, using ICS can reduce the incidence of acute exacerbation of COPD in the next year [8.9%(22/247) vs 15.6%(27/173), P<0.05], while in the normal FeNO group, there was no statistically significant difference in the frequency of acute exacerbation between patients using ICS and those not using ICS ( P>0.05). Conclusions:FeNO is an independent factor predicting the acute exacerbation of COPD in the next year, and patients with high FeNO levels may consider using ICS in combination.

Related factors of acute exacerbation of chronic obstructive pulmonary disease and the value of inhaled glucocorticoid guided by eosinophil in peripheral blood / 中国医师杂志

Objective:To explore the risk factors of acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) and whether Eosinophil (EOS) in peripheral blood can guide the treatment of inhaled corticosteroids (ICS).Methods:This study was a single center, Prospective cohort study. The subjects of this study were from stable COPD patients who were treated in the Department of Respiratory Medicine of the Xiangya Second Hospital of Central South University from January 2020 to December 2021. Patient general information, past year AE status, exposure risk factors, modified version of the British Medical Research Council Respiratory Difficulty Questionnaire (mMRC) score, Chronic Obstructive Pulmonary Disease Assessment Questionnaire (CAT) score, ICS usage, lung function, blood routine, etc. were collected. We followed up the patient for one year. During the follow-up period, the clinical characteristics of patients with and without AE were compared to analyze the correlation between blood EOS and ICS use.Results:The median blood EOS of 617 stable COPD patients was 0.13×10 9/L, 289 patients (46.8%) with chronic obstructive pulmonary disease had a history of AE, and 207 patients (33.5%) experienced AE during 1-year follow-up. The results of univariate analysis showed that the future occurrence of AE in COPD was correlated with body mass index (BMI), AE history, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, GOLD grouping, mMRC score, and CAT score (all P<0.05). The results of logistic multiple factor regression analysis showed that patients with BMI<24 kg/m 2, AE in the past year, severe AE in the past year, smoking history and other exposure factors, GOLD level 2 or above, GOLD C and D groups, and mMRC score≥ 2 had a higher risk of future AE (all P<0.05). There was no statistically significant difference in the incidence of AE between patients with COPD with different levels of EOS and those without ICS during a 1-year follow-up period (all P>0.05). Conclusions:The past 1-year AE history, BMI, exposure risk factors, degree of airflow restriction, and respiratory symptoms of patients with chronic obstructive pulmonary disease can predict future AE risk. There is no significant difference in future AE risk among patients with different levels of EOS, and EOS cannot guide ICS treatment to reduce AE risk.

Symptom scores of patients with chronic obstructive pulmonary disease and their response to different inhalation drug treatments / 中国医师杂志

Objective:To analyze the response of patients with chronic obstructive pulmonary disease (COPD) with multiple and few symptoms to different inhalation drugs, including acute exacerbation and symptom changes.Methods:This study was a multi center, retrospective Cohort study. The subjects of this study were patients with chronic obstructive pulmonary disease in stable stage in 12 hospitals in Hunan and Guangxi from December 2016 to February 2022. Demographics data, lung function, Chronic Obstructive Pulmonary Disease Assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score and inhalation drug scheme of patients were collected. According to the CAT and mMRC scores, patients were divided into a multi symptom group (CAT≥10 points or mMRC≥2 points) or a few symptom group (CAT<10 points and mMRC<1 point); Subsequently, they were divided into four subgroups based on the inhalation drug regimen: long-acting anticholinergic drugs (LAMA) group, long-acting β2-receptor agonists (LABA)+ inhaled corticosteroids (ICS) group, LABA+ LAMA group, and LABA+ LAMA+ ICS group. All patients were followed up for 1 year, with minimum clinical improvement (MCID) defined as a decrease of ≥2 points in the patient′s CAT score at 6 months, and clinical symptom deterioration (CSD) defined as an increase of ≥2 points in the patient′s CAT score at 6 months.Results:A total of 929 patients with chronic obstructive pulmonary disease were included, including 719(77.4%) with multiple symptoms and 210(22.6%) with few symptoms. There was no statistically significant difference in MCID, CSD, acute exacerbation, hospitalization frequency, and mortality rate among subgroups of asymptomatic COPD patients treated with different inhalation drug regimens (all P>0.05). Among patients with multiple symptoms of chronic obstructive pulmonary disease, compared to those who use LAMA or LABA+ ICS, those who used LABA+ LAMA or LABA+ LAMA+ ICS were more likely to obtain MCID and had a more significant improvement in CAT scores, and the risk of acute exacerbation is lower (all P<0.05). Conclusions:Lesser symptomatic COPD patients should receive single drug LAMA as the initial inhalation treatment drug, while multi symptomatic COPD patients should receive LABA+ LAMA as the initial inhalation treatment drug.

Precision medicine in chronic obstructive pulmonary disease / 中国医师杂志

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous chronic Respiratory disease. In the past 20 years, precision medicine has gradually integrated into the management of COPD. At present, individualized treatment is mainly based on its symptoms, acute exacerbation risk and eosinophil count. In the future, with the development of risk factors and their pathophysiology, quantitative imaging technology, biomarkers and gene analysis, precision medicine will have further development in the management of COPD treatment.

Study on molecular mechanism of Jichuanjian improving Yang deficiency constipation based on Ca / 中国药理学通报

Aim To investigate the effect of JiChuanjian(JCJ)on the Yang deficiency constipation based on Ca

Progress and future perspective of epidemiological research of air pollution and climate change in the context of achieving carbon peaking and carbon neutrality goals / 中华流行病学杂志

Climate change is the great health challenge for human beings in the 21st century. Air pollution is also an important public health problem worldwide. China announced the climate commitment to achieve carbon peaking by 2030 and carbon neutrality by 2060. Achieving these goals would not only have far-reaching effects on air pollution control and climate change, but also improve the population health in China. Air pollution and climate change epidemiology are important aspects of environmental epidemiology. In this paper, we discuss the current status and future development of epidemiological research of air pollution and climate change in the context of achieving carbon peaking and carbon neutrality goals to provide ideas and suggestions for environmental and health studies in the future.

Quality Difference Analysis of Raw and Steamed Products of Citri Reticulatae Pericarpium Based on Electronic Eye Technique and Chemical Fingerprint / 中国实验方剂学杂志

ObjectiveTo explore the quality differences between steamed products and raw products of Citri Reticulatae Pericarpium（CRP）. MethodThe color of steamed products and raw products of CRP was determined from the perspective of appearance by electronic eye technique， and the quality differences between them was objectively characterized by the luminous value（L*）， yellow-blue value（b*）， red-green value（a*） and total chromatic value（E*ab）. Based on this， ultra-high performance liquid chromatography（UPLC） was used to establish a fingerprint evaluation method with the mobile phase of acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-5 min， 5%A； 5-30 min， 5%-20%A； 30-60 min， 20%-52%A）， detection wavelength at 270 nm， flow rate of 0.3 mL·min-1 and column temperature of 30 ℃. The quality differences between steamed products and raw products of CRP were compared from the perspective of chemical composition， and correlation analysis was used to reveal the correlation between the difference in appearance color and the difference in internal chemical composition. ResultAfter being steamed， L*， b* and E*ab of CRP showed an overall decreasing trend， indicating that the color of the steamed products darkened and deepened from yellow to blue but still tended to be yellow， while a* showed an overall increasing trend， indicating that the color of the steamed products tended to red. A total of 24 peaks were identified in the fingerprint profiles of raw products and steamed products of CRP， and 13 of the main peaks were identified. The precision， stability and repeatability studies showed that compared with the reference peak （peak 14， hesperidin）， the relative standard deviations（RSDs） of the relative peak area and relative retention time of the remaining peaks were<3.0%.The results of chemometric statistical analysis showed that there were some differences between raw products and steamed products of CRP， and 7 main differential components were identified， among which 5-hydroxymaltol（peak 1） and 5-hydroxymethylfurfural（peak 2） were the characteristic components of steamed products. The correlation analysis results showed that， in addition to the above two characteristic components， four components of peak 4， peak 10 （vicenin-2）， peak 23 （tangeretin） and peak 24 （5-demethylnobiletin） also correlated significantly with the color change （E*ab） of the samples （P<0.05， P<0.01）. ConclusionBefore and after steaming， not only the chemical composition changes， but also the color. Comparing the characteristic peaks of chemical composition difference and color difference before and after steaming of CRP， it is found that 5-hydroxymaltol， 5-hydroxymethylfurfural and peak 4 are common characteristic difference components， which can provide a reference for establishing the characteristic quality control method of steamed products， and quickly evaluating the quality difference between raw products and steamed products of CRP.

Bavachin induces apoptosis in colorectal cancer cells through Gadd45a via the MAPK signaling pathway / 中国天然药物

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.

Relationship between inducible nitric oxide synthase and delayed encephalopathy in carbon monoxide poisoning / 中华急诊医学杂志

Objective:To observe the relationship between inducible carbon monoxide synthase (iNOS) and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), and explore its mechanism of action in DEACMP.Methods:This study was designed as prospective cohort study. Patients with acute carbon monoxide poisoning who met the diagnostic criteria and were admitted to Emergency Intensive Care Unit(EICU) of our hospital from June 2019 to June 2021 were selected as subjects. Patients were divided into the DEACMP group and non-DEACMP group according to the occurrence of DEACMP. Serum samples were collected on the first 24 h after admission and on day 7 and 14 after admission, and the serum nitric oxide (NO), neuronal nitric oxide synthase (nNOS), inducible carbon monoxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) level were measured by enzyme-linked immunosorbent assay. The generalized estimating equation was used to estimate the difference of NO, nNOS, iNOS and eNOS between DEACMP and non-DEACMP patients.Results:A total of 78 patients with carbon monoxide poisoning were included in our study finally, including 49 (62.82%) males and 29 (37.18%) females, with an average age of (53.96±14.95) years, 20 (25.64%) patients with DEACMP, and 1 (1.28%) death. Univariate analysis showed that patients with DEACMP had an average increase of 3 h (95% CI: 1.00, 5.00) in carbon monoxide exposure time and a 5-point decrease in GCS score (95% CI: 1.00, 6.00) than the patients without DEACMP, and the proportion of patients with severe carbon monoxide poisoning in the DEACMP group was higher than that of the non-DEACMP group (90.00% vs. 32.76%). According to the analysis of generalized estimation equation, on day 7 and 14 after admission, Compared with non-DEACMP patients, neither by performing unadjusted nor adjusted analysis with the iNOS of DEACMP patients was significantly higher than that in non-DEACMP patients regardless of whether exposure time, GCS score, coma time or severity of carbon monoxide poisoning were adjusted or not ( P <0.01 or P <0.05). Except for the level of nNOS in the GEE model adjusted with carbon monoxide exposure time, the levels of NO, nNOS and eNOS showed no significant difference between DEACMP and non-DEACMP patients ( P >0.05). Conclusions:The expression of iNOS level is increased in DEACMP patients, and its continuous expression may be involved in the pathogenesis of DEACMP.

Distribution characteristics of gene mutations in patients with acute myeloid leukemia and their relationship with prognosis / 白血病·淋巴瘤

Objective:To investigate the distribution characteristics of gene mutations and their relationship with prognosis in newly diagnosed patients with acute myeloid leukemia (AML).Methods:The clinical data of 225 newly diagnosed AML (non-acute promyelocytic leukemia) patients in the Second Affiliated Hospital (Tangdu Hospital) of Air Force Medical University from May 2016 to December 2019 were retrospectively analyzed. Thirty-four gene mutations related to AML, myelodyplastic syndrome (MDS) and myeloproliterative neoplasms (MPN) were detected by second-generation sequencing. The distribution of all gene mutations and its difference among different age groups were analyzed, and the differences in survival of patients with different gene mutations were compared. The Cox regression model was employed to analyze the survival influencing factors of patients aged <60 years old and ≥60 years old.Results:A total of 496 gene mutation sites were detected in 225 patients, with a median variant allel frequency (VAF) of 38.55% (1.00%-94.86%) and a median gene mutations of 3/case (0-8/case). The genes with high mutation frequency were ASXL1, CEBPA, NPM1, NRAS, FLT3-ITD, DNMT3A, IDH2, TET2, RUNX1, and IDH1. The gene mutation rates of TET2, SRSF2 and SF3B1 in patients aged ≥60 years old (56 cases) were higher than those in patients aged <60 years old (169 cases), and the differences were statistically significant (all P < 0.01). The proportion of patients aged ≥60 years old with 3 or more gene mutations was higher than that of patients aged <60 years old [53.6% (30/56) vs. 33.1% (56/169), χ2 = 7.44, P = 0.006]. The overall survival (OS) of patients with TP53, RUNX1 or FLT3-ITD gene mutation was worse than that of wild-type patients, the OS of patients with CEBPA double mutations was better than that of patients with CEBPA single mutation or wild-type, and the differences were statistically significant (all P < 0.05). Multivariate Cox regression analysis showed that CEBPA ( HR = 0.279, 95% CI 0.084-0.926, P = 0.037), TET2 ( HR = 2.611, 95% CI 1.115-6.111, P = 0.027) and TP53 ( HR = 3.609, 95% CI 1.159-11.234, P = 0.027) gene mutations were independent factors affecting the survival of AML patients aged <60 years old, ASXL1 ( HR = 3.523, 95% CI 1.385-8.962, P = 0.008), FLT3-ITD ( HR = 4.618, 95% CI 1.813-11.762, P = 0.001) and NRAS ( HR = 2.896, 95% CI 1.166-7.000, P = 0.022) were independent risk factors of the survival of AML patients aged ≥60 years old. Conclusions:There are differences in the distribution of gene mutations among AML patients with different age, and the elderly patients are more likely to have multiple gene mutations at the same time. In addition to the currently known CEBPA double mutations, TP53, ASXL1, RUNX1 and other gene mutations, TET2 and NRAS gene mutations may also be factors affecting the prognosis.

The osteogenic niche-targeted arsenic nanoparticles prevent colonization of disseminated breast tumor cells in the bone

Up to 70% of patients with late-stage breast cancer have bone metastasis. Current treatment regimens for breast cancer bone metastasis are palliative with no therapeutic cure. Disseminated tumor cells (DTCs) colonize inside the osteogenic niches in the early stage of bone metastasis. Drug delivery into osteogenic niches to inhibit DTC colonization can prevent bone metastasis from entering its late stage and therefore cure bone metastasis. Here, we constructed a 50% DSS6 peptide conjugated nanoparticle to target the osteogenic niche. The osteogenic niche was always located at the endosteum with immature hydroxyapatite. Arsenic-manganese nanocrystals (around 14 nm) were loaded in osteogenic niche-targeted PEG-PLGA nanoparticles with an acidic environment-triggered arsenic release. Arsenic formulations greatly reduced 4T1 cell adhesion to mesenchymal stem cells (MSCs)/preosteoblasts (pre-OBs) and osteogenic differentiation of osteoblastic cells. Arsenic formulations also prevented tumor cell colonization and dormancy via altering the direct interaction between 4T1 cells and MSCs/pre-OBs. The chemotactic migration of 4T1 cells toward osteogenic cells was blocked by arsenic in mimic 3D osteogenic niche. Systemic administration of osteogenic niche-targeted arsenic nanoparticles significantly extended the survival of mice with 4T1 syngeneic bone metastasis. Our findings provide an effective approach for osteogenic niche-specific drug delivery and suggest that bone metastasis can be effectively inhibited by blockage of tumor cell colonization in the bone microenvironment.

Effects of Notch1 signaling on regulatory T cells and coronary artery lesions in childhood Kawasaki disease / 中华风湿病学杂志

Objective:To explore the effect of Notch1 signaling on regulatory T cells and its roles in vascular damage in patients with Kawasaki disease (KD).Methods:A total of 42 children with KD were enrolled in the present study from March 2019 to June 2020, as 32 age-matched healthy children were recruited as control. The proportions of CD4 +CD25 hiFoxp 3+ regulatory T cells (Treg) and expressions of transcription factor forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte associated antigen-4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and Notch1 protein were evaluated by flow cytometry. Chromatin immunoprecipitation was conducted to detect acetylation level of histone H4 (H4Ac) associated with the promoter of Foxp3 gene and its binding abilities of Notch1 intracellular domain 1 (NICD1), recombination signal binding protein for immunoglobulin kappa J region (RBP-J) and p300 in CD4 + T cells. Transcription levels of Foxp3, presenilin 1 (PSEN1), mastermind like transcriptional coactivator 1 (MAML1), and RBP-J in CD4 + T cells were determined by real-time polymerase chain reaction (PCR). Concentrations of interleukin (IL)-10 and transforming growth factor-β (TGF-β) in plasma and culture supernatant stimulated with Jagged1 were measured by enzyme linked immunosorbent assay. Independent-sample t-test, Pearson correlation analysis was used as the statistical method in this study. Results:① The frequencies of Treg in acute KD patients decreased significantly [(4.3±1.5)% vs (7.9±2.9)%; t=6.41, P<0.001], as protein levels of Foxp3, CTLA4 and GITR and concentrations of IL-10 and TGF-β in plasma reduced remarkably in acute KD patients ( t=6.87, P<0.001; t=4.26, P<0.001; t=7.88, P<0.001; t=8.42, P<0.001; t=13.01, P<0.001). All parameters afore-mentioned in patients combined with coronary artery lesions (CAL) were lower than those of patients without coronary artery lesions (NCAL) ( t=5.83, P<0.001; t=3.83, P<0.001; t=3.28, P=0.002; t=5.05, P<0.001; t=5.96, P<0.001; t=5.17, P<0.001), and increased after therapy ( t=7.13, P<0.001; t=6.10, P<0.001; t=4.31, P<0.001; t=6.55, P<0.001; t=7.40, P<0.001; t=7.84, P<0.001). ② H4Ac associated with promoter of Foxp3 gene and the binding abilities of NICD1 and p300 in acute KD patients were lower than those of the controls ( t=10.25, P<0.001; t=6.93, P<0.001; t=6.75, P<0.001), and increased remarkably after therapy ( t=7.72, P<0.001; t=4.16, P<0.001; t=5.76, P<0.001). Meanwhile, the three items in CAL group were found to be less than those of NCAL group ( t=6.08, P<0.001; t=2.66, P=0.011; t=6.02, P<0.001). Pearson correlation analysis showed a positive correlation between H4Ac associated with Foxp3 promoter and its mRNA level in acute KD patients ( r=0.47, P<0.001). No statistical significant difference about the binding ability of RBP-J with Foxp3 promoter were found among the groups ( t=0.57, P>0.05; t=0.61, P>0.05; t=1.20, P>0.05). ③ Protein level of Notch1 and the expressions of PSEN1, MAML1 and RBP-J mRNA in CD4 + T cells from acute KD patients were down-regulated remarkably ( t=5.28, P<0.001; t=6.31, P<0.001; t=11.78, P<0.001; t=8.06, P<0.001), and restored after therapy ( t=4.77, P<0.001; t=6.43, P<0.001; t=11.95, P<0.001; t=7.79, P<0.001). In parallel, the four indexes aforementioned of CAL group were lower than those of NCAL group ( t=3.16, P=0.003; t=4.13, P<0.001; t=5.42, P<0.001; t=4.05, P<0.001). Upon rhJagged1 stimulation for 48 hours, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in CD4 + T cells in KD patients and control group was significantly higher than those of untreated group [(KD: t=15.36, P<0.001; t=7.25, P<0.001; t=14.29, P<0.001), (Ctrl: t=7.87, P<0.001; t=5.71, P<0.001; t=8.74, P<0.001)], as the binding ability of RBP-J with Foxp3 promoter increased slightly without statistically significant difference (KD: t=1.11, P>0.05; Ctrl: t=1.37, P>0.05). Simultaneously, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in KD group were still lower than those of the control group after stimulation ( t=3.86, P<0.001; t=3.42, P=0.001; t=2.85, P=0.006). ④ After incubation of PBMC from heathy children with KD serum, the proportion of Treg cells, protein level of Foxp3 and expressions of Notch1 and RBP-J in CD4 + T cells in the group treated with IVIG increased significantly compared with the untreated group ( t=7.10, P<0.001; t=10.16, P<0.001; t=8.06, P<0.001; t=9.77, P<0.001), as well as H4Ac level of Foxp3 promoter and its binding abilities with NICD1 in the group treat with IVIG were also higher than the latter ( t=7.24, P<0.001; t=8.24, P<0.001). Conclusion:Insufficiency and impaired function of Treg caused by aberrant Notch1 signaling may be the important factor contributing to immune dysfunction and vascular damage in KD.

Progress in arsenic carcinogenic signaling transduction pathway / 中华地方病学杂志

Arsenic, as a metal element, has metallic and non-metallic properties and is widely distributed in nature. In the list of carcinogens of the International Agency for Research on Cancer, arsenic is clearly listed as the first class of carcinogens. Chronic arsenic poisoning caused by arsenic contamination of drinking water is a major health problem facing human beings worldwide. This kind of pollution occurs naturally due to geological structure, and the most serious one can lead to cancer, among which skin cancer is the most specific. In addition, epidemiological studies have shown that long-term arsenic exposure can also lead to bladder cancer, lung cancer, and liver cancer, etc. However, there have been a number of different views on the potential mechanisms of arsenic carcinogenesis. Carcinogenesis through signal transduction pathway is one of the important molecular mechanisms, including Wnt, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K/AKT/mTOR), nuclear factor kappa-B (NF-κB) and transforming growth factor-β (TGF-β). When there is a problem in the upstream and downstream or one of its links in the signal transduction pathway, the proliferation and differentiation of human cells are out of control, which can lead to cancer.

Analysis of urinary arsenic methylation metabolites in population exposed to arsenic through drinking water before and after water improvement / 中华地方病学杂志

Objective:To study the effect of water improvement on urinary arsenic methylation metabolism in population exposed to arsenic through drinking water.Methods:A cluster sampling method was used to select drinking water type arsenism areas in Bayannur City, Inner Mongolia Autonomous Region. Permanent residents lived in the arsenism areas for more than 10 years were selected as the survey subjects. Urine samples ( n = 874, 111, 145) were collected in 2004 (before water improvement), 2014 (4 years after water improvement) and 2017 (7 years after water improvement), respectively, and some subjects were followed up in 2014 and 2017. High performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect different forms of arsenic metabolites in urine [inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA)], and total arsenic (tAs), the iAs percentage (iAs%), MMA percentage (MMA%), DMA percentage (DMA%), monomethylation rate (PMI), dimethylation rate (SMI), and the ratio of MMA to DMA (MMA/DMA) were calculated. The content and distribution of urinary arsenic metabolites in people exposed to arsenic before and after water improvement were compared and analyzed. Results:Compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine of arsenic exposed population in 2014 were lower ( Z =-14.12,-12.79,-14.27,-14.21,-6.90, P < 0.001), the levels of MMA%, DMA% and PMI were higher ( Z =-3.22,-2.91,-6.90, P < 0.05); in the same drinking water arsenic exposed population, compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine ( n = 48) were lower ( Z =-5.57,-5.53,-5.54,-5.55,-2.86, P < 0.05) in 2014, and PMI level was higher ( Z =-2.86, P = 0.004). Compared with 2014, the levels of iAs% and MMA/DMA in urine of arsenic exposed population in 2017 were lower ( Z =-4.97,-2.25, P < 0.05), the levels of MMA, DMA, tAs, DMA%, PMI and SMI were higher ( Z =-4.01,-5.39,-4.77,-4.61,-4.97,-2.25, P < 0.05); in the same drinking water arsenic exposed population, compared with 2014, the level of iAs% in urine ( n = 28) was lower ( Z =-2.87, P = 0.004) in 2017, the levels of DMA% and PMI were higher ( Z =-2.32,-2.87, P < 0.05). Conclusion:Water improvement could significantly reduce the levels of urinary arsenic metabolites iAs, MMA, DMA and tAs and increase the level of DMA% in arsenic exposed population.

The biological activity of prodigiosin on adriamycin-resistant breast cancer cells in vitro / 中国药理学通报

Aim To investigate the effect of prodigiosin on the proliferation, migration, cell cycle and apopto- sis of adriamycin-resistant breast cancer cell line MCF- 7/ADR.Methods CCK-8, colony formation assay, scratch test and Transwell were used to detect the pro¬liferation and migration of MCF-7/ADR after treatment with different concentrations of prodigiosin.How cy¬tometry and DAP1 staining were used to detect the cell cycle and apoptosis of MCF-7/ADR cell line after treatment with different concentrations of prodigiosin.Western blot was used to detect the effect of prodigiosin on the expression of caspase-3, Bax and Bcl-2 in MCF- 7/ADR cells.Results Prodigiosin inhibited the pro¬liferation and migration of MCF-7/ADR cell line in a concentration- and time-dependent manner ( P <0.05 ).In addition, prodigiosin enhanced the in¬hibitor}' effect of adriamycin on MCF-7/ADR cell line.Prodigiosin arrested MCF-7/ADR cell line cycle in the S phase and induced cell apoptosis in a time- and dose- dependent manner.The percentage of S phase cells treated with 2 mg • L 1 prodigiosin for 48 hours in¬creased to 35.3% , and the apoptotic rate was as high as 64.83% , which were statistically significant com¬pared with the control group ( P < 0.05 ).Prodigiosin could up-regulate the expression of apoptosis protein caspase-3 and Bax and inhibit the expression of Bcl-2 protein in MCF-7/ADK cell.Conclusions Prodigio¬sin can effectively inhibit the proliferation, migration and promote cell apoptosis and regulate cell cycle in adriamvcin-resistant breast cancer cell line MCF-7/ ADR.Prodigiosin can enhance the sensitivity of MCF- 7/ADR cell line to adriamycin.

Application of LAg-avidity EIA in the estimate of HIV-1 incidence among key surveillance populations in Hubei Province / 公共卫生与预防医学

Objective Limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA) was applied to calculate the HIV-1 incidence of new HIV infections among men who have sex with men(MSM), drug users(DUS), female sex workers(FSW) and male patients in sexually transmitted diseases clinics(STD) in 2017-2020 of Hubei. Methods HIV-1 antibody positive samples were collected from four key groups in the national HIV sentinel surveillance from 2017 to 2020, and tested by the LAg-Avidity EIA to estimate the annual new infection rate of each group. Results The prevalence of MSM was 2.90%, 4.48%, 3.63 and 2.78% from 2017-2020, respectively, which was the highest among the four groups. The rate of late diagnosis increased from 16.67% in 2017 to 28.81% in 2020.The incidence of MSM was 1.64%(0.85%-2.44%),1.41%(0.59%-2.23%),1.46% (0.71%-2.21%) and 0.96%(0.34%-1.57%), respectively, and the difference was not statistically significant (χ2=1.491, P=0.684). The prevalence of STD from 2017-2020 was 0.03%, 0.01%, 0.06% and 0.08%, respectively, with the incidence was 0.09% (-0.06%-0.25%), 0.10(-0.06%-0.26%), 0.26% (0.02%-0.50%) and 0.04%(-0.07%-0.15%). The prevalence and incidence among FSW remains very low, while the prevalence of DUS fluctuated slightly, but no new infections have been detected. Conclusion The incidence of new HIV infection among MSM in Hubei province from 2017-2020 is relatively high compared with other key groups, but the overall trend is declining, thus the intervention of MSM should be further strengthened and expand the coverage of testing in key populations.

Changes and significance of CD8 + CD28 - regulatory T cells in acute phase of Kawasaki disease / 中华微生物学和免疫学杂志

Objective:To investigate the changes of CD8 + CD28 - regulatory T cells (Treg) and its role in the pathogenesis of Kawasaki disease (KD). Methods:A total of 48 children with KD were enrolled in the present study from June 2019 to December 2021. Blood samples were collected from them during acute phage of KD and after intravenous immunoglobulin (IVIG) treatment. Another 32 age-matched healthy children were recruited as control group. The proportions of CD8 + CD28 -Treg cells and the expression of programmed cell death protein 1 (PD-1), factor associated suicide ligand (FasL), inducible T-cell co-stimulator ligand (ICOSL), CD80 and CD86 protein were evaluated by flow cytometry. The expression of Helios, perforin, granzyme B, immunoglobulin-like transcript 3 (ILT3) and ILT4 at the transcription level was measured by real-time PCR. Concentrations of IL-10 and TGF-β in the culture supernatants of CD8 + CD28 -Treg cells stimulated with activated CD4 + T cells were measured by ELISA. Results:⑴ The proportions of CD8 + CD28 -Treg cells and the expression of Helios in patients with acute KD were higher than those in the control group ( P<0.05), and reduced remarkably after IVIG therapy ( P<0.05). The two afore-mentioned indexes were lower in patients combined with coronary artery lesion (CAL) than in those without coronary artery lesion (NCAL) ( P<0.05). ⑵ Compared with the control group, the patients with acute KD showed increased expression of FasL, PD-1, ICOSL and perforin in CD8 + CD28 -Treg cells ( P<0.05). The concentrations of IL-10 and TGF-β1 in the culture supernatants of CD8 + CD28 -Treg cells from patients with acute KD were lower than those in the control group after stimulation with activated CD4 + T cells ( P<0.05), which restored to some extent after IVIG treatment ( P<0.05). All of the six above-mentioned indexes in the CAL group were found to be lower than those in the NCAL group ( P<0.05). There were slight differences in granzyme B expression between different groups ( P>0.05). (3) In comparison with the healthy controls, the patients with acute KD showed overexpressed co-stimulatory molecules such as CD80 and CD86 on CD14 + cells ( P<0.05) and up-regulated expression of inhibitory molecules ILT3 and ILT4 ( P<0.05), which were restored remarkably after IVIG treatment ( P<0.05). Furthermore, the expression of CD80 and CD86 at protein level increased in the CAL group than in the NCAL group ( P<0.05), while the expression of ILT3 and ILT4 at transcriptional level decreased in the CAL group ( P<0.05). Conclusions:Relative insufficiency and impaired function of CD8 + CD28 -Treg cells might be one of the important factors resulting in immune dysfunction and vascular damage in KD patients.

Changes and significance of granulocyte-like myeloid-derived suppressor cells during acute phase of Kawasaki disease / 中华微生物学和免疫学杂志

Objective:To investigate the changes and significance of granulocyte-like myeloid-derived suppressor cells (G-MDSC) in the acute phage of Kawasaki disease (KD).Methods:Forty-two children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC, the concentration of reactive oxygen species (ROS) and the expression of arginase-1 (Arg-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte associated protein 4 (CTLA4), glycoprotein 130 (gp130) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) at protein level were detected by flow cytometry. Quantitative real-time PCR was used to measure the expression of inducible nitric oxide synthase (iNOS), interferon regulatory factor 8 (IRF-8), IL-6 receptor α subunit (IL-6Rα), granulocyte colony-stimulating factor receptor (G-CSFR), CCAAT/enhancer binding protein β (C/EBPβ), suppressor of cytokine signaling 1 (SOCS1) and SOCS3 at mRNA level in G-MDSC. Chromatin immunoprecipitation was performed to detect the acetylation of histone H3 at the promoters of SOCS1 and SOCS3 genes. Plasma concentrations of IL-6 and granulocyte colony-stimulating factor (G-CSF) and protein levels of IL-10, transforming growth factor-β (TGF-β) and nitric oxide (NO) in the culture supernatant of G-MDSC stimulated with LPS were measured by ELISA. Results:(1) Compared with the control group, the proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC as well as the concentration of ROS and the expression of inhibitory molecules (Arg-1, PD-L1 and CTLA4) in G-MDSC increased significantly in patients with acute KD ( P<0.05). Moreover, the concentrations of IL-10 and TGF-β in culture supernatant of G-MDSC were also higher than those of the control group after stimulation with lipopolysaccharide for 48 h ( P<0.05). All of the seven afore-mentioned indexes in KD patients with coronary artery lesion (CAL group ) were lower than those in patients without coronary artery lesion (NCAL group) ( P<0.05), and restored to some extent after IVIG therapy ( P<0.05). There were no statistical differences in iNOS expression or NO concentration in culture supernatant of G-MDSC among different groups ( P<0.05). (2) Plasma concentrations of IL-6 and G-CSF, and the expression of IL-6Rα, gp130, G-CSFR, pSTAT3 and C/EBPβ increased remarkably during acute phase of KD ( P<0.05). The expression of IRF-8 at transcription level in patients with acute KD was found to be lower than that of healthy controls ( P<0.05), and restored significantly after IVIG therapy ( P<0.05). Moreover, the plasma concentrations of IL-6 and G-CSF and the expression of IL-6Rα, gp130, G-CSFR and IRF-8 in the CAL group were higher than those in the NCAL group ( P<0.05), while the expression of pSTAT3 and C/EBPβ was lower in the CAL group ( P<0.05), which were restored by IVIG therapy ( P<0.05). (3) In patients with acute KD, the expression of SOCS1 and SOCS3 at mRNA level and histone acetylation at the promoters of SOCS1 and SOCS3 genes were reduced significantly in comparison with those in healthy controls ( P<0.05) , but were increased remarkably after IVIG treatment( P<0.05). The four indexes were higher in the CAL group than in the NCAL group ( P<0.05). Pearson correlation analysis showed the expression of SOCS1 and SOCS3 was negatively correlated with the protein level of pSTAT3 in G-MDSC of patients with acute KD ( r=-0.46 and -0.32, P<0.05). Conclusions:Changes in the number and function of G-MDSC caused by aberrant histone acetylation at SOCS1 and SOCS3 genes might contribute to the immune dysfunction and vascular damage in patients with KD.