Long-term exposure to fine particulate matter constituents in relation to chronic kidney disease: evidence from a large population-based study in China.

The effects of long-term exposure to fine particulate matter (PM2.5) constituents on chronic kidney disease (CKD) are not fully known. This study sought to examine the association between long-term exposure to major PM2.5 constituents and CKD and look for potential constituents contributing substantially to CKD. This study included 81,137 adults from the 2018 to 2019 baseline survey of China Multi-Ethnic Cohort. CKD was defined by the estimated glomerular filtration rate. Exposure concentration data of 7 major PM2.5 constituents were assessed by satellite remote sensing. Logistic regression models were used to estimate the effect of each PM2.5 constituent exposure on CKD. The weighted quantile sum regression was used to estimate the effect of mixed exposure to all constituents. PM2.5 constituents had positive correlations with CKD (per standard deviation increase), with ORs (95% CIs) of 1.20 (1.02-1.41) for black carbon, 1.27 (1.07-1.51) for ammonium, 1.29 (1.08-1.55) for nitrate, 1.20 (1.01-1.43) for organic matter, 1.25 (1.06-1.46) for sulfate, 1.30 (1.11-1.54) for soil particles, and 1.63 (1.39-1.91) for sea salt. Mixed exposure to all constituents was positively associated with CKD (1.68, 1.32-2.11). Sea salt was the constituent with the largest weight (0.36), which suggested its importance in the PM2.5-CKD association, followed by nitrate (0.32), organic matter (0.18), soil particles (0.10), ammonium (0.03), BC (0.01). Sulfate had the least weight (< 0.01). Long-term exposure to PM2.5 sea salt and nitrate may contribute more than other constituents in increasing CKD risk, providing new evidence and insights for PM2.5-CKD mechanism research and air pollution control strategy.

Potential therapeutic medicines for renal fibrosis: Small-molecule compounds and natural products.

Renal fibrosis is the pathological change process of chronic kidney disease deteriorating continuously. When the renal organ is stimulated by external stimuli, it will trigger the damage and phenotypic changes of some intrinsic cells in the kidney. When the body's autoimmune regulation or external treatment is not prompted enough to restore the organ, the pathological process is gradually aggravating, inducing a large amount of intracellular collagen deposition, which leads to the appearance of fibrosis and scarring. The renal parenchyma (including glomeruli and tubules) begins to harden, making it difficult to repair the kidney lesions. In the process of gradual changes in the kidney tissue, the kidney units are severely damaged and the kidney function shows a progressive decline, eventually resulting in the clinical manifestation of end-stage renal failure, namely uremia. This review provides a brief description of the diagnosis, pathogenesis, and potential therapeutic inhibitors of renal fibrosis. Since renal fibrosis has not yet had a clear therapeutic target and related drugs, some potential targets and relevant inhibitors are discussed, especially pharmacological effects and interactions with targets. Some existing natural products have potential efficacy for renal fibrosis, which is also roughly summarized, hoping that this article would have reference significance for the treatment of renal fibrosis.

Mediation of metabolic syndrome in the association between long-term exposure to particulate matter and incident cardiovascular disease: Evidence from a population-based cohort in Chengdu.

BACKGROUND: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. METHODS: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. RESULTS: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. CONCLUSIONS: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Targeting progranulin alleviated silica particles-induced pulmonary inflammation and fibrosis via decreasing Il-6 and Tgf-ß1/Smad.

Long term exposure to silica particles leads to various diseases, among which silicosis is of great concern. Silicosis is an interstitial lung disease caused by inhalation of silica particles in production environments. However, the mechanisms underlying silicosis remains unclear. Our previous studies revealed that progranulin (Pgrn) promoted the expression of pro-inflammatory factors in alveolar macrophages treated with silica particles and the secretion of extracellular matrix of pulmonary fibroblasts. Nevertheless, the role of Pgrn in silica particles-induced silicosis in vivo was unknown. This study found that silica particles increased Pgrn expression in silicosis patients. Pgrn deficiency reduced lung inflammation and fibrosis in silica particles-induced silicosis mouse models. Subsequently, based on transcriptional sequencing and interleukin (Il) -6 knockout mouse models, results demonstrated that Pgrn deficiency might decrease silicosis inflammation by reducing the production of Il-6, thereby modulating pulmonary fibrosis in the early stage of silicosis mouse models. Furthermore, another mechanism through which Pgrn deficiency reduced fibrosis in silicosis mouse models was the regulation of the transforming growth factor (Tgf) -ß1/Smad signaling pathway. Conclusively, Pgrn contributed to silicosis inflammation and fibrosis induced by silica particles, indicating that Pgrn could be a promising therapeutic target.

Role of metabolic risk factors in the relationship between ambient fine particulate matter and depressive symptoms: Evidence from a longitudinal population study.

BACKGROUND: There is growing evidence indicating a connection between fine particulate matter (PM2.5) and depressive symptoms. Metabolic risk factors are critical determinants of depressive symptoms. However, the mediating role of these factors on the association between PM2.5 and depressive symptoms remains elusive. We aimed to investigate whether and to what extent metabolic risk factors mediated the link between long-term PM2.5 exposure and depressive symptoms. METHODS: This study comprised 7794 individuals aged between 30 and 79 years who participated in two waves of the on-site surveys in the China Multi-Ethnic Cohort. Ambient PM2.5 concentrations were assessed utilizing a random forest method based on satellite data. We employed the Patient Health Questionnaire-9 to assess depressive symptoms at wave 2, and the overall as well as three sub-domain symptom scores (emotional, neurovegetative, and neurocognitive symptoms) were calculated. Three metabolic risk factors, including hypertension, diabetes, and dyslipidemia, were considered. Mediation analyses were conducted to assess the indirect effects of PM2.5 on depressive symptoms through metabolic risk factors. RESULTS: We found a positive association between chronic exposure to ambient PM2.5 and overall depressive symptoms as well as the three sub-domains. In mediation analyses, metabolic risk factors partially mediated the associations of PM2.5 on depressive symptoms. The natural indirect effects (RR, 95% CI) of PM2.5 on overall, emotional, neurovegetative, and neurocognitive symptoms mediated through metabolic risk factors were 1.004(1.001, 1.007), 1.004 (1.001, 1.008), 1.004 (1.001, 1.007), and 1.003(0.999, 1.007), respectively. Larger indirect effects were found in elderly participants (mediated proportion, 29.3%), females (13.3%), and people who did not consume alcohol (19.6%). CONCLUSIONS: Metabolic risk factors may act as mediators in the relationship between chronic PM2.5 exposure and depression. Treatment of metabolic risk factors may be an opportunity to reduce the burden of depression caused by long-term exposure to PM2.5.

Development of a 3 MV coaxial peaking capacitor for large-scale electromagnetic pulse simulator.

Coaxial peaking capacitor is a key component in high-altitude electromagnetic pulse (EMP) simulators with fast front pulse output. It poses significant technical and engineering challenges in limiting radiation field amplitude and test space. This paper presents the design and testing of a 180 pF, 3 MV coaxial peaking capacitor with improved insulation performance. In the insulation design, the length of the dielectric film is extended to reduce the background electric field on the flashover path. The electric field threshold obtained from image diagnosis is used as a reference. During capacitor testing, the insulation characteristics are diagnosed using both direct and indirect methods. The voltage measured by a D-dot probe, the output waveform of the Marx generator in the primary source, and the radiation field waveform are analyzed to understand the flashover characteristics of the capacitor and to improve the reliability of the test results. The experimental results demonstrate that the peaking capacitor can operate stably at 3.0 MV. If flashover occurring on the dropping edge of the pulse is permitted, the operating voltage can be greater than 3.7 MV without significantly affecting the radiation field waveform. The analysis on the surface flashover morphology of the peaking capacitor reveals that the flashover mainly occurs at the dropping edge of the capacitor's waveform, indicating that the damage to the film is not serious. This research significantly increases the working voltage of coaxial peaking capacitors and contributes to the development of high-altitude EMP simulation technology.

Regional and epidemiological characteristics of tuberculosis and treatment outcomes in West China.

Objective: To understand the prevalence and treatment outcome of tuberculosis in a typically regional County from 2016 to 2021, so as to provide reference and basis for the prevention and treatment of tuberculosis in this area. Methods: Descriptive epidemiological methods were used to analyze the population, time and location distribution of pulmonary tuberculosis in Dazhu County from 2016 to 2021. The incidence rates were compared by Chi-square test and trend test, time distribution combined with seasonal index analysis, and the test level was α = 0.05. Results: A total of 2,899 cases of pulmonary tuberculosis were reported in Dazhu County from 2016 to 2021, with an average annual incidence rate of 44.29/100,000 and standardized reported incidence rate was 36.77/100,000, showing a downward trend year by year (χ2 trend = 124.629, p < 0.001). A total of 955 cases of pathogen positive were reported, showing an increasing trend year by year (χ2 trend = 59.773, p < 0.001). In terms of time distribution, the incidence rate was high in autumn and winter, and September and December were the peak of the disease in the whole year, and the overall trend increased first, then decreased and once again increased (F = 5.861, p < 0.05). In regional distribution, the highest annual average reported incidence rate was in concentrated population. The incidence rate of male was higher than female in population distribution. After standardization, the overall incidence rate increased from 34 to 45 years old (χ2 trend = 6963.101, p < 0.001), and decreased after 45 years old (χ2 trend = 1104.393, p < 0.001). The occupation distribution is mainly farmers (82.75%). The overall arrival rate and cure rate of patients showed an upward trend year by year (χ2 trend = 4.306, χ2 trend = 5.772, p < 0.001). Conclusion: The incidence rate of pulmonary tuberculosis in this regional county is decreasing year by year. Male patients are higher than female patients and have certain seasonal characteristics. Attention should be paid to male, older adult, farmers and other groups, and corresponding measures should be taken to strengthen the prevention and treatment of tuberculosis in high incidence areas.

Metabolomic profiling of Wilson disease, an inherited disorder of copper metabolism, and diseases with similar symptoms but normal copper metabolism.

BACKGROUND: Wilson's disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson's disease patients (who exhibit similar symptoms but have normal copper levels). RESULTS: Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson's disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson's disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson's disease). CONCLUSIONS: Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.

Anemia is associated with long-term exposure to PM2.5 and its components: a large population-based study in Southwest China.

Background: Anemia is linked to PM2.5 (particulate matter with aerodynamic diameters of ⩽2.5 µm) exposure, which can increase the risk of various negative health outcomes. It remains unclear which PM2.5 components are associated with anemia and the respective contribution of each component to this association. Objective: This study aimed at investigating the association between PM2.5 and anemia in the general population and to identify the most critical PM2.5 toxic components in this association. Design: Cross-sectional study. Methods: Our study involved a large cohort of 73,511 individuals aged 30-79 from China's multi-ethnic population. We employed satellite observations and the chemical transport model (GEOS-Chem)to estimate the long-term exposure to PM2.5 and its components. Anemia was defined, according to WHO guidelines, as Hb levels below 130 g/L for men and below 120 g/L for women. Through logistic regression, we investigated the association between PM2.5 components and anemia. By utilizing weighted quantile sum (WQS) analysis, we identified key components and gained insights into their combined impact on anemia. Overall, our study sheds light on the relationship between PM2.5 exposure, its constituents, and the risk of anemia in a large cohort. Results: PM2.5 and three components, nitrate (NIT), organic matter (OM), and soil particles (SOIL), were associated with anemia. Per-standard deviation increase in the 3-year average concentrations of PM2.5 [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.01, 1.28], NIT (1.20, 1.06, 1.35), OM (1.17, 1.04, 1.32), and SOIL (1.22, 1.11, 1.33) were associated with higher odds of anemia. In WQS regression analysis, the WQS index was associated with anemia (OR: 1.29, 95% CI: 1.13, 1.47). SOIL has the highest weight among all PM2.5 components. Conclusions: Long-term exposure to PM2.5 and its constituents is associated with anemia. Moreover, SOIL might be the most critical component of the relationship between PM2.5 and anemia. Our research increases the evidence of the association between PM2.5 and anemia in the general population, and targeted emission control measures should be taken into consideration to mitigate the adverse effects of PM2.5-related anemia.

Long-term exposure to ambient PM2.5 constituents is associated with dyslipidemia in Chinese adults.

BACKGROUND: Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) consists of various toxic constituents. However, the health effect of PM2.5 may differ depending on its constituents, but the joint effect of PM2.5 constituents remains incompletely understood. OBJECTIVE: Our goal was to evaluate the joint effect of long-term PM2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent. METHODS: This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C) < 1.04 mmol/L, and low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol/L. The logistic regression model was utilized to examine the single effect of PM2.5 constituents on dyslipidemia, while the weighted quantile sum regression model for the joint effect. RESULTS: The odds ratio with a 95 % confidence interval for dyslipidemia positively related to per-SD increase in the three-year average was 1.29 (1.20-1.38) for PM2.5 mass, 1.25 (1.17-1.34) for black carbon, 1.24 (1.16-1.33) for ammonium, 1.33 (1.24-1.43) for nitrate, 1.34 (1.25-1.44) for organic matter, 1.15 (1.08-1.23) for sulfate, 1.30 (1.22-1.38) for soil particles, and 1.12 (1.05-1.92) for sea salt. Stronger associations were observed in individuals < 65 years of age, males, and those with low physical activity. Joint exposure to PM2.5 constituents was positively related to dyslipidemia (OR: 1.09, 95 %CI: 1.05-1.14). Nitrate was identified as the constituent with the largest weight (weighted at 0.387). CONCLUSIONS: Long-term exposure to PM2.5 constituents poses a significant risk to dyslipidemia and nitrate might be the most responsible for the risk. These findings indicate that reducing PM2.5 constituent exposures, especially nitrate, could be beneficial to alleviate the burden of disease attributed to PM2.5-related dyslipidemia.

Application of mNGS in the study of pulmonary microbiome in pneumoconiosis complicated with pulmonary infection patients and exploration of potential biomarkers.

Background: Pneumoconiosis patients have a high prevalence of pulmonary infections, which can complicate diagnosis and treatment. And there is no comprehensive study of the microbiome of patients with pneumoconiosis. The application of metagenomic next-generation sequencing (mNGS) fills the gap to some extent by analyzing the lung microbiota of pneumoconiosis population while achieving accurate diagnosis. Methods: We retrospectively analyzed 44 patients with suspected pneumoconiosis complicated with pulmonary infection between Jan 2020 and Nov 2022. Bronchoalveolar lavage fluid (BALF) specimens from 44 patients were collected and tested using the mNGS technology. Results: Among the lung microbiome of pneumoconiosis patients with complicated pulmonary infection (P group), the most frequently detected bacteria and fungi at the genus level were Streptococcus and Aspergillus, at the species level were Streptococcus pneumoniae and Aspergillus flavus, respectively, and the most frequently detected DNA virus was Human gammaherpesvirus 4. There was no significant difference in α diversity between the P group and the non-pneumoconiosis patients complicated with pulmonary infection group (Non-P group) in pulmonary flora, while P< 0.01 for ß diversity analysis, and the differential species between the two groups were Mycobacterium colombiense and Fusobacterium nucleatum. In addition, we monitored a high distribution of Malassezia and Pneumocystis in the P group, while herpes virus was detected in the majority of samples. Conclusions: Overall, we not only revealed a comprehensive lung microbiome profile of pneumoconiosis patients, but also compared the differences between their microbiome and that of non-pneumoconiosis complicated with pulmonary infection patients. This provides a good basis for a better understanding of the relationship between pneumoconiosis and microorganisms, and for the search of potential biomarkers.

Ambient PM2.5 and its components associated with 10-year atherosclerotic cardiovascular disease risk in Chinese adults.

BACKGROUND: Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. METHODS: Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35-74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. RESULTS: Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12-1.35), black carbon (1.21, 1.11-1.33), ammonium (1.21, 1.10-1.32), nitrate (1.25, 1.14-1.38), organic matter (1.29, 1.18-1.42), sulfate (1.17, 1.07-1.28), and soil particles (1.15, 1.04-1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11-1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. CONCLUSION: Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.

Microbiota and mycobiota in bronchoalveolar lavage fluid of silicosis patients.

BACKGROUND: The contribution of bronchoalveolar lavage fluid (BALF) microbiota and mycobiota to silicosis has recently been noticed. However, many confounding factors can influence the accuracy of BALF microbiota and mycobiota studies, resulting in inconsistencies in the published results. In this cross-sectional study, we systematically investigated the effects of "sampling in different rounds of BALF" on its microbiota and mycobiota. We further explored the relationship between silicosis fatigue and the microbiota and mycobiota. METHODS: After obtaining approval from the ethics board, we collected 100 BALF samples from 10 patients with silicosis. Demographic data, clinical information, and blood test results were also collected from each patient. The characteristics of the microbiota and mycobiota were defined using next-generation sequencing. However, no non-silicosis referent group was examined, which was a major limitation of this study. RESULTS: Our analysis indicated that subsampling from different rounds of BALF did not affect the alpha- and beta-diversities of microbial and fungal communities when the centrifuged BALF sediment was sufficient for DNA extraction. In contrast, fatigue status significantly influenced the beta-diversity of microbes and fungi (Principal Coordinates Analysis, P = 0.001; P = 0.002). The abundance of Vibrio alone could distinguish silicosis patients with fatigue from those without fatigue (area under the curve = 0.938, 95% confidence interval [CI] 0.870-1.000). Significant correlations were found between Vibrio and haemoglobin levels (P < 0.001, ρ = -0.64). CONCLUSIONS: Sampling in different rounds of BALF showed minimal effect on BALF microbial and fungal diversities; the first round of BALF collection was recommended for microbial and fungal analyses for convenience. In addition, Vibrio may be a potential biomarker for silicosis fatigue screening.

Role of gender and age in features of Wilson's disease.

Background: Wilson's disease (WD) is a recessive genetic disorder characterized by copper metabolism dysfunction. It is difficult to obtain an accurate diagnosis due to its variable clinical presentation. This study aimed to describe the clinical characteristics and diagnostic particularities in a series of Chinese WD patients. Methods: The medical records of 371 patients with WD retrieved from January 2005 to December 2020 were retrospectively reviewed. Results: The incidence of WD has a male predominance in the adult population. However, the difference in sex distribution is not significant in the pediatric population. Females have an earlier symptom onset than males. The most common initial symptoms were neuropsychiatric manifestations both in the pediatric population (49.7%) and adult population (69.8%), and there was a male predominance (61.8%). Eighty-two percent of patients presented with more than two neurologic symptoms. Fifty-two (14%) patients presented with psychiatric symptoms. The most common WD phenotype was the neuropsychiatric form (48%). The age of onset occurred earlier in patients with the hepatic phenotype than in those with the neuropsychiatric phenotype. Moreover, there was a significant difference in sex distribution regarding phenotype. Females presented with a hepatic phenotype more often than males, and the neuropsychiatric phenotype occurred more frequently in males with an older onset age. Further study showed that the age at onset was a deciding factor for predicting the neuropsychiatric phenotype among the hepatic phenotype. However, sex did not correlate with the phenotype. Conclusion: Males seem to have a higher disease susceptibility, with symptom onset later than females. Males frequently present with a neuropsychiatric phenotype, while females present with a hepatic phenotype. Age at onset was a deciding factor for predicting the WD phenotype. Further studies focusing on the effect of estrogens on the pathology of WD are suggested.

Not all Rectal Cancer Patients Could Benefit From the Surgery on the Primary Site.

AIM: Previous studies have provided evidence that primary site surgery can improve the prognosis of rectal cancer patients, even in those with advanced age and distant metastasis, though results have been inconsistent. The current study aims to determine if all rectal cancer patients are likely to benefit from surgery in terms of overall survival. METHODS: This study examined the impact of primary site surgery on the prognosis of rectal cancer patients diagnosed between 2010 and 2019 using multivariable Cox regression analysis. The study also stratified patients by age group, M stage, chemotherapy, radiotherapy, and number of distant metastatic organs. The propensity score matching method was used to balance observed covariates between patients who received and did not receive surgery. The Kaplan-Meier method was used to analyze the data, and the log-rank test was used to determine differences between patients who did and did not undergo surgery. RESULTS: The study included 76,941 rectal cancer patients, with a median survival of 81.0 months (95% CI: 79.2-82.8 months). Of these patients, 52,360 (68.1%) received primary site surgery, and they tended to be younger, have higher differentiated grade, earlier T, N, M stage, and lower rates of bone, brain, lung, and liver metastasis, chemotherapy, and radiotherapy than those without surgery. Multivariable Cox regression analysis revealed that surgery had a protective effect on the prognosis of rectal cancer patients, including those with advanced age, distant metastasis, and multiple organ metastasis, but not in patients with four organ metastases. The results were also confirmed using propensity score matching. CONCLUSION: Not all rectal cancer patients could benefit from the surgery on the primary site, especially the patients with more than four distant metastases. The results could help the clinicians to tailor targeted treatment regimens and provide a guideline for making surgical decisions.

Advances in CD73 inhibitors for immunotherapy: Antibodies, synthetic small molecule compounds, and natural compounds.

Tumors, a disease with a high mortality rate worldwide, have become a serious threat to human health. Exonucleotide-5'-nucleotidase (CD73) is an emerging target for tumor therapy. Its inhibition can significantly reduce adenosine levels in the tumor microenvironment. It has a better therapeutic effect on adenosine-induced immunosuppression. In the immune response, extracellular ATP exerts immune efficacy by activating T cells. However, dead tumor cells release excess ATP, overexpress CD39 and CD73 on the cell membrane and catabolize this ATP to adenosine. This leads to further immunosuppression. There are a number of inhibitors of CD73 currently under investigation. These include antibodies, synthetic small molecule inhibitors and a number of natural compounds with prominent roles in the anti-tumor field. However, only a small proportion of the CD73 inhibitors studied to date have successfully reached the clinical stage. Therefore, effective and safe inhibition of CD73 in oncology therapy still holds great therapeutic potential. This review summarizes the currently reported CD73 inhibitors, describes their inhibitory effects and pharmacological mechanisms, and provides a brief review of them. It aims to provide more information for further research and development of CD73 inhibitors.

Exploratory study on noninvasive biomarker of silicosis in exhaled breath by solid-phase microextraction-gas chromatography-mass spectrometry analysis.

BACKGROUND: As a chronic occupational disease, silicosis could cause irreversible and incurable impair to the lung. The current diagnosis of silicosis relies on imaging of X-ray or CT, but these methods cannot detect lung lesions in the early stage of silicosis. OBJECTIVE: To establish a regular screening and early diagnosis methods for silicosis, which could be helpful for the prevention and treatment of silicosis. METHODS: A total of 161 subjects were enrolled in the study, including 69 patients with silicosis (SILs) and 92 healthy controls. The exhaled breath samples of the subjects were collected with breath sampler and Tedlar bag. The analysis of volatile organic compounds (VOCs) in exhaled breath was performed by solid-phase microextraction (SPME) combined with gas chromatography mass spectrometry (GC-MS). RESULTS: After excluding the pollutants from sampling bags and instruments, 86 VOCs have been identified in the exhaled breath. The orthogonal partial least squares-discriminant analysis (OPLS-DA) was employed for the screening of potential biomarkers of silicosis. Those components that related to smoking were also excluded from the biomarkers. Finally, nine possible biomarkers for silicosis were screened out, including 2,3-butanedione, ethyl acetate, chlorobenzene, o-cymene, 4-ethylhex-2-ynal, 3,5-dimethyl-3-heptanol, hydroquinone, phthalic anhydride and 5-(2-methylpropyl)nonane. Based on these biomarkers screened, a predicted model for silicosis was generated with the accuracy of 89.61%. CONCLUSION: The nine biomarkers in exhaled breath were preliminarily screened out for the early diagnosis of silicosis, which can be helpful to the establishment of a noninvasive screening method for silicosis. Follow-up studies should be conducted to further verify these markers.

Prenatal and early-life exposure to traffic-related air pollution and allergic rhinitis in children: A systematic literature review.

BACKGROUND: Traffic-related air pollution (TRAP) is hypothesised to play a role in the development of allergic rhinitis (AR). Prenatal and early-life exposure to traffic-related air pollution is considered critical for later respiratory health. However, we could not find any articles systematically reviewing the risk of prenatal and early-life exposure to traffic-related air pollution for allergic rhinitis in children. METHODS: A systematic literature search of PubMed, Web of Science and Medline was conducted to identify studies focused on the association between prenatal and early-life exposure to TRAP and AR in children. Other inclusion criteria were: 1) original articles; 2) based upon prospective or retrospective studies or case-control studies; and 3) publications were restricted to English. Literature quality assessment was processed using the Newcastle-Ottawa Scale (NOS) evaluation scale. This systematic literature review has been registered on the prospero (crd.york.ac.uk/prospero) with the following registry number: CRD42022361179. RESULTS: Only eight studies met the inclusion criteria. The exposure assessment indicators included PM2.5, PM2.5 absorbance, PM10, NOx, CO, and black carbon. On the whole, exposure to TRAP during pregnancy and the first year of life were positively associated with the development of AR in children. CONCLUSIONS: This systematic review presents supportive evidence about prenatal and early-life exposure to TRAP and the risk of AR in children.

The Role of Hyperbaric Oxygen Therapy in the Treatment of Surgical Site Infections: A Narrative Review.

Surgical site infections (SSIs) are among the most prevalent postoperative complications, with significant morbidity and mortality worldwide. In the past half century, hyperbaric oxygen therapy (HBOT), the administration of 100% oxygen intermittently under a certain pressure, has been used as either a primary or alternative therapy for the management or treatment of chronic wounds and infections. This narrative review aims to gather information and evidence supporting the role of HBOT in the treatment of SSIs. We followed the Scale for the Quality Assessment of Narrative Review Articles (SANRA) guidelines and scrutinized the most relevant studies identified in Medline (via PubMed), Scopus, and Web of Science. Our review indicated that HBOT can result in rapid healing and epithelialization of various wounds and has potential beneficial effects in the treatment of SSIs or other similar infections following cardiac, neuromuscular scoliosis, coronary artery bypass, and urogenital surgeries. Moreover, it was a safe therapeutic procedure in most cases. The mechanisms related to the antimicrobial activity of HBOT include direct bactericidal effects through the formation of reactive oxygen species (ROS), the immunomodulatory effect of HBOT that increase the antimicrobial effects of the immune system, and the synergistic effects of HBOT with antibiotics. We emphasized the essential need for further studies, especially randomized clinical trials and longitudinal studies, to better standardize HBOT procedures as well as to determine its full benefits and possible side effects.

Evaluation of environmental factors and microbial community structure in an important drinking-water reservoir across seasons.

The composition of microbial communities varies in water and sediments, and changes in environmental factors have major effects on microbiomes. Here, we characterized variations in microbial communities and physicochemical factors at two sites in a large subtropical drinking water reservoir in southern China. The microbiomes of all sites, including the diversity and abundance of microbial species, were determined via metagenomics, and the relationships between microbiomes and physicochemical factors were determined via redundancy analysis. The dominant species in sediment and water samples differed; Dinobryon sp. LO226KS and Dinobryon divergens were dominant in sediment samples, whereas Candidatus Fonsibacter ubiquis and Microcystis elabens were dominant in water. The diversity was also significantly different in microbial alpha diversity between water and sediment habitats (p < 0.01). The trophic level index (TLI) was the major factor affecting the microbial community in water samples; Mycolicibacterium litorale and Mycolicibacterium phlei were significantly positively related to TLI. Furthermore, we also studied the distribution of algal toxin-encoding genes and antibiotic-resistant genes (ARGs) in the reservoir. It found that water samples contained more phycotoxin genes, with the cylindrospermopsin gene cluster most abundant. We found three genera highly related to cylindrospermopsin and explored a new cyanobacteria Aphanocapsa montana that may produce cylindrospermopsin based on the correlation through network analysis. The multidrug resistance gene was the most abundant ARG, while the relationship between ARGs and bacteria in sediment samples was more complicated than in water. The results of this study enhance our understanding of the effects of environmental factors on microbiomes. In conclusion, research on the properties, including profiles of algal toxin-encoding genes and ARGs, and microbial communities can aid water quality monitoring and conservation.