Optimization of oral isavuconazole dose for population in special physiological or pathological state: a physiologically based pharmacokinetics model-informed precision dosing.

OBJECTIVE: To recommend precision dosing and improve therapeutic efficacy against invasive fungal disease, a physiologically based pharmacokinetic model (PBPK) of oral isavuconazole (ISA) was established and used to explore its disposition across populations in different physiological and pathological states. METHODS: Twenty-five pharmacokinetic (PK) studies of oral ISA were identified through a systematic search of PubMed. Concentration-time data were extracted using WebPlotDigitizer. Physiochemical parameters were obtained from published literature and DrugBank. Model development and simulation used the Simcyp population-based simulator, and visual predictive check and predictive error were used for the model evaluation. Probability of target attainment and the cumulative fraction of response analyses were performed for dose optimization. RESULTS: The developed PBPK model was successfully validated in different populations. Most predicted concentration-time points aligned with the observed data, with acceptable predictive errors for the critical parameters. We predicted the PK profiles and parameters of ISA in a population with severe hepatic impairment (HI), a population with obesity and paediatric patients aged 1 to less than 6 years old. The probability of target attainment and cumulative fraction of response analyses indicated that the population with severe HI should have half the maintenance dose. The population with obesity and population with severe HI should have a loading dose of 300 mg every 8 h for 2 days. For paediatric patients aged 1 to less than 6 years old, a weight-based dosing regimen (5.38 mg/kg) of ISA was suggested. CONCLUSION: The predicted value aligns with observations, suggesting ISA's potential predictability in PK profiles for other populations. The recommended dosing regimens increase our understanding of the use of ISA in special populations.

Nomogram for predicting the risk of nosocomial infections among obstetric inpatients: a large-scale retrospective study in China.

OBJECTIVE: This study aimed to develop and validate a nomogram for assessing the risk of nosocomial infections among obstetric inpatients, providing a valuable reference for predicting and mitigating the risk of postpartum infections. METHODS: A retrospective observational study was performed on a cohort of 28,608 obstetric patients admitted for childbirth between 2017 and 2022. Data from the year 2022, comprising 4,153 inpatients, were utilized for model validation. Univariable and multivariable stepwise logistic regression analyses were employed to identify the factors influencing nosocomial infections among obstetric inpatients. A nomogram was subsequently developed based on the final predictive model. The receiver operating characteristic (ROC) curve was utilized to calculate the area under the curve (AUC) to evaluate the predictive accuracy of the nomogram in both the training and validation datasets. RESULTS: The gestational weeks > = 37, prenatal anemia, prenatal hypoproteinemia, premature rupture of membranes (PROM), cesarean sction, operative delivery, adverse birth outcomes, length of hospitalization (days) > 5, CVC use and catheterization of ureter were included in the ultimate prediction model. The AUC of the nomogram was 0.828 (0.823, 0.833) in the training dataset and 0.855 (0.844, 0.865) in the validation dataset. CONCLUSION: Through a large-scale retrospective study conducted in China, we developed and independently validated a nomogram to enable personalized postpartum infections risk estimates for obstetric inpatients. Its clinical application can facilitate early identification of high-risk groups, enabling timely infection prevention and control measures.

Spatial distribution and priority conservation areas identification in Three-River-Source National Park considering the multifaceted values of plants.

Spatially differentiated conservation effort for natural resources is critical to achieving a balance between protection and development in national parks. However, the extent of priority conservation areas for plants that integrate multispecies and multifaceted values is unclear. Here, we selected fine-resolution environmental variables with stronger impacts on wild plant survival to spatialize the distribution of all modeling-eligible species using species distribution models in Three-River-Source National Park, China. These were then combined with in situ conservation results for insufficient data species to identify priority conservation areas (PCAs) in terms of diversity, ecological and economic values, respectively. We analyzed the spatial characteristics of the priority conservation areas and searched for conservation gaps not covered by national nature reserves. The results showed that this study obtained more precise results on the spatial distribution of species by improving environmental variables and upgrading the spatial resolution. In Three-River-Source National Park, the species richness of wild plants showed a decreasing trend from southeast to northwest. There were significant differences in the spatial distribution of the priority conservation areas identified based on the three values, which was the basis for the spatially differentiated conservation and development of wild plant resources. In addition, the priority conservation areas obtained based on ecological value found Top17% priority conservation areas in the Hoh Xil Natural Reserve, which could not be revealed based on diversity or economic value. These results highlight the urgency of implementing multispecies and multifaceted values studies in national parks. In the future, studying conflicts between wildlife priority conservation areas and human activities, and expanding to national parks on a global scale, will be the focus that this study will continue to explore.

A physiologically based pharmacokinetic analysis to predict the pharmacokinetics of intravenous isavuconazole in patients with or without hepatic impairment.

Isavuconazole (ISA) is an azole antifungal used in the treatment of invasive aspergillosis and mucormycosis. Patients with mild and moderate hepatic impairment have lower clearance (CL) as compared to the healthy population. Currently, there is no data on ISA in patients with severe hepatic impairment (Child-Pugh Class C). The purpose of this study was to build a physiologically based pharmacokinetic (PBPK) model to describe the pharmacokinetics (PK) of intravenous ISA, and to predict changes in ISA disposition in different patient populations and in patients with hepatic impairment to guide personalized dosing. By incorporating the systemic and drug specific parameters of ISA, the model was initially developed in healthy population and validated with 10 independent PK profiles obtained from healthy subjects and from patients with normal liver function. The results showed a satisfactory predictive capacity, with most of the relative predictive errors being between ±30% for area under the curve (AUC) and Cmax The observed plasma concentration-time profiles of ISA were well described by the model predicted profiles. The model adequately predicted the reduced CL of ISA in patients with mild and moderate hepatic impairment. Furthermore, the model predicted a decrease in CL of about 60% in patients with severe hepatic impairment. Therefore, we recommend reducing the dose by 50% in patients with severe hepatic impairment. The model also predicted differences in the PK of ISA between Caucasian and Asian population, with the CL ratio of 0.67 in Chinese vs Caucasian population. The developed PBPK model of ISA provides a reasonable approach for optimizing the dosage regimen in different ethnic populations and in patients with severe hepatic impairment.

Impact assessment of urbanization on vegetation net primary productivity: A case study of the core development area in central plains urban agglomeration, China.

Rapid urbanization process has a negative or positive impact on vegetation growth. Net primary productivity (NPP) is an effective indicator to characterize vegetation growth status. Taking the core development area of the Central Plains urban agglomeration as the study area, we estimated the NPP and its change trend in the past four decades using the Carnegie-Ames-Stanford Approach (CASA) model and statistical analysis based on meteorological and multi-source remote sensing data. Meanwhile, combined with the urbanization impact framework, we further analyzed urbanization's direct and indirect impact on NPP. The results showed that the urban area increased by 2688 km2 during a high-speed urbanization process from 1983 to 2019. As a result of the intense urbanization process, a continuous NPP decrease (direct impact) can be seen, which aggravated along with the acceleration of the urban expansion, and the mean value of direct impact was 130.84 g C·m-2·a-1. Meanwhile, urbanization also had a positive impact on NPP (indirect impact). The indirect impact showed an increasing trend during urbanization with a mean value of 10.91 g C·m-2·a-1. The indirect impact was mainly related to temperature in climatic factors. The indirect impact has a seasonal heterogeneity, and high-temperature environments of urban areas are more effective in promoting vegetation growth in autumn and winter than in summer. Among different cities, high-speed development cities have higher indirect impact values than medium's and low's because of better ecological construction. This study is of great significance for understanding the impact of urbanization on vegetation growth in the Central Plains urban agglomeration area, supporting urban greening plans, and building sustainable and resilient urban agglomerations.

A Glove-Wearing Detection Algorithm Based on Improved YOLOv8.

Wearing gloves during machinery operation in workshops is essential for preventing accidental injuries, such as mechanical damage and burns. Ensuring that workers are wearing gloves is a key strategy for accident prevention. Consequently, this study proposes a glove detection algorithm called YOLOv8-AFPN-M-C2f based on YOLOv8, offering swifter detection speeds, lower computational demands, and enhanced accuracy for workshop scenarios. This research innovates by substituting the head of YOLOv8 with the AFPN-M-C2f network, amplifying the pathways for feature vector propagation, and mitigating semantic discrepancies between non-adjacent feature layers. Additionally, the introduction of a superficial feature layer enriches surface feature information, augmenting the model's sensitivity to smaller objects. To assess the performance of the YOLOv8-AFPN-M-C2f model, this study conducted multiple experiments using a factory glove detection dataset compiled for this study. The results indicate that the enhanced YOLOv8 model surpasses other network models. Compared to the baseline YOLOv8 model, the refined version shows a 2.6% increase in mAP@50%, a 63.8% rise in FPS, and a 13% reduction in the number of parameters. This research contributes an effective solution for the detection of glove adherence.

External evaluation of population pharmacokinetic models for voriconazole in Chinese adult patients with hematological malignancy.

OBJECTIVES: Patients with hematological malignancies are prone to invasive fungal disease due to long-term chemotherapy or radiotherapy. Voriconazole is a second-generation triazole broad-spectrum antibiotic used to prevent or treat invasive fungal infections. Many population pharmacokinetic (pop PK) models have been published for voriconazole, and various diagnostic methods are available to validate the performance of these pop PK models. However, most of the published models have not been strictly evaluated externally. The purpose of this study is to evaluate these models externally and assess their predictive capabilities. METHODS: The external dataset consists of adults receiving voriconazole treatment at Fujian Medical University Union Hospital. We re-established the published models based on their final estimated values in the literature and used our external dataset for initial screening. Each model was evaluated based on the following outcomes: prediction-based diagnostics, prediction- and variability-corrected visual predictive check (pvcVPC), normalized prediction distribution errors (NPDE), and Bayesian simulation results with one to two prior observations. RESULTS: A total of 237 samples from 166 patients were collected as an external dataset. After screening, six candidate models suitable for the external dataset were finally obtained for comparison. Among the models, none demonstrated excellent predictive performance. Bayesian simulation shows that all models' prediction precision and accuracy were significantly improved when one or two prior concentrations were given. CONCLUSIONS: The published pop PK models of voriconazole have significant differences in prediction performance, and none of the models could perfectly predict the concentrations of voriconazole for our data. Therefore, extensive evaluation should precede the adoption of any model in clinical practice.

Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation.

PURPOSE: This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: We included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 in this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared. RESULTS: After the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no significant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios. CONCLUSION: POS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.

ZEB1 modulates endometrial receptivity through epithelial-mesenchymal transition in endometrial epithelial cells in vitro.

Zinc finger E-box binding homeobox 1 (ZEB1) promotes epithelial-mesenchymal transition (EMT) in carcinogenesis, but its role in embryo implantation has not yet been identified. The present study sought to verify if ZEB1 plays a role in endometrial receptivity through regulation of EMT during embryo implantation. Endometrial epithelium from sixty patients in phase of the menstrual cycle (including proliferative and secretory phases) were collected for assessment of mRNA/protein expression. In human endometrial adenocarcinoma cell line RL95-2, ZEB1 expression was suppressed by using shRNA, and the cell function and mRNA/protein expression were evaluated. RL95-2 cells and human choriocarcinoma cell line JAR were co-cultured to establish embryo implantation model in vitro. The results showed that, ZEB1 was highly expressed at both mRNA and protein levels in human endometrium during mid-secretory phase of the menstrual cycle. Knockdown of ZEB1 expression in RL95-2 cells attenuated cell growth, migration, DNA replication, and altered expression of E-cadherin and vimentin at both mRNA and protein levels. Interestingly, knockdown of ZEB1 expression in RL95-2 cells potently suppressed JAR spheroid attachment in vitro (P < 0.01). Additionally, the. Conclusively, knockdown of ZEB1 suppressed embryo implantation in vitro, paralleled with alteration of EMT markers. ZEB1 is likely to modulate endometrial receptivity through promotion of EMT, that could be crucial for embryo implantation process.

Utility evaluation of HLA-B*13:01 screening in preventing trichloroethylene-induced hypersensitivity syndrome in a prospective cohort study.

OBJECTIVES: Trichloroethylene (TCE) -induced hypersensitivity syndrome (TIHS) is a potentially life-threatening disease. Several genetic susceptibility biomarkers have been found to be associated with TIHS, and this systematic prospective study has been conducted to evaluate the utility of these genetic susceptibility biomarkers in preventing the disease. METHODS: The newly hired TCE-exposed workers were recruited from March 2009 to October 2010. HLA-B*13:01 genotyping and 3-month follow-up procedure were conducted. All workers were monitored for adverse reaction by telephone interview every week. The workers with early symptoms of TIHS were asked to go to the hospital immediately for further examination, diagnosis and treatment. The medical expense record data of patients with TIHS were collected for cost-effectiveness analysis in 2018. RESULTS: Among 1651 workers, 158 (9.57%) were found to carry the HLA-B*13:01 allele and 16 (0.97%) were diagnosed with TIHS. HLA-B*13:01 allele was significantly associated with an increased TIHS risk (relative risk=28.4, 95% CI 9.2 to 86.8). As a risk predictor of TIHS, HLA-B*13:01 testing had a sensitivity of 75%, a specificity of 91.1% and an area under curve of 0.83 (95% CI 0.705 to 0.955), the positive and negative predictive values were 7.6% and 99.7%, respectively. The incidence of TIHS was significantly decreased in HLA-B*13:01 non-carriers (0.27%) compared with all workers (0.97%, p=0.014). Cost-effectiveness analysis showed that HLA-B*13:01 screening could produce an economic saving of $4604 per TIHS avoided. CONCLUSIONS: Prospective HLA-B*13:01 screening may significantly reduce the incidence of TIHS and could be a cost effective option for preventing the disease in TCE-exposed workers.

A multi-center study on the risk factors of infection caused by multi-drug resistant Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii (AB) is critical for healthcare-associated infections (HAI) with significant regional differences in the resistance rate, but its risk factors and infection trends has not been well studied. We aimed to explore the risk factors, epidemiological characteristics and resistance of multidrug-resistant Acinetobacter baumannii (MDR-AB) in intensive care unit inpatients. METHODS: Data of patients with MDR-AB (195 cases), and with antibiotic-sensitive AB infection (294 cases, control) during January to December, 2015 in three medical centers in Xiamen, China were conducted and analyzed in the present retrospective study. RESULTS: Lower respiratory tract infection with AB accounted for 68.71%. MDR-AB was detected in 39.88% of all cases. Univariate analysis suggested that mechanical ventilation, indwelling catheter, cancer patients, length of hospitalization in intensive care unit (ICU) ≥15 d, Acute Physiology and Chronic Health Evaluation (APACHE) II score, combined using antibiotic before isolation of AB and use of third-lines cephalosporins were associated with the development of MDR-AB healthcare-associated infections. Dose-response relationship analysis suggested that the age and the days of mechanical ventilation were associated with increased infection with MDR-AB. Logistic regression analysis suggested that, mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter, were associated with MDR-AB infection, with odds ratios (OR) and 95% confidence intervals (CI) of 3.93 (1.52-10.14), 4.11 (1.58-10.73), and 4.15 (1.32-12.99), respectively. CONCLUSIONS: MDR-AB infection was associated with mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter. Furthermore, the age and the days of mechanical ventilation were associated with increased infection with MDR-AB.

Characterisation of dissolved organic matter in stormwater using high-performance size exclusion chromatography.

Understanding the complexity of dissolved organic matter (DOM) in stormwater has drawn a lot of interest, since DOM from stormwater causes not only environmental impacts, but also worsens downstream aquatic quality associated with water supply and treatability. This study introduced and employed high-performance size exclusion chromatography (HPSEC) coupled with an ultraviolet-visible (UV-vis) diode array detector to assess changes in stormwater-associated DOM characteristics. Stormwater DOM was also analysed in relation to storm event characteristics, water quality and spectroscopic analysis. Statistical tools were used to determine the correlations within DOM and water quality measurements. Results showed that dissolved organic carbon (DOC) and UV absorbance at 254 nm (UV254) as conventional DOM parameters were found to be correlated well to the changes in stormwater quality during each of the three storm events studied. Both detector wavelengths (210 and 254 nm) and their ratio (A210/A254) were found to provide additional information on the physiochemical properties of stormwater-associated DOM. This study indicated that A210/A254 is an important parameter which could be used to estimate the DOM proportions of functional groups and conjugated carbon species. This study provided also an understanding of stormwater quality constituents through assessing variability and sensitivity for various parameters, and the additional information of rainfall characteristics on runoff quality data for a better understanding of parameter correlations and influences.

High-performance size exclusion chromatography with a multi-wavelength absorbance detector study on dissolved organic matter characterisation along a water distribution system.

This study examined the associations between dissolved organic matter (DOM) characteristics and potential nitrification occurrence in the presence of chloramine along a drinking water distribution system. High-performance size exclusion chromatography (HPSEC) coupled with a multiple wavelength detector (200-280nm) was employed to characterise DOM by molecular weight distribution, bacterial activity was analysed using flow cytometry, and a package of simple analytical tools, such as dissolved organic carbon, absorbance at 254nm, nitrate, nitrite, ammonia and total disinfectant residual were also applied and their applicability to indicate water quality changes in distribution systems were also evaluated. Results showed that multi-wavelength HPSEC analysis was useful to provide information about DOM character while changes in molecule weight profiles at wavelengths less than 230nm were also able to be related to other water quality parameters. Correct selection of the UV wavelengths can be an important factor for providing appropriate indicators associated with different DOM compositions. DOM molecular weight in the range of 0.2-0.5kDa measured at 210nm correlated positively with oxidised nitrogen concentration (r=0.99), and the concentrations of active bacterial cells in the distribution system (r=0.85). Our study also showed that the changes of DOM character and bacterial cells were significant in those sampling points that had decreases in total disinfectant residual. HPSEC-UV measured at 210nm and flow cytometry can detect the changes of low molecular weight of DOM and bacterial levels, respectively, when nitrification occurred within the chloraminated distribution system.

[Association of CYP2C19 gene polymorphisms with long-term recurrent risk of ischemic stroke among ethnic Han Chinese from Fujian].

OBJECTIVE: To assess the association of genetic polymorphisms of CYP2C19*2,*3,*17 with the recurrence risk of ischemic stroke during clopidogrel prevention in ethnic Han Chinese from Fujian Province. METHODS: Clinical data of 985 patients with acute ischemic stroke was collected. After 1 year postdischarge follow-up evaluations, only 114 patients with persistence of clopidogrel were enrolled. CYP2C19 genetic polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and direct sequencing ,then we analysis the correlation between polymorphisms and the recurrence of stroke. RESULTS: Among the 114 patients, 23 had a second onset whilst receiving clopidogrel treatment. During the antiplatelet therapy with clopidogrel, carriers of CYP2C19 poor metabolizer (CYP2C19*2/*2 or *2/*3) had a higher rate of recurrent stroke compared with extensive metabolizers (CYP2C19*1/*1) (OR=4.71, 95%CI: 1.18-18.80, P<0.05). Carriers of CYP2C19 *2 mutant allele had increased recurrence compared with those carrying none loss-of-function allele (OR=2.31, 95%CI: 1.20-4.46, P<0.05). The rate of recurrent stroke in those carrying homozygous mutant *2 allele (CYP2C19*2/*2) was 6.14 times greater than the rate of wild-type homozygotes (CYP2C19*1/*1) (95%CI: 1.54-24.54, P<0.05). Patients with previous stroke history had increased risk of recurrence (OR= 4.146, 95%CI: 1.259-13.655, P<0.05). However, CYP2C19*17 was not detected in the group. CONCLUSION: For ethnic Han Chinese patients receiving clopidogrel treatment, carriers of poor metabolizer or homozygous mutant *2 allele (CYP2C19*2/*2) have a higher risk of recurrent stroke. The CYP2C19 *2 allele is an independent risk factor for recurrent stroke. Those with previous history of stroke are more prone to the recurrence.

Hepatic infarction occurred after 125I particle stent treatment for hepatocellular carcinoma with portal vein tumor thrombus: A case report.

BACKGROUND: Hepatic infarction is a rare liver condition. The purpose of this study is to report a case of hepatic infarction caused by thrombus formation following portal vein stent implantation in a patient with hepatocellular carcinoma and portal vein tumor thrombus, and to explore the underlying causes. CASE REPORT: The patient in this study was a 52-year-old male admitted with diffuse hepatocellular carcinoma involving the right lobe and portal vein tumor thrombus. After undergoing portal vein stent implantation and 125I particle strand implantation treatment, the portal vein was patent, and the pressure decreased. However, multiple instances of hepatic artery chemoembolization combined with targeted immunotherapy resulted in gradual reduction in the diameter of the hepatic artery and affecting hepatic arterial blood flow. Two months post-stent implantation, thrombus formation within the stent was noted, and the patient's condition did not improve with anticoagulant therapy, as evidenced by follow-up CT scans showing an increase in thrombi. Six months later, the patient suffered from gastrointestinal bleeding and, despite emergency esophagogastric variceal ligation and hemostatic treatment, developed hepatic parenchymal infarction and liver function failure. CONCLUSIONS: We reveal the underlying cause is that (1) thrombus formation within the portal vein stent, leading to portal vein embolism and obstructed blood flow due to exacerbate portal hypertension after various treatments; and (2) the effect of hepatic artery chemoembolization, immunotherapy, and targeted therapy on tumor angiogenesis, causing reduced hepatic artery diameter and impaired arterial blood flow. These factors disrupt the liver's dual blood supply system, ultimately contributing to hepatic infarction. To our knowledge, this is the first report of hepatic infarction as a complication following portal vein stent implantation for hepatocellular carcinoma with portal vein tumor thrombus, and it holds significant reference value for guiding the treatment of hepatocellular carcinoma with concurrent portal vein tumor thrombus in a clinical setting.

Chromosome-scale reference genome of broccoli (Brassica oleracea var. italica Plenck) provides insights into glucosinolate biosynthesis.

Broccoli (Brassica oleracea var. italica Plenck) is an important vegetable crop, as it is rich in health-beneficial glucosinolates (GSLs). However, the genetic basis of the GSL diversity in Brassicaceae remains unclear. Here we report a chromosome-level genome assembly of broccoli generated using PacBio HiFi reads and Hi-C technology. The final genome assembly is 613.79 Mb in size, with a contig N50 of 14.70 Mb. The GSL profile and content analysis of different B. oleracea varieties, combined with a phylogenetic tree analysis, sequence alignment, and the construction of a 3D model of the methylthioalkylmalate synthase 1 (MAM1) protein, revealed that the gene copy number and amino acid sequence variation both contributed to the diversity of GSL biosynthesis in B. oleracea. The overexpression of BoMAM1 (BolI0108790) in broccoli resulted in high accumulation and a high ratio of C4-GSLs, demonstrating that BoMAM1 is the key enzyme in C4-GSL biosynthesis. These results provide valuable insights for future genetic studies and nutritive component applications of Brassica crops.

Pharmacological Mechanism of Chinese Medicine in Systemic Lupus Erythematosus: A Narrative Review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.

Pathogen distribution and infection patterns in pediatric severe pneumonia: A targeted next-generation sequencing study.

OBJECTIVE: Severe pneumonia in children represents a significant clinical challenge due to its high incidence and associated mortality. This study aimed to assess the distribution of pathogens and patterns of infection in pediatric patients with severe pneumonia. METHODS: This study included 110 pediatric patients diagnosed with severe pneumonia, who were admitted to Guangxi Maternal and Child Health Hospital between July 2021 and November 2023. Pathogen-targeted next-generation sequencing (tNGS) was employed to identify respiratory pathogens in these cases. RESULTS: Pathogens were detected in 109 out of 110 cases, yielding a positive detection rate of 99.09%. Among these cases, 25 (22.72%) involved single-pathogen infections, while 84 (76.36%) were characterized by mixed infections. The infection pattern in children with severe pneumonia was relatively common with bacterial-viral coinfection (28.2%, 31/110). A total of 39 pathogens were identified from the 110 children with severe pneumonia, with the top three pathogens being Mycoplasma pneumoniae (30.91%, 34/110), Human Respiratory Syncytial Virus Type A (26.36%, 29/110), and Human Herpesvirus (18.18%, 20/110). Notably, 38.2% (13/34) of the cases were found to have macrolide-resistant Mycoplasma pneumoniae (MRMP). Additionally, 40% (44/110) of the children required admission to the intensive care unit (ICU). CONCLUSION: The application of tNGS demonstrates significant utility in the detection of pathogens in pediatric patients with severe pneumonia. The predominant pathogens identified in this study are Mycoplasma pneumoniae, Human Respiratory Syncytial Virus, and Human Herpesvirus. Furthermore, mixed infections involving multiple pathogens were observed in 76.36% of the cases, and a substantial proportion (40%) of these patients necessitated intensive care.

Spatiotemporal variation of irrigation water requirements for grain crops under climate change in Northwest China.

Clarifying the spatiotemporal variation of crop irrigation water requirement (IWR) under the background of climate change is an essential basis for water resource management, determining the irrigation quota and adjusting the planting structure. Using 61 years of climate data from 205 stations in Northwest China, this study investigated the spatiotemporal variations of climatic factors and IWR during the growth period of five main grain crops (spring wheat, winter wheat, spring maize, summer maize, and rice) and explored the dominant climatic driving factors of IWR variation. Results showed that (1) the IWR of grain crops showed distinct differences. Rice was the highest water consumption crop (mean of 753.78 mm), and summer maize was the lowest (mean of 452.90 mm). (2) The variation trends and average values of IWR of different grain crops have spatial heterogeneity across Northwest China. For most crops, high values and increasing trends of IWR were mainly located in eastern Xinjiang, western Gansu, and western Inner Mongolia. (3) Tmax (maximum temperature), Tmin (minimum temperature), and Peff (effective precipitation) showed an increasing trend during the growth period of each grain crop, while U10 (wind speed at 10 m height), SD (solar radiation), and RH (relative humidity) presented decreasing trends. (4) SD, Tmax, and U10 promoted the increase of grain crops' IWR, while Peff and RH inhibited it. The impacts of climatic factors on the grain crop IWR differed among different regions. Peff was the most influential factor to the IWR of all grain crops in most areas. Therefore, under the premise of a significant increase in T and uncertain precipitation mode in the future, it is urgent to take effective water-saving measures according to the irrigation needs of the region. To cope with the adverse impact of climate change on the sustainable development of agriculture in the northwest dry area, to ensure regional and national food security.

Spatiotemporal variations and its driving factors of NDVI in Northwest China during 2000-2021.

Northwest China (WTL) is an essential ecological barrier zone of China, an important node of the "Silk Road Economic Belt," and a crucial bearing area for China's execution of the "One Road and One Belt" and "Going Global" strategies. However, its ecology is exceedingly fragile and particularly vulnerable to climate change and human interference. This study explored the spatiotemporal evolution characteristics of vegetation in WTL using NDVI data and investigated its drive mechanisms by geodetector, partial correlation analysis, and residual trend analysis methods. As well as forecasting the trend for vegetation changes. The findings demonstrated that (1) the change in NDVI manifested an overall improvement trend and the distribution in space of NDVI rose from the center to the periphery. 57.07% of the area had a sparse cover of vegetation (NDVI between 0 and 0.2). In addition, about 49% of regions had deterioration tendencies, which were mainly aggregated in HX, QCXDB, QCXDN, and the eastern of QCXQN and QCXXB. (2) The NDVI's shifting trend was unsustainability, and the region of uncertain future accounted for 57.45% of the total, with apparent unsustainability features. (3) The key parameters influencing NDVI spatial distribution were Pre (precipitation), vegetation type, land use type, and soil type. The interaction between two factors enhanced the influence of any single element, which appeared as bivariate and nonlinear enhancements. (4) Both climate variations and human activities have been recognized as key variables affecting NDVI growth. NDVI variance in 73.02% of areas was influenced by the combined effects of climate variations and human activities. However, human activities were the most influential element in NDVI growth, with the relative contributions of 80.28% (19.72% of which was caused by climate variations). These results can be conducive to deepening insights into the local vegetation status, identifying the mechanisms driving vegetation change, and providing scientific recommendations for WTL's ecosystem restoration measures based on actual situations.