The joint toxicity effect of glyphosate and cadmium in a concentration-dependent manner on nematode Caenorhabditis elegans.

The co-occurrence of glyphosate (GPS), a commonly used organophosphorus herbicide, and cadmium (Cd), a neurotoxic metal, in agricultural environments prompts concerns about their combined toxic effects on ecosystems. This study explores the combined effects of GPS and Cd on the model organism Caenorhabditis elegans (C. elegans), to understand their cumulative effects in organismal living environments. We investigated the interaction between GPS and Cd over 24 hours using a comprehensive approach that included a variety of toxicity endpoints as well as the novel Automated Recognition and Statistics Tool (NCLE) for body bend measurement. Our data show a concentration-dependent interplay in which antagonistic effects at lower concentrations reduce phenotypic damage while synergistic effects emerge at higher concentrations, particularly at GPS's LC50. Transcriptome analysis under antagonistic conditions revealed significant downregulation of Cd toxicity-related genes and identified Y22D7AL.16, which has a C2H2-type zinc finger domain, as a novel gene involved in metal stress response, implying an alternative Cd-resilience mechanism. The expression profile of this gene shows that it plays a larger role in both development and metal stress adaption. These findings highlight the complexities of compound pollutant interactions, emphasizing the importance of including such dynamics in environmental risk assessments and control techniques.

Analysis of the Improvement Sequence in Insomnia Symptoms and Factors Influencing the Treatment Outcomes of Smartphone-Delivered CBT in Patients with Insomnia Disorder.

Background: The effectiveness of medication combined with smartphone-delivered cognitive behavioral therapy for insomnia (CBT-I) has been well verified, but there are few studies on the sequence of remission of insomnia symptoms. This study aims to understand the sequence of symptom improvement and the factors influencing the treatment effectiveness in patients with insomnia. Methods: Smartphone-delivered CBT, as a form of Online CBT, allows for training through mobile devices at any time and place. We utilized the Good Sleep 365 app to conduct a survey, involving 2820 patients who met the baseline inclusion criteria. These patients were assessed using a general demographic questionnaire and the Pittsburgh Sleep Quality Index (PSQI) to evaluate general demographic information and insomnia symptoms, and subsequently underwent CBT training using the Good Sleep 365 app. A total of 1179 patients completed follow-ups at 4 weeks, 8 weeks, 16 weeks, and 24 weeks. Results: At 4 weeks and 8 weeks, the descending order of the reduction rates of PSQI components (excluding component 6: use of sleeping medication) was: sleep latency, subjective sleep quality, sleep efficiency, sleep disturbance, sleep maintenance, and daytime dysfunction. At 16 weeks and 24 weeks, the descending order was subjective sleep quality, sleep latency, sleep efficiency, daytime dysfunction, sleep maintenance, and sleep disturbance. There were significant differences in the reduction rates of PSQI components (excluding component 6: use of sleeping medication) both at the same follow-up times and at different follow-up times (all P<0.05). Multivariable logistic regression analysis showed that patients older than 30 years and those with a college degree or above had better treatment outcomes, whereas those with a disease duration of more than three years had worse outcomes. Conclusion: The sequence of symptom improvement in patients with insomnia changes over time, and age, educational level, and duration of disease are factors influencing treatment outcomes.

Unraveling the synergistic promotion mechanism of Fe0 coupling phragmites australis biomass for nitrogen removal in coastal wetland: From low to moderate salinities.

The simulated coastal constructed wetlands supplemented with Fe0 and phragmites australis (P.A) biomass (CW-M) were constructed to improve nitrogen removal under different salinities (0-15‰). Results showed that the denitrification performance of CW-M were improved significantly, with the higher NO3--N removal of 72-94% and lower N2O emission flux, when compared with mono-P.A biomass(CW-bio), mono-Fe0 system (CW-Fe) and control system. The nitrogen removal showed a trend of first increasing (0‰-7‰) and then decreasing (7‰-15‰) with the highest NO3--N removal of 94% and enhanced removal efficiency of 41% in CW-M. Fe0 and P.A biomass coupling could reduce the stress of salinity on denitrification. Batch experiments have demonstrated that Fe0 and P.A biomass could mutually stimulate more total organic carbon and total iron (TFe) release as electron donors for denitrification. Meanwhile, appropriate salinity could also promote the release of TFe. The typical heterotrophic denitrifying genera Bacillus and iron autotrophic denitrifying genera Thermomonas have the highest proportion in CW-M, with 21.83% and 0.10%, respectively. Fe0 and P.A biomass adding simultaneously promoted the carbon and iron metabolism, further enhancing the nitrogen metabolism process. The joint enhancement of autotrophic and heterotrophic denitrification contributes to NO3--N removal in CW-M for treating saline, low C/N wastewater in coastal wetlands.

Construction of sensitive quality indicators for rapid rehabilitation care of patients after combined pancreaticoduodenectomy.

AIM: To construct evidence-based sensitive quality indicators for patients' rapid rehabilitation care after combined pancreaticoduodenectomy (PD) and to provide a reference for clinical nursing professionals to scientifically evaluate the quality of patients' rehabilitation post-PD. BACKGROUND: Since PD is associated with higher surgical risk and anastomotic complications, it leads to higher complication rates and longer postoperative recovery cycles. This reiterates the need for rapid recovery of patients after PD; however, the evaluation of sensitive nursing care indicators regarding rapid recovery post-PD has not yet been established to date. METHODS: Based on the Donabedian structure-process-result theory model, we used available literature, semi-structured interviews, the Delphi method, and hierarchical analysis to establish a sensitive indicator system for patients' rapid rehabilitation after PD and evaluate the importance of such indicators. RESULTS: There were two rounds of expert correspondence, and the effective recovery rate of the questionnaires of these rounds was 100%. The expert authority coefficients, as well as the Kendall coordination coefficients of the expert opinions, were 0.859 and 0.872 as well as 0.423 and 0.431, with statistically significant differences (p < 0.05), respectively. Consequently, we developed a sensitive quality index system for patients' rapid rehabilitation care after combined PD, including 3 first-level, 12 s-level, and 23 third-level indexes, respectively. CONCLUSION: The constructed sensitive quality index system developed for patients' rapid rehabilitation nursing care after combined PD is standardized, practical, and aligned with the specialty characteristics. Furthermore, this might help greatly in improving the quality and safety of patients' rapid rehabilitation nursing care after combined PD, standardizing nursing management skills, and enhancing nursing quality.

Toralactone alleviates cisplatin-induced acute kidney injury by modulating the gut microbiota-renal axis.

BACKGROUND: Gut microbiota has been reported to be perturbed by cisplatin and to modulate the nephrotoxicity of chemotherapeutic agents. However, the critical role of toralactone, a bioactive components of Cassia obtusifolia L. seeds, in modulating the gut microbiota in the pathogenesis of cisplatin-induced nephrotoxicity remains to be elucidated. METHODS: In this study, we verified the reno-protective effects of toralactone and compared the composition and function of the gut microbiota in the normal, cisplatin-treated and low or high dose of toralactone-treated mice using 16S rDNA gene sequencing. We also investigated the gut microbiota related LPS/TLR4/NF-κB/TNF-α pathway in renal tissue. To elucidate the causal relationship between gut dysbiosis and cisplatin nephrotoxicity, an antibiotic cocktail was administered to deplete the gut microbiota and fecal microbiota transplantation (FMT) was performed prior to cisplatin treatment. RESULTS: The renal histopathology showed that toralactone significantly alleviated cisplatin-induced renal injury. 16S rDNA gene sequencing analysis demonstrated that toralactone treatment effectively reversed cisplatin-induced gut microbiota dysbiosis in mice. FMT from toralactone-treated mice to cisplatin-induced kidney injury mice was observed to have the reno-protective effects, and deletion of gut microbiota by antibiotics was found to negate the reno-protective effect of toralactone. Interestingly, the renal tissue of cisplatin-associated kidney injury mice showed activation of the LPS/TLR4/NF-κB pathway and increase in TNF-α within the renal tissue, whereas toralactone treatment was observed to inhibit the LPS/TLR4/NF-κB/TNF-α pathway. CONCLUSION: This study elucidated the reno-protective effects for the first time, demonstrating that it exerts its beneficial effects through the gut microbiota, which mediate the LPS/TLR4/NF-κB/TNF-α inflammatory pathway. It may help to develop therapeutic approaches using toralactone and targeted restoration of the gut microbiota.

Unveiling the microplastic perturbation on surface flow constructed wetlands with macrophytes of different life forms: Responses of nitrogen removal and sensory quality.

Microplastics (MPs) discharging into constructed wetlands pose risks to these ecosystems. Nevertheless, the perturbation of MPs to different types of macrophytes, which play important roles in purifying pollutants of wetlands, has not been fully elucidated. In this study, polystyrene MPs (PS-MPs) perturbation on nitrogen removal and sensory quality of surface flow constructed wetlands planted with emergent and submerged macrophytes were investigated. PS-MPs enhanced N removal efficiencies temporarily, whereas the N removal rate constants were declined as exposure time was prolonged. The NH4+-N removal rate constants declined by 25.78 % and 34.03 % in E and S groups respectively. The NO3--N removal rate constants declined by 22.13 % in the S groups. Denitrifiers including Thiobacillus, Rhodobacter, and Sulfuritalea were stressed. The sensory quality deteriorated after PS-MPs exposure, which was significantly related to changes in Chlorophyll a, particle size distribution, and colored dissolved organic matter. Turbidity in E groups and chroma in S groups were greatly affected by PS-MPs. Overall, under MPs exposure, macrophytes in E groups were more suitable for nitrogen removal, and macrophytes in S groups better purified the turbidity. The study could provide the basis for better allocation of macrophytes in CWs to reduce the purifying risk by PS-MPs disturbance.

The Effect of Rifapentine and Rifampicin on Serum Voriconazole Levels Persist for 5 Days and 7 Days or More After Discontinuation in Tuberculosis Patients with Chronic Pulmonary Aspergillosis.

Purpose: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine. Patients and Methods: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses. Results: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (>70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine. Conclusion: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.

Combinatorial Biosynthesis Creates a Novel Aglycone Polyether with High Potency and Low Side Effects Against Bladder Cancer.

Polyethers play a crucial role in the development of anticancer drugs. To enhance the anticancer efficacy and reduce the toxicity of these compounds, thereby advancing their application in cancer treatment, herein, guided by the structure-activity relationships of aglycone polyethers, novel aglycone polyethers are rationally redesigned with potentially improved efficacy and reduced toxicity against tumors. To realize the biosynthesis of the novel aglycone polyethers, the gene clusters and the post-polyketide synthase tailoring pathways for aglycone polyethers endusamycin and lenoremycin are identified and subjected to combinatorial biosynthesis studies, resulting in the creation of a novel aglycone polyether termed End-16, which demonstrates significant potential for treating bladder cancer (BLCA). End-16 demonstrates the ability to suppress the proliferation, migration, invasion, and cellular protrusions formation of BLCA cells, as well as induce cell cycle arrest in the G1 phase in vitro. Notably, End-16 exhibits superior inhibitory activity and fewer side effects against BLCA compared to the frontline anti-BLCA drug cisplatin in vivo, thereby warranting further preclinical studies. This study highlights the significant potential of integrating combinatorial biosynthesis strategies with rational design to create unnatural products with enhanced pharmacological properties.

Reveling the micromolecular biological mechanism of acetate, thiosulfate and Fe0 in ecological floating beds for treating low C/N wastewater: Insight into nitrogen removals and greenhouse gases reductions.

Selecting an appropriate electron donor to enhance nitrogen removal for treating low C/N wastewater in ecological floating beds (EFBs) is controversy. In this study, a systematic and comprehensive evaluation of sodium acetate (EFB-C), sodium thiosulfate (EFB-S) and iron scraps (EFB-Fe) was performed in a 2-year experiment on long-term viability including nitrogen removal and greenhouse gas emissions associated with key molecular biological mechanisms. The results showed that EFB-C (43-85 %) and EFB-S (40-88 %) exhibited superior total nitrogen (TN) removal. Temperature and hydraulic retention time (HRT) have significant impacts on TN removal of EFB-Fe, however, it could reach 86 % under high temperature (30-35 °C) and a long HRT (3 days), and it has lowest N2O (0-6.2 mg m-2 d-1) and CH4 (0-5.3 mg m-2 d-1) fluxes. Microbial network analysis revealed that the microbes changed from competing to cooperating after adding electron donors. A higher abundance of anammox genera was enriched in EFB-Fe. The Mantel's test and structural equation model provided proof of the differences, which showed that acetate and thiosulfate were similar, whereas Fe0 was different in the nitrogen removal mechanism. Molecular biology analyses further verified that heterotrophic, autotrophic, and mixotrophic coupled with anammox were the main TN removal pathways for EFB-C, EFB-S, and EFB-Fe, respectively. These findings provide a better understanding of the biological mechanisms for selecting appropriate electron donors for treating low C/N wastewater.

Identifying the differentially expressed peripheral blood microRNAs in psychiatric disorders: a systematic review and meta-analysis.

Background: Evidence has suggested that microRNAs (miRNAs) may play an important role in the pathogenesis of psychiatric disorders (PDs), but the results remain inconclusive. We aimed to identify specific differentially expressed miRNAs and their overlapping miRNA expression profiles in schizophrenia (SZ), major depression disorder (MDD), and bipolar disorder (BD), the three major PDs. Methods: The literatures up to September 30, 2023 related to peripheral blood miRNAs and PDs were searched and screened from multiple databases. The differences in miRNA levels between groups were illustrated by the standardized mean difference (SMD) and 95% confidence interval (95% CI). Results: In total, 30 peripheral blood miRNAs were included in the meta-analysis, including 16 for SZ, 12 for MDD, and 2 for BD, each was reported in more than 3 independent studies. Compared with the control group, miR-181b-5p, miR-34a-5p, miR-195-5p, miR-30e-5p, miR-7-5p, miR-132-3p, miR-212-3p, miR-206, miR-92a-3p and miR-137-3p were upregulated in SZ, while miR-134-5p, miR-107 and miR-99b-5p were downregulated. In MDD, miR-124-3p, miR-132-3p, miR-139-5p, miR-182-5p, miR-221-3p, miR-34a-5p and miR-93-5p were upregulated, while miR-144-5p and miR-135a-5p were downregulated. However, we failed to identify statistically differentially expressed miRNAs in BD. Interestingly, miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD. Conclusions: Our study identified 13 differentially expressed miRNAs in SZ and 9 in MDD, among which miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD by systematically analyzing qualified studies. These miRNAs may be used as potential biomarkers for the diagnosis of SZ and MDD in the future. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO, identifier CRD42023486982.

Diagnostic Utility of Surrounding Tissue Hardness in Breast Masses: A Quantitative Analysis Using Shear Wave Elastography to Distinguish Malignancy Across Various Mass Sizes.

Objective: This study aims to investigate the utility of shear wave elastography (SWE) in quantitatively assessing the surrounding tissue hardness of breast masses and its diagnostic significance in distinguishing between benign and malignant masses of varying sizes. Methods: A retrospective analysis was conducted on 60 patients with breast masses diagnosed at our hospital between January 1, 2022, and December 31, 2022. All patients underwent standard breast ultrasound examination and SWE assessment. Masses were categorized based on diameter (≤20mm and >20mm) for comparative analysis. SWE parameters, including maximum shear wave velocity (Max SWV), mean shear wave velocity (Mean SWV), and elasticity ratio (Eratio) of surrounding tissue, were recorded. Histopathological results determined mass nature. SWE parameters were correlated with pathological diagnoses for discrimination analysis. Results: Of all patients, 37 had benign masses, and 23 had malignant masses. Malignant masses exhibited significantly higher Max SWV, Mean SWV, and Eratio in surrounding tissue compared to benign masses (P < .05). Statistically significant differences in SWE parameters were observed between different-sized masses; smaller masses (≤20mm) showed higher SWE parameters in malignant masses compared to benign masses (P < .05). In masses larger than 20mm, though SWE parameters still differed between benign and malignant masses, the significance was less pronounced (P < .05). Receiver operating characteristic (ROC) analysis demonstrated higher diagnostic accuracy of SWE parameters in discriminating malignancy in smaller breast masses. Conclusions: SWE parameters effectively quantify surrounding tissue hardness in breast masses and have diagnostic value in distinguishing between benign and malignant masses of varying sizes, particularly in masses ≤20mm. SWE offers crucial quantitative parameters for the clinical discrimination of breast masses, enhancing diagnostic accuracy and sensitivity. Future studies should expand sample sizes and optimize diagnostic models to enhance SWE's utility further in discriminating breast mass malignancy.

Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.

Boosting the denitrification efficiency of iron-based constructed wetlands in-situ via plant biomass-derived biochar: Intensified iron redox cycle and microbial responses.

Considering the unsatisfied denitrification performance of carbon-limited wastewater in iron-based constructed wetlands (ICWs) caused by low electron transfer efficiency of iron substrates, utilization of plant-based conductive materials in-situ for improving the long-term reactivity of iron substrates was proposed to boost the Fe (III)/Fe (II) redox cycle thus enhance the nitrogen elimination. Here, we investigated the effects of withered Iris Pseudacorus biomass and its derived biochar on nitrogen removal for 165 days in ICWs. Results revealed that accumulate TN removal capacity in biochar-added ICW (BC-ICW) increased by 14.7 % compared to biomass-added ICW (BM-ICW), which was mainly attributed to the synergistic strengthening of iron scraps and biochar. The denitrification efficiency of BM-ICW improved by 11.6 % compared to ICWs, while its removal capacity declined with biomass consumption. Autotrophic and heterotrophic denitrifiers were enriched in BM-ICW and BC-ICW, especially biochar increased the abundance of electroactive species (Geobacter and Shewanella, etc.). An active iron cycle exhibited in BC-ICW, which can be confirmed by the presence of more liable iron minerals on iron scraps surface, the lowest Fe (III)/Fe (II) ratio (0.51), and the improved proportions of iron cycling genes (feoABC, korB, fhuF, TC.FEV.OM, etc.). The nitrate removal efficiency was positively correlated with the nitrogen, iron metabolism functional genes and the electron transfer capacity (ETC) of carbon materials (P < 0.05), indicating that redox-active carbon materials addition improved the iron scraps bioavailability by promoting electron transfer, thus enhancing the autotrophic nitrogen removal. Our findings provided a green perspective to better understand the redox properties of plant-based carbon materials in ICWs for deep bioremediation in-situ.

Resolvin and lipoxin metabolism network regulated by Hyssopus Cuspidatus Boriss extract in asthmatic mice.

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects.

Doxepin is more effective than zolpidem in improving executive function in patients with insomnia disorder.

BACKGROUND : Insomnia disorder is associated with an impairment in cognitive performance. Doxepin and zolpidem have been found to be effective in improving sleep. In this study, we aimed to compare the effects of doxepin and zolpidem on sleep structure and executive function in patients with insomnia disorder. METHODS: Patients with primary insomnia were randomly assigned to receive doxepin 6 mg/day orally or zolpidem 5-10 mg/day orally. Polysomnography (PSG) and the Pittsburgh Sleep Quality Index (PSQI) were used at baseline and after the 8-week treatment to compare clinical efficacy in the two groups. Safety was assessed using the Treatment Emergent Symptom Scale (TESS). Executive function was evaluated using the Wisconsin sorting card test (WSCT). RESULTS: Of 120 patients enrolled in the study, 60 participants were assigned to each group. A total of 109 participants (53 in the doxepin group and 56 in the zolpidem group) completed the study. After treatment, the wake after sleep onset (WASO) and total sleep time (TST) values in the doxepin group were 80.3 ± 21.4 min and 378.9 ± 21.9 min, respectively, which were significantly better than those in the zolpidem group (132.9 ± 26.5 min and 333.2 ± 24.2 min, respectively; (P < 0.05)). The sleep onset latency (SOL) value in the zolpidem group (20.3 ± 4.7 min) was significantly better than that in the doxepin group (28.2 ± 5.6 min; P < 0.05). The sleep efficiency (SE) in the doxepin group was 77.8 ± 4.2%, which was significantly better than that in the zolpidem group (68.6 ± 5.0%; P < 0.05). The PSQI score of the doxepin group was 6.1 ± 1.1, which was significantly lower than that in the zolpidem group (7.9 ± 1.9; P < 0.05). The treatment adverse events in the doxepin group was 23.3%, which was significantly higher than that in the zolpidem group (13.3%; P < 0.05). The WSCT showed a significant improvement in persistent errors (PE), random errors (RE), and categories in the two groups after 8-week treatment, and the improvement in RE and the categories was more obvious in the doxepin group (P < 0.05). CONCLUSIONS: Both doxepin and zolpidem were found to be effective in improving sleep quality, but the effects exhibited different patterns. Doxepin improved executive function more effectively than zolpidem in patients with insomnia disorder.

Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of COVID-19: A Meta-Analysis.

Introduction: Research shows the correlation between angiotensin-converting enzyme (ACE) deletion and insertion (D/I) polymorphism and COVID-19 risk; yet, conclusive evidence is still lacking. Thus, a meta-analysis of relevant articles was performed to more accurately estimate the relationship of ACE I/D polymorphism with the risk of COVID-19. Material and Methods. Relevant literature from the PubMed database was systematically reviewed, and odds ratios (ORs) and associated 95% confidence intervals (CIs) were measured. Additionally, the metapackage from Stata version 15.0 was used for statistical analysis. Results: The meta-analysis eventually contained 8 studies, including 1362 COVID-19 cases and 4312 controls. Based on the data, the ACE I/D polymorphism did not show an association with COVID-19 risk (D vs. I: OR = 1.25, 95% CI = 0.96-1.64; DD vs. II: OR = 1.89, 95% CI = 0.95-3.74; DI vs. II: OR = 1.75, 95% CI = 0.92-3.31; dominant model: OR = 1.88, 95% CI = 0.99-3.53; and recessive model: OR = 1.24, 95% CI = 0.81-1.90). Further, subgroup analyses stratified based on case proved that the ACE D allele demonstrated an association with increasing risk of COVID-19 severity (D vs. I: OR = 1.64, 95% CI = 1.01-2.66; DD vs. II: OR = 4.62, 95% CI = 2.57-8.30; DI vs. II: OR = 3.07, 95% CI = 1.75-5.38; dominant model: OR = 3.74, 95% CI = 2.15-6.50; and recessive model: OR = 1.28, 95% CI = 0.46-3.51). Conclusions: The ACE D allele was clearly related to an enhanced risk of COVID-19 severity. Hence, it is imperative to take into account the influence of genetic factors during the development of future vaccines.

Changes in the Metabolome and Nutritional Quality of Pulp from Three Types of Korla Fragrant Pears with Different Appearances as Revealed by Widely Targeted Metabolomics.

Korla fragrant pear (Pyrus sinkiangensis Yü) fruits have a unique flavor and are rich in phenolic acids, flavonoids, amino acids, and other nutrients. At present, the molecular basis of the quality differences among Korla fragrant pear fruits with a convex calyx and rough skin (RS), calyx shedding (SD), and a convex calyx (CV) remains unknown. To analyze the main metabolic components of Korla fragrant pear fruits and compare the antioxidant activities of these three fruits with different qualities, we used nutrient composition analysis and ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based widely targeted metabolomics approaches to analyze the changes in the quality characteristics of the pulp of these three Korla fragrant pear fruits with different appearances. The nutrient composition analysis showed that the fructose and glucose contents were not significantly different, and sucrose and vitamin C contents were significantly higher in SD fruits compared with CV and RS fruits. However, the levels of flavor substances such as titratable acids, total phenols, and total flavonoids were high in the pulp of RS fruits. The metabolomics results identified 1976 metabolites that were clustered into 12 categories, and phenolic acid and flavonoid metabolites were the most abundant. The differentially accumulated metabolites (DAMs) in the fruits with different appearances were screened by multivariate statistical methods, and a total of 595 DAMs were detected. The analysis identified 300 DAMs between the CV and SD fruits, 246 DAMs between the RS and CV fruits, and 405 DAMs between the RS and SD groups. SD fruits contained the most metabolites with a high relative content, especially phenolic acids, lipids, amino acids and derivatives, alkaloids, and organic acids. Compared with CV fruits, flavonoid metabolism was more active in RS fruits, which also had a higher content of flavonoids, whereas the fewest metabolites were found in CV fruits, which also displayed less flavonoid accumulation. KEGG pathway enrichment analysis revealed that the DAMs were mainly enriched in the metabolic pathways of flavone and flavonol biosynthesis, confirming that CV fruits have decreased flavone and flavonol biosynthesis and accumulate fewer flavonoids than RS fruits, which may explain the less bitter and astringent flavor of CV fruits. However, the flavonoid content in RS fruits was very high, which may be one of the reasons why RS fruits have a harder pulp and are less juicy, more slaggy, and less flavorful. Moreover, the analysis of the antioxidant activity showed that during fruit development and maturation, RS fruits had stronger antioxidant activity than SD and CV fruits. These results provide a theoretical basis for improving the fruit quality of Korla fragrant pears and the processing of pear pulp.

Evaluation of the impact of rifampicin on the plasma concentration of linezolid in tuberculosis co-infected patients.

Linezolid combined with rifampicin has shown excellent clinical outcomes against infection by multi-resistant Gram-positive bacteria. However, several studies have indicated that rifampicin reduces the plasma concentration of linezolid in patients with severe infection. Linezolid has been recommended for the treatment of patients with multidrug-resistant or extensively drug-resistant tuberculosis. However, studies on the interaction between linezolid and rifampicin in patients suffering from tuberculosis with infection are lacking. We evaluated the interaction between linezolid and rifampicin based on therapeutic drug monitoring (TDM). A retrospective analysis was undertaken for patients with tuberculosis and infection who were treated with linezolid and undergoing TDM. Patients were divided into the linezolid group and linezolid + rifampicin group. Data on demographic characteristics, disease, duration of linezolid therapy, and the plasma concentration of linezolid were used for statistical analyses. Eighty-eight patients with tuberculosis and infection were assessed. Values for the peak (Cmax) and trough (Cmin) concentrations of linezolid in plasma were available for 42 and 46 cases, respectively. Patients in the linezolid group had a significantly higher Cmax [15.76 (8.07-26.06) vs. 13.18 (7.48-23.64) mg/L, p = 0.048] and Cmin [8.38 (3.06-16.53) vs. 4.27 (0.45-10.47), p = 0.005] than those in the linezolid + rifampicin group. The plasma concentration of linezolid increased obviously in two patients after rifampicin discontinuation. However, the total efficiency and prevalence of hematologic adverse reactions were not significantly different in the linezolid group and linezolid + rifampin group. The plasma concentration of linezolid decreased upon combination with rifampicin, suggesting that TDM may aid avoidance of subtherapeutic levels of linezolid upon co-treatment with rifampicin.

Relationship between serum Th1/Th2 imbalance and depression in elderly patients with COPD and its clinical implications.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes organic damage as well as anxiety, depression, fear, and other psychological disorders, which seriously affect the quality of life and prognosis of patients and cause a huge economic burden to the family and society. OBJECTIVE: The aim of this study was to investigate the correlation between an imbalance of serum Th1/Th2 indicators and psychiatric depression in elderly patients with COPD and analyze its implications for clinical management. METHODS: From January 2018 to May 2022, 120 elderly patients with COPD treated at our hospital were categorized into two groups based on the self-rating depression scale (SDS): COPD with depression (SDS score ⩾ 50) and COPD alone (SDS score < 50). Blood gas analysis, pulmonary function, and serum Th1/Th2 index were determined. Receiver operating characteristic (ROC) curves were analyzed to explore the diagnostic value of serum Th1/Th2 ratios for COPD complicated by depression. RESULTS: Compared with the group without depression, the partial pressure of carbon dioxide and COPD assessment test scores were significantly higher, and the oxygenation index, forced expiratory volume in one second (FEV1), and percent predicted FEV1 were significantly lower in the COPD with depression group (P< 0.05). Interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were significantly higher in the COPD with depression group than in the group without depression (P< 0.05). Logistic regression analysis indicated that the imbalance of serum IL-1ß, IL-2, IL-6, IL-8, IL-10, and TNF-α was a risk factor for mental depression in elderly patients with COPD. When comparing prognostic indices, the interval before the first onset of clinically noticeable deterioration (CID-C) in the COPD with depression group was noticeably shorter than that in the COPD without depression group; the incidence of CID-C within 6 months was noticeably higher in the COPD with depression group than in the group without depression. CONCLUSION: Elderly patients with COPD and depression had reduced pulmonary function and higher serum Th1/Th2 levels, and an imbalance in serum Th1/Th2 indicators was a potential risk factor for depression. Moreover, elderly patients with COPD and depression were at a higher risk of disease progression and had a worse prognosis. Thus, an imbalance in serum Th1/Th2 indicators is a potential prognostic factor for evaluating depression in patients with COPD.

Effects of ferrous addition to Vallisneria natans: An attempt to apply ferrous to submerged macrophyte restoration.

Restoration of submerged macrophytes is an efficient way for endogenous nutrient control and aquatic ecological restoration, but slow growth and limited reproduction of submerged macrophytes still exist. In this research, the effect of ferrous on the seed germination and growth of Vallisneria natans (V. natans) were studied through aquatic simulation experiments and its influence on the rhizosphere microbial community was also explored. The seed germination, growth, and physiological and ecological parameters of V. natans were significantly affected by the ferrous treatments. Ferrous concentration above 5.0 mg/L showed significant inhibition of seed germination of V. natans and the best concentration for germination was 0.5 mg/L. During the growth of V. natans, after ferrous was added, a brief period of stress occurred, which then promoted the growth lasting for about 19 days under one addition. The diversity and richness of the rhizospheric microbial were increased after the ferrous addition. However, the function of the rhizospheric microbial community showed no significant difference between different concentrations of ferrous adding in the overlying water. Ferrous addition affected the growth condition of plants (content of CAT, Chl a, Chl b, etc.), thus indirectly affecting the rhizospheric microbial community of V. natans. These impacts on V. natans and rhizosphere microorganisms could generalize to other submerged macrophytes in freshwater ecosystems, particularly which have similar habits. These findings would contribute to the ecological evaluation of ferrous addition or iron-containing water, and provide a reference for submerged macrophytes restoration and ecological restoration in freshwater ecosystems.