Objective:To analyze the epidemiological characteristics and trend of hospitalization of the patients with herpes zoster in Beijing from 2017 to 2022.Methods:In this retrospective study, the information of hospitalization of herpes zoster patients were collected from all medical institutions at the first level and above in Xicheng, Changping, and Miyun districts of Beijing. The age and gender specific hospitalization rates and age-standardized hospitalization rates were calculated. Joinpoint regression model was used to explore the trend of the hospitalization rates, and the influencing factors of the hospital stay length and complications were analyzed.Results:The age-standardized hospitalization rate of the patients with herpes zoster was 10.82/100 000-18.43/100 000 in Beijing from 2017 to 2022 [annual percent change (APC) =5.86%, 95% CI: -2.80%-15.98%]. The age-standardized hospitalization rate of the cases with herpes zoster as the main diagnosis showed an upward trend (APC=11.35%, 95% CI: 7.21%-16.23%). The age-standardized hospitalization rate showed an upward trend in women (APC=14.34%, 95% CI: 7.95%-22.37%). The hospitalization rate showed a downward trend in age group 30-39 years (APC=-24.92%, 95% CI: -48.56% - -1.85%) and showed upward trends in age group 70-79 years and 80-109 years (APC=23.18%, 95% CI: 13.53%-35.58%; APC=4.90%, 95% CI: 1.18%-9.19%). Complications occurred in 66.28% (680/1 026) of the patients. The median hospital stay length was 9 (5,15) days, and the patients with high age (≥80 years) and two or more complications had longer hospital stay, which were 12 (6, 23) and 14 (7, 27) days respectively ( P<0.001). Conclusions:The hospitalization rate in women and the elderly aged ≥70 years with herpes zoster as the main diagnosis showed upward trends in Beijing in recent years. The elderly aged ≥80 years usually had longer hospital stay, showing a relatively disease burden level. More attention should be paid to development of intervention strategies, such as vaccine, for this population.

Objective:To analyze the epidemiological characteristics and trend of hospitalization of the patients with herpes zoster in Beijing from 2017 to 2022.Methods:In this retrospective study, the information of hospitalization of herpes zoster patients were collected from all medical institutions at the first level and above in Xicheng, Changping, and Miyun districts of Beijing. The age and gender specific hospitalization rates and age-standardized hospitalization rates were calculated. Joinpoint regression model was used to explore the trend of the hospitalization rates, and the influencing factors of the hospital stay length and complications were analyzed.Results:The age-standardized hospitalization rate of the patients with herpes zoster was 10.82/100 000-18.43/100 000 in Beijing from 2017 to 2022 [annual percent change (APC) =5.86%, 95% CI: -2.80%-15.98%]. The age-standardized hospitalization rate of the cases with herpes zoster as the main diagnosis showed an upward trend (APC=11.35%, 95% CI: 7.21%-16.23%). The age-standardized hospitalization rate showed an upward trend in women (APC=14.34%, 95% CI: 7.95%-22.37%). The hospitalization rate showed a downward trend in age group 30-39 years (APC=-24.92%, 95% CI: -48.56% - -1.85%) and showed upward trends in age group 70-79 years and 80-109 years (APC=23.18%, 95% CI: 13.53%-35.58%; APC=4.90%, 95% CI: 1.18%-9.19%). Complications occurred in 66.28% (680/1 026) of the patients. The median hospital stay length was 9 (5,15) days, and the patients with high age (≥80 years) and two or more complications had longer hospital stay, which were 12 (6, 23) and 14 (7, 27) days respectively ( P<0.001). Conclusions:The hospitalization rate in women and the elderly aged ≥70 years with herpes zoster as the main diagnosis showed upward trends in Beijing in recent years. The elderly aged ≥80 years usually had longer hospital stay, showing a relatively disease burden level. More attention should be paid to development of intervention strategies, such as vaccine, for this population.

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Objective:To study the changes in serum small molecule metabolites after brucella infection in humans using untargeted metabolomics methods, and screening representative biomarkers. Methods:A total of 109 serum samples collected from January 2019 to December 2021 at the Brucellosis Clinic of the Baotou Center for Disease Control and Prevention were divided into acute phase group ( n = 40), chronic phase group ( n = 35) of brucellosis, and healthy group ( n = 34) based on clinical diagnosis. Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry technology was used to test serum samples and screen for differential metabolites. Receiver operating characteristic curve was used to evaluate the predictive ability of differential metabolites for brucellosis. Enriched pathways were screened using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to identify metabolic pathways significantly affected. Results:A total of 17 differential metabolites were screened between the acute phase group and the healthy group, and 12 differential metabolites were screened between the chronic phase group and the healthy group. There were a total of 5 differential metabolites (oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid) statistically significant among the three groups ( F = 16.84, 17.52, 14.31, 13.01, 20.76, P < 0.05). KEGG pathway analysis showed that the differential metabolites in the acute phase group were enriched in metabolic pathways such as ether lipid metabolism, glycerophosphate metabolism, sphingolipid signal and sphingolipid metabolism. The differential metabolites in the chronic phase group were enriched in metabolic pathways such as glycerophosphate metabolism, ether lipid metabolism, protein digestion and absorption metabolism. Conclusion:Untargeted metabolomics methods can screen out serum small molecule metabolites that undergo changes after brucella infection in the human body, including oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid can serve as potential biomarkers to distinguish brucellosis patients from healthy people.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.

Objective:To investigate the impact of air pollution on dynamic changes in lung function and further explore the association between genetic factors and lung function and its changes.Methods:Research data were from 14 506 participants in the United Kingdom Biobank with two complete baseline and follow-up lung function tests. Particulate matter [including particulate matter with aerodynamic diameter ≤2.5 μm and ≤10 μm (PM 2.5 and PM 10)], nitrogen dioxide (NO 2), and nitrogen oxides (NO x) concentrations were estimated using land-use regression models. Annual changes in lung function were calculated based on baseline and follow-up lung function tests. Polygenic risk scores (PRS) of lung function [forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), and the ratio of FEV 1 to FVC (FEV 1/FVC)] were constructed by genetic variations. The association between air pollution concentrations and lung function changes was analyzed by multiple linear regression models, and the impact of genetic factors on lung function and its changes was also assessed. Results:PM 2.5, PM 10, NO 2, and NO x showed a negative correlation with FVC changes [PM 2.5: -6.66 (95% CI: -9.92- -3.40) ml/year; PM 10: -0.40 (95% CI: -0.77- -0.03) ml/year; NO 2: -1.84 (95% CI: -2.60- -1.07) ml/year; NO x: -1.37 (95% CI: -2.27- -0.46) ml/year]. Additionally, PM 2.5, PM 10and NO 2 were also negatively correlated with changes in FEV 1 [PM 2.5: -3.19 (95% CI: -5.79- -0.59) ml/year; PM 10: -3.00 (95% CI: -5.92- -0.08) ml/year; NO 2: -0.95 (95% CI: -1.56- -0.34) ml/year]. PRS of lung function were positively correlated with baseline lung function (FVC, FEV 1, and FEV 1/FVC) and lung function changes (all β>0, all P<0.001). In different PRS stratification analyses, the effect of air pollution on lung function changes remained significant, and there was no apparent heterogeneity. Conclusions:PRS of lung function are significantly associated with baseline and lung function changes. Long-term exposure to air pollution accelerates the decline of lung function indicators such as FVC and FEV 1. The effects of air pollution are consistent in individuals with different genetic risk scores.

Objective To elucidate the regulatory effects of Glycerol Kinase(GLPK)on the inflammatory response induced by lipopolysaccharide(LPS)in mouse Raw264.7 macrophages.Methods Raw264.7 macrophages were cultured in vitro,and an inflammatory model was established through LPS induction.The transcriptional levels of inflammatory cytokines NF-κB,TNF-α,IL-6,and IL-1β were quantified using RT-qPCR.The expression and localization of GLPK were examined via Western blot and immunofluorescence.Additionally,Western blot analysis was employed to detect the levels of cellular pan-succinylation and H3K23su expression.ChIP-qPCR was utilized to assess the enrichment of H3K23su modification at the IL-10 promoter.The total reactive oxygen species production was measured using DCFH-DA probes,while mitochondrial ROS levels were determined with Mito-SOX probes.Mitochondrial membrane potential changes,indicative of mitochondrial dysfunction,were evaluated using JC-1 fluorescent probes.Furthermore,GLPK overexpression plasmids were transfected into cells to investigate the effects of GLPK on inflammatory responses,mitochondrial function,and epigenetic modifications.Results LPS treatment led to mitochondrial dysfunction,inflammatory responses exacerbation,succinylation modifications reduction,and GLPK protein expression decrease in Raw264.7 cells.Overexpression of GLPK in LPS-treated cells improved mitochondrial function and reduced the transcription of pro-inflammatory cytokines.ChIP-qPCR analysis revealed that GLPK overexpression could reverse the LPS-induced suppression of H3K23su modification at the IL-10 promoter,thereby attenuating the inflammatory response.Conclusion LPS mediates inflammatory responses in Raw264.7 macrophages through a GLPK-dependent H3K23 succinylation modification mechanism.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.
Animals ; Zebrafish ; Melatonin/pharmacology* ; Lipid Metabolism/drug effects* ; Disease Models, Animal ; Rotenone/pharmacology* ; Sleep Wake Disorders/metabolism* ; Parkinson Disease/metabolism* ; Motor Activity/drug effects* ; Sleep/drug effects*

Objective To elucidate the regulatory effects of Glycerol Kinase(GLPK)on the inflammatory response induced by lipopolysaccharide(LPS)in mouse Raw264.7 macrophages.Methods Raw264.7 macrophages were cultured in vitro,and an inflammatory model was established through LPS induction.The transcriptional levels of inflammatory cytokines NF-κB,TNF-α,IL-6,and IL-1β were quantified using RT-qPCR.The expression and localization of GLPK were examined via Western blot and immunofluorescence.Additionally,Western blot analysis was employed to detect the levels of cellular pan-succinylation and H3K23su expression.ChIP-qPCR was utilized to assess the enrichment of H3K23su modification at the IL-10 promoter.The total reactive oxygen species production was measured using DCFH-DA probes,while mitochondrial ROS levels were determined with Mito-SOX probes.Mitochondrial membrane potential changes,indicative of mitochondrial dysfunction,were evaluated using JC-1 fluorescent probes.Furthermore,GLPK overexpression plasmids were transfected into cells to investigate the effects of GLPK on inflammatory responses,mitochondrial function,and epigenetic modifications.Results LPS treatment led to mitochondrial dysfunction,inflammatory responses exacerbation,succinylation modifications reduction,and GLPK protein expression decrease in Raw264.7 cells.Overexpression of GLPK in LPS-treated cells improved mitochondrial function and reduced the transcription of pro-inflammatory cytokines.ChIP-qPCR analysis revealed that GLPK overexpression could reverse the LPS-induced suppression of H3K23su modification at the IL-10 promoter,thereby attenuating the inflammatory response.Conclusion LPS mediates inflammatory responses in Raw264.7 macrophages through a GLPK-dependent H3K23 succinylation modification mechanism.