Objective To study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To establish the UPLC fingerprint evaluation system of Viticis Fructus; To comprehensively evaluate the quality of Viticis Fructus and its processed products combining with multivariate statistical methods and compositional variance analysis.Methods:19 batches of Viticis Fructus from different regions were collected and processed by frying process into decoction pieces. The separation was operated on Waters CORTECS T3 C18 chromatographic column (100 mm × 2.1 mm, 1.6 μm). Acetonitrile and 0.1% phosphoric acid water were used as mobile phases for gradient elution, to establish the UPLC fingerprints of Viticis Fructus. The UPLC fingerprints of Viticis Fructus were analyzed using similarity evaluation, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA). The contents of seven active components in the samples of Viticis Fructus and fried Viticis Fructus were determined.Results:A total of 26 common peaks were identified in the fingerprints of 38 batches of samples, and 7 components were identified. Similarity evaluation results demonstrated that the chemical components of Viticis Fructus from Jingdezhen City, Jiangxi Province, were significantly different from those of other regions. The results of PCA and PLS-DA analysis showed that the chemical components of Viticis Fructus and fried Viticis Fructus could be clearly distinguished, and the processing process had an impact on the components. The results of content determination showed that the contents of some components increased or decreased after frying. The analysis results of grey correlation method and TOPSIS method show that the medicinal materials in Jiujiang City, Jiangxi Province have a high score ranking and stable quality.Conclusion:This study successfully establishes the fingerprints of Viticis Fructus and its processed products, grey correlation method and TOPSIS method analysis revealed the quality differences of samples from different origins, which providing a scientific basis for the quality control and evaluation of Viticis Fructus and its processed products.

Objective To observe the clinical efficacy of Fuyuan Capsules combined with Xingnao Kaiqiao acupuncture in the treatment of vascular dementia(VD),and to explore its possible mechanism of action.Methods A total of 204 cases of patients with a definitive diagnosis of VD admitted to the wards and outpatient clinics of Hengshui Hospital of Traditional Chinese Medicine from October 2019 to October 2022 were selected for the study.The patients were randomly divided into observation group and control group according to the random number table method,with 102 cases in each group.The patients in both groups were treated with symptomatic treatments such as blood pressure-controlling,glucose-lowering,blood lipids-regulating,along with cognitive function training.The control group was treated with Xingnao Kaiqiao acupuncture,and the observation group was given oral administration of Fuxing Capsules on the basis of the treatment in the control group.One week constituted a course of treatmen,and eight consecutive courses of treatment were carried out.After two months of treatment,the clinical efficacy of the two groups was evaluated.The changes in the scores of the Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA),Revised Hasegama's Dementia Scale(HDS-R),and Clinical Dementia Rating Scale(CDR)were observed in the patients of the two groups before and after treatment.The changes in the scores of the Activity of Daily Living Scale(ADL),Hachinski Ischemic Scale(HIS),and the traditional Chinese medicine(TCM)syndrome scores before and after treatment were compared in patients of the two groups.The changes in the expression level of neuregulin 1(NRG1)before and after treatment in patients of the two groups were detected.Results(1)During the study,two cases fell off from both groups,respectively.Finally,100 cases in the observation group and 100 cases in the control group were included in the efficacy statistics.(2)After treatment,the MMSE and MoCA scores of the patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the HDS-R and CDR scores of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(4)After treatment,the ADL and HIS scores of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(5)After treatment,the TCM syndrome scores of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(6)The total effective rate was 84.00％(84/100)in the observation group and 67.00％(67/100)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P＜0.05).(7)After treatment,the NRG1 levels of patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).Conclusion Fuyuan Capsules combined with Xingnao Kaiqiao acupuncture in the treatment of VD can significantly improve the clinical symptoms of patients,enhance the cognitive function,and effectively increase the serum NRG 1 level,so as to improve their quality of life.

Objective To investigate the feasibility of using the cell-free DNA(cfDNA)carrying tissue-specific mutations as biomarkers for assessing the severity of exercise-induced tissue injury.Methods Based on a public gene expression database,ten tissue-specific and highly-expressed genes were selected for each of ten different human tissues.A total of 34 young healthy volunteers were recruited,and their peripheral blood samples were collected after running 5 km per day for one week.Genomic DNA from leukocytes,plasma exosomal RNA,and plasma cfDNA were extracted and subjected to high-throughput sequencing respectively.Tissue-specific somatic mutations in plasma exosomal RNA were identified,and the relationship between cfDNA carrying these mutations and traditional protein biomarkers was analyzed.Results Tissue-specific cfDNA mutations related to five tissues(myocardium,skeletal muscle,intestine,stomach,and kidney)were detected in more than five volunteers.The correlation coefficients between total plasma cfDNA levels and the levels of tissue-specific protein biomarkers associated with these five tissues were less than 0.3(n=34,r=-0.51-0.28,P=0.0022-0.65).Notably,for each specific tissue,the levels of tissue-specific cfDNA mutations were positively correlated with the corresponding protein biomarker levels,and correlation coefficients were over 0.8(n=7-13,r=0.81-0.92,P=9.0×10-4-0.020).Conclusion Tissue-specific cfDNA mutations may serve as novel potential biomarkers for non-invasive evaluation of exercise-related tissue injury.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Background::Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.Methods::A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.Results::The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% ( P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis ( P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). Conclusion::Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.