[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

ODF3B affects the proliferation and apoptosis of glioma via the JAK/STAT pathway.

The pathogenesis of glioma has remained unclear. In this study, it was found that high expression of the outer dense fibers of sperm tail 3B (ODF3B) in gliomas was positively correlated with the grade of glioma. The higher the grade, the worse the prognosis. ODF3B is closely related to the growth and apoptosis of glioma. In terms of mechanism, ODF3B was found to affect the proliferation and apoptosis of glioma through the JAK1 and JAK2/STAT3 pathways. ODF3B was also found to affect the growth and apoptosis of glioma in vivo. We conclude that ODF3B affects glioma proliferation and apoptosis via the JAK/STAT pathway and is a potential therapeutic target.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening.

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

Revolutionizing lymph node metastasis imaging: the role of drug delivery systems and future perspectives.

The deployment of imaging examinations has evolved into a robust approach for the diagnosis of lymph node metastasis (LNM). The advancement of technology, coupled with the introduction of innovative imaging drugs, has led to the incorporation of an increasingly diverse array of imaging techniques into clinical practice. Nonetheless, conventional methods of administering imaging agents persist in presenting certain drawbacks and side effects. The employment of controlled drug delivery systems (DDSs) as a conduit for transporting imaging agents offers a promising solution to ameliorate these limitations intrinsic to metastatic lymph node (LN) imaging, thereby augmenting diagnostic precision. Within the scope of this review, we elucidate the historical context of LN imaging and encapsulate the frequently employed DDSs in conjunction with a variety of imaging techniques, specifically for metastatic LN imaging. Moreover, we engage in a discourse on the conceptualization and practical application of fusing diagnosis and treatment by employing DDSs. Finally, we venture into prospective applications of DDSs in the realm of LNM imaging and share our perspective on the potential trajectory of DDS development.

Short-term resistance training combined with cheese supplementation can optimize body parameters and intestinal microbiota in healthy adults.

Background: Resistance training (RT) and protein supplementation have beneficial effects on the human body. However, it is unknown if RT's health-promoting benefits are enhanced by food-borne protein, such as cheese supplements. This study investigated at how the body composition, lipid profile, muscle strength and intestinal microbiota changed following four weeks of RT combined with cheese supplementation. Methods: Thirty-five male and untrained adults were divided into 4 groups [control group (CON), low-dose group (LG), medium-dose group (MG), and high-dose group (HG)] and underwent a 4-week RT (3 times/week) in combination with cheese supplementation. Participants received 108 g (LG), 216 g (MG), or 324 g (HG) of cheese on the day of RT, and each serving (108 g) of cheese contained 6.7 g of food-borne protein. The RT program was a whole-body program with movements such as chest presses, leg presses, seated rowing, knee extensions and triceps pushdown. The exercise consisted of 3 sets of 8-12 repetitions at 70%RM, with a 120-s break in between. Body parameters (body composition, lipid profile and muscle strength) were assessed at baseline and after the 4 weeks of the intervention. The feces sample was taken every weekend. A two-way (group × time) mixed-design ANOVA was used to examine the body parameters. Independent one-way ANOVA was used to analyze the differences between groups in baseline characteristics and different values of each parameter. Results: HDL-C level was higher in MG than in LG. In comparison to LG, MG had lower levels of total cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, body fat mass and body fat percentage. However, there was no difference in muscle strength between in the four groups. The abundance of Actinobacteria was higher in LG and Erysipelotrichaceae was lower in MG and HG. Conclusion: The findings suggest that cheese could be a readily available food-borne protein supplement to enhance the beneficial effects of RT on health. It may improve body composition and lipid profile by altering the proportion of intestinal microbiota. During the 4-week RT intervention, 13.4 g of foodborne protein in the form of cheese 3 times per week was the ideal dosage.

STING inhibition alleviates bone resorption in apical periodontitis.

AIM: The goal of this study was to investigate the potential effects of an immunotherapeutic drug targeting STING to suppress the overreactive innate immune response and relieve the bone defect in apical periodontitis. METHODOLOGY: We established an apical periodontitis mouse model in Sting-/- and WT mice in vivo. The progression of apical periodontitis was analysed by micro-CT analysis and H&E staining. The expression level and localization of STING in F4/80+ cells were identified by IHC and immunofluorescence staining. RANKL in periapical tissues was tested by IHC staining. TRAP staining was used to detect osteoclasts. To clarify the effect of STING inhibitor C-176 as an immunotherapeutic drug, mice with apical periodontitis were treated with C-176 and the bone loss was identified by H&E, TRAP, RANKL staining and micro-CT. Bone marrow-derived macrophages (BMMs) were isolated from Sting-/- and WT mice and induced to osteoclasts in a lipopolysaccharide (LPS)-induced inflammatory environment in vitro. Moreover, WT BMMs were treated with C-176 to determine the effect on osteoclast differentiation by TRAP staining. The expression levels of osteoclast-related genes were tested using qRT-PCR. RESULTS: Compared to WT mice, the bone resorption and inflammatory cell infiltration were reduced in exposed Sting-/- mice. In the exposed WT group, STING was activated mainly in F4/80+ macrophages. Histological staining revealed the less osteoclasts and lower expression of osteoclast-related factor RANKL in Sting-/- mice. The treatment of the STING inhibitor C-176 in an apical periodontitis mice model alleviated inflammation progression and bone loss, similar to the effect observed in Sting-/- mice. Expression of RANKL and osteoclast number in periapical tissues were also decreased after C-176 administration. In vitro, TRAP staining showed fewer positive cells and qRT-PCR reflected decreased expression of osteoclastic marker, Src and Acp5 were detected during osteoclastic differentiation in Sting-/- and C-176 treated BMMs. CONCLUSIONS: STING was activated and was proven to be a positive factor in bone loss and osteoclastogenesis in apical periodontitis. The STING inhibitor C-176 administration could alleviate the bone loss via modulating local immune response, which provided immunotherapy to the treatment of apical periodontitis.

A MOF-derived flower-shaped CeCo-oxide as a multifunctional material for high-performance lithium-ion batteries and supercapacitors.

Precursor method is a well-known technology for preparing certain functional materials. In this work, a novel 3d-4f bimetallic organic framework, denoted as 45MCeCo (45 M representing 4,5-imidazole dicarboxylic acid), was successfully synthesized via a hydrothermal technique. The compound thus obtained has the molecular formula of C10H11CeCoN4O12. By meticulously controlling the amounts of the experimental materials, it was feasible to prepare flower-like crystals possessing identical single crystal structures and significantly larger specific surface areas. As a precursor for electrode materials, this structure underwent calcination at different temperatures to prepare Co3O4/CeO2 composites with in situ composite heterostructures. Post-electrochemical tests revealed that CeO2 remains unreactive across all potentials, thereby contributing to the stabilization of the electrode material structure. In contrast, Co3O4 participated in redox reactions to provide a specific capacity to the sample. In addition, when comparing the performance of the electrode material under different calcination conditions, it became evident that the material exhibited optimal electrochemical performance when subjected to a temperature of 700 °C for 2 h.

Fe single atoms encapsulated in N, P-codoped carbon nanosheets with enhanced peroxidase-like activity for colorimetric detection of methimazole.

Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop rapid, low cost and accurate colorimetric method with peroxidase-like nanozymes for determination of MMI in medical, nutrition and pharmaceutical studies. Herein, Fe single atoms were facilely encapsulated into N, P-codoped carbon nanosheets (Fe SAs/NP-CSs) by a simple pyrolysis strategy, as certified by a series of characterizations. UV-vis absorption spectroscopy was employed to illustrate the high peroxidase-mimicking activity of the resultant Fe SAs/NP-CSs nanozyme through the typical catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) oxidation. The catalytic mechanism was scrutionously investigated by the fluorescence spectroscopy and electron paramagnetic resonance (EPR) tests. Additionally, the introduced MMI had the ability to reduce the oxidation of TMB (termed oxTMB) as a peroxidase inhibitor, coupled by fading the blue color. By virtue of the above findings, a visual colorimetric sensor was established for dual detection of methimazole (MMI) with a linear scope of 5-50 mM and a LOD of 1.57 mM, coupled by assay of H2O2 at a linear range of 3-50 mM. According to the irreversible oxidation of the drug, its screening with acceptable results was achieved on the sensing platform even in commercial tablets The Fe SAs/NP-CSs nanozyme holds great potential for clinical diagnosis and drug analysis.

Nano-selenium repaired the damage caused by fungicides on strawberry flavor quality and antioxidant capacity by regulating ABA biosynthesis and ripening-related transcription factors.

Recently, studies have shown that pesticides may have adverse effects on the flavor quality of the fruits, but there is still a lack of appropriate methods to repair the damage. This study investigated the effects and mechanism of applying the emerging material, nano­selenium, and two fungicides (Boscalid and Pydiflumetofen) alone or together on the flavor quality and antioxidant capacity of strawberries. The results showed that the two fungicides had a negative impact on strawberry color, flavor, antioxidant capacity and different enzymatic systems. The color damage was mainly attributed to the impact on anthocyanin content. Nano­selenium alleviated the quality losses by increasing sugar-acid ratio, volatiles, anthocyanin levels, enzyme activities and DPPH scavenging ability and reducing ROS levels. Results also showed that these damage and repair processes were related to the regulation of flavor and ripening related transcription factors (including FaRIF, FaSnRK1, FaMYB10, FaMYB1, FaSnRK2.6 and FaABI1), the upregulation of genes on sugar-acid, volatile, and anthocyanin synthesis pathways, as well as the increase of sucrose and ABA signaling molecules. In addition, the application of nano-Se supplemented the selenium content in fruits, and was harmless to human health. This information is crucial for revealing the mechanisms of flavor damage caused by pesticides to strawberry and the repaired of nano­selenium, and broadens the researching and applying of nano­selenium in repairing the damage caused by pesticides.

MSWIFA and cement cooperate in the disposal of soft soil - experimental study on silty sand and silty clay.

Municipal solid waste incineration fly ash (MSWIFA) can be reused as a positive additive to strengthen soft soil. In this study, MSWIFA was initially used as a supplementary solidification material in combination with ordinary Portland cement to prepare fly ash cement-stabilized soil (FACS) with silty sand and silty clay, respectively. The ratio of MWSIFA to total mass was 5%, 10%, and 15%, and the cement content was set as 10% and 15%. The mechanical properties of FACS were evaluated by unconfined compressive strength test. The heavy metal-leaching test was conducted to estimate the environmental risk of FACS. The scanning electron microscope was used to test the micro-structure of FACS. The X-ray diffraction was performed to analyze material composition of FACS. The result indicates that the collaborative solidification of soft soil with MSWIFA and cement is feasible. Regarding the silty clay, the FA had positive effects on the silty clay in the service age (between 50 and 100% with 15% MSWIFA), as the MSWIFA reformulated the initial silty clay structure, resulting in interconnection and pore fill between particles. It can be founded that C-S-H and ettringite are the main products of MSWIFA and cement hydration, which are formed by the hydration of C3S and C2S. Regarding the silty sand, the MSWIFA decreased the peak strength (between 35 and 48% with 15% MSWIFA) but increased the ductility of the stabilized cement. Under the same mix proportions, the leaching toxicities of Zn and Pb in FACS of silty clay were obviously lower than were those of silty sand. Generally, the leaching concentrations of tested metals under all the mix proportions were well below the limit value set by GB 18598-2019 for hazardous waste landfill. Thus, the reuse of MSWIFA in cement-stabilized soil would be one of the effective methods in soft soil treatment and solid waste reduction.

Fusobacterium nucleatum exacerbates the progression of pulpitis by regulating the STING-dependent pathway.

Bacterial infection is the main cause of pulpitis. However, whether a dominant bacteria can promote the progression of pulpitis and its underlying mechanism remains unclear. We provided a comprehensive assessment of the microbiota alteration in pulpitis using 16S rRNA sequencing. Fusobacterium nucleatum was the most enriched in pulpitis and played a pathogenic role accelerating pulpitis progression in rat pulpitis model. After odontoblast-like cells cocultured with F. nucleatum, the stimulator of interferon genes (STING) pathway and autophagy were activation. There was a float of STING expression during F. nucleatum stimulation. STING was degraded by autophagy at the early stage. At the late stage, F. nucleatum stimulated mitochondrial Reactive Oxygen Species (ROS) production, mitochondrial dysfunction and then mtDNA escape into cytosol. mtDNA, which escaped into cytosol, caused more cytosolic mtDNA binds to cyclic GMP-AMP synthase (cGAS). The release of IFN-ß was dramatically reduced when mtDNA-cGAS-STING pathway inhibited. STING-/- mice showed milder periapical bone loss and lower serum IFN-ß levels compared with wildtype mice after 28 days F. nucleatum-infected pulpitis model establishment. Our data demonstrated that F. nucleatum exacerbated the progression of pulpitis, which was mediated by the STING-dependent pathway.

Lack of incremental value of three-dimensional measurement in assessing invasiveness for lung cancer.

OBJECTIVES: The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma. METHODS: A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features. Clinicopathological characteristics and radiomic signatures were identified in both cohorts. CTR and radiomic score for every patient were calculated. The performance of CTR and radiomic models were tested and validated in the respective cohorts. RESULTS: A total of 818 patients from Guangdong Provincial People's Hospital were included in the primary cohort, while 474 patients from Shenzhen People's Hospital constituted an independent validation cohort. Both CTR and radiomic score were identified as independent factors for predicting pathological invasiveness. CTR in two- and three-dimensional modalities exhibited comparable results with areas under the receiver operating characteristic curves and were demonstrated in the validation cohort (area under the curve: 0.807 vs 0.826, P = 0.059) Furthermore, both CTR in two- and three-dimensional modalities was able to stratify patients with significant relapse-free survival (P < 0.000 vs P < 0.000) and overall survival (P = 0.003 vs P = 0.001). The radiomic models in two- and three-dimensional modalities demonstrated favourable discrimination and calibration in independent cohorts (P = 0.189). CONCLUSIONS: Three-dimensional measurement provides no additional clinical benefit compared to two-dimensional.

Newcastle Disease Virus (NDV)-based vaccine candidate against SARS-CoV-2 Omicron by intranasal immunization.

Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Currently, the development of affordable vaccine against Omicron variant of concern (VOC) is necessary. Here, we assessed the safety and immunogenicity of a SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing the spike (S) protein of Omicron BA.1 administrated intranasally (IN) or intramuscularly (IM) in Golden Syrian hamster model. Immunogenicity studies showed that the prime-boost regimen elicited high antibody titers and the modified S antigen (Sm-F) could induce robust antibody response in low dosage immunization through IN route. Sera of the immunized hamsters provided effective cross-neutralizing activity against different Omicron variants, the prototype and delta strains of SARS-CoV-2. Moreover, the vaccine could provide complete immunoprotection in hamsters against the Omicron BA.1 challenge by either intranasal or intramuscular immunization. Overall, our study provides an alternative nasal vaccine against the SARS-CoV-2 Omicron variants.

Fe-Ni dual-single atoms nanozyme with high peroxidase-like activity for sensitive colorimetric and fluorometric dual-mode detection of cholesterol.

Cholesterol is widely existed in nerve myelin sheath and various membrane structures, whose abnormal level would deteriorate human cells or even cause diseases. Herein, Fe-Ni dual-single-atom nanozyme was efficiently incorporated into N-doped carbon nanosheets (FeNi DSAs/N-CSs) by a simple calcination method. Its nanozyme activity and catalytic mechanism were investigated in details. The FeNi DSAs/N-CSs nanozyme showed superior peroxidase-like property, which was applied for the dual-mode determination of hydrogen peroxide (H2O2) and cholesterol. The colorimetric/fluorometric assays of H2O2 displayed the linear ranges of 1-50 mM and 5-40 mM with low limits of detection of 0.45 mM and 3.33 mM, respectively. In parallel, there exhibited the linear ranges of 0.5-5.0 mM and 0.25-5.0 mM for the colorimetric/fluorometric analysis of cholesterol, coupled with the limits of detection down to 0.19 mM and 0.044 mM, respectively. This work provided a rapid, cost-effectiveness and simple colorimetric/fluorometric method for sensitive dual-mode detection of cholesterol in human serum samples.

Case report: Novel DGUOK variants associated with idiopathic non-cirrhotic portal hypertension in a Han Chinese child.

DGUOK deficiency has primarily been associated with lethal hepatic failure with or without hypotonia, nystagmus, and psychomotor retardation, features typical of mitochondrial disease. A study in 3 Turkish children identified homozygosity for a variant in DGUOK as associated with idiopathic non-cirrhotic portal hypertension (INCPH). However, no further instances of INCPH associated with DGUOK variants have been reported. We here describe a fourth patient with DGUOK variants and childhood-onset INCPH, a 12-year-old Han Chinese boy, reporting clinical manifestations, histopathologic findings, and results of genetic studies. The child presented with hepatosplenomegaly; portal hypertension and hypersplenism were found. Vascular changes with hepatic fibrosis (Scheuer score 3) were observed on liver biopsy. Whole-exome sequencing and family analyses revealed compound heterozygosity for the DGUOK (NM_080916.3) variants c.778_781dup, (p.Thr261Serfs*28) and c.831_832del, (p.*278Thrfs*9) in the proband. These observations support ascription of instances of INCPH in children to variation in DGUOK.

Incidence, risk factors, and outcomes of recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Focal segmental glomerulosclerosis is the most prevalent acquired kidney disease leading to end-stage renal disease in children and has a propensity for recurring in the transplanted kidney. The recurrence of FSGS after kidney transplantation in children varies greatly. In addition, the risk factors and outcomes of recurrence of FSGS remain controversial. This study evaluated the recurrence rate, risk factors, and prognosis of FSGS after kidney transplantation in order to provide advice and assistance in clinical decision-making for pediatric kidney transplantation. METHODS: PubMed, Embase, Web of Science, CNKI, and other databases were searched from the establishment of the repository to March 2022. We extracted data on incidence, risk factors, and outcomes. RESULTS: The results showed that the recurrence rate of primary FSGS in children after renal transplantation was 48% (95% CI 36%-59%) and the recurrence rate of FSGS (all forms) was 35% (95% CI 17%-52%). The graft loss rate of primary FSGS in children after kidney transplantation was 29% (95% CI 17%-42%) and the graft loss rate of FSGS (all forms) was 29% (95% CI 4%-62%). 57% (95% CI 42%-73%) of pediatric patients with recurrent primary FSGS showed complete remission. Risk factor analyses showed that age of onset (SMD .69, 95% CI .20-1.19, p = .006) was related to the recurrence of primary FSGS, whereas the living related donor was not a risk factor for recurrent primary FSGS in pediatrics after kidney transplantation (OR 1.22, 95% CI .48-3.10, p = .674). CONCLUSIONS: The recurrence rate and graft loss rate of FSGS in children after kidney transplantation were relatively high. Age at onset was associated with a risk for recurrent primary FSGS, whereas the living related donor was not a risk factor for recurrent FSGS in pediatric kidney recipients.

[Effects of Different Control Measures on Cadmium and Lead Accumulation and Quality in Lettuce].

To explore the safe utilization technology of farmland polluted by the heavy metals cadmium (Cd) and lead (Pb) and to realize the safe production of agricultural products, a pot experiment was conducted to investigate the effects of two soil passivators and five foliar inhibitors on Cd and Cd-accumulation and quality of lettuce with low Pb and Cd accumulation (KCW). The results showed that different control measures had different effects on the soil pH value of lettuce, and the application of 45 g·m-2biochar-based passivator had the most significant difference in improving the soil pH value, which was increased by 0.8 units compared with that in CK. By using 72 g·m-2 of humic acid passivator yielded notable difference in reducing the soil pH value of lettuce. A reduction of 0.25 units was achieved compared with that in CK. Among all the control measures, the application of 45 g·m-2 biocharcoal-based passivation agent had the best effect on reducing soil available Cd content, which was significantly reduced by 53% compared with that in CK, and the application of 135 g·m-2biocharcoal-based passivation agent had the best effect on reducing soil available Pb content, which was significantly reduced by 64% compared with that in CK. Spraying 0.8% FAK-Zn foliar inhibitor not only had the best control effect on reducing Cd and Pb contents in the edible parts of lettuce, which were significantly reduced by 77% and 60%, respectively, compared with that in CK, but it also significantly reduced Cd and Pb enrichment coefficients and transport coefficients from the root to the edible parts of the lettuce. Different control measures had different effects on the nutritional quality of lettuce, and 0.4% FAK-Zn foliar inhibitor had the best effect on soluble protein. The 0.6% FAK-Zn had the best effect on soluble sugar, and the 0.4% FAK-Zn inhibitor had the best effect on vitamin C content. The application of biocarbon-based passivator could effectively repair lettuce soil polluted by Cd and Pb, whereas the application of FAK-Zn leaf surface inhibitor could effectively inhibit the accumulation, absorption, and transfer of Cd and Pb in lettuce; improve the nutritional quality of lettuce; provide a theoretical basis for safe production of vegetables polluted by heavy metals; and promote the recycling of resources and environment.

Identifying the active ingredients of carbonized Typhae Pollen by spectrum-effect relationship combined with MBPLS, PLS, and SVM algorithms.

Typhae Pollen (TP) and its carbonized product (carbonized Typhae Pollen, CTP), as cut-and-dried herbal drugs, have been widely used in the form of slices in clinical settings. However, the two drugs exhibit a great difference in terms of their clinical efficacy, for TP boasts an effect of removing blood stasis and promoting blood circulation, while CTP typically presents a hemostatic function. Since the active ingredients of CTP, so far, still remain unclear, this study aimed at identifying the active ingredients of CTP by spectrum-effect relationship approach coupled with multi-block partial least squares (MBPLS), partial least squares (PLS), and support vector machine (SVM) algorithms. In this study, the chemical profiles of a series of CTP samples which were stir-fried for different duration (denoted as CTP0∼CTP9) were firstly characterized by UHPLC-QE-Orbitrap MS. Then the hemostatic effect of the CTP samples was evaluated from the perspective of multiple parameters-APTT, PT, TT, FIB, TXB2, 6-keto-PGF1α, PAI-1 and t-PA-using established rat models with functional uterine bleeding. Subsequently, MBPLS, PLS and SVM were combined to perform spectrum-effect relationship analysis to identify the active ingredients of CTP, followed by an in vitro hemostatic bioactivity test for verification. As a result, a total of 77 chemical ingredients were preliminarily identified from the CTP samples, and the variations occurred in these ingredients were also analyzed during the carbonizing process. The study revealed that all the CTP samples, to a varying degree, showed a hemostatic effect, among which CTP6 and CTP7 were superior to the others in terms of the hemostatic effect. The block importance in the projection (BIP) indexes of MBPLS model indicated that flavonoids and organic acids made more contributions to the hemostatic effect of CTP in comparison to other ingredients. Consequently, 9 bioactive ingredients, including quercetin-3-O-glucoside, kaempferol-3-O-rutinoside, quercetin, kaempferol, isorhamnetin, 2-methylenebutanedioic acid, pentanedioic acid, benzoic acid and 3-hydroxybenzoic acid, were further identified as the potential active ingredients based on PLS and SVM models as well as the in vitro verification. This study successfully revealed the bioactive ingredients of CTP associated with its hemostatic effect, and also provided a scientific basis for further understanding the mechanism of TP processing. In addition, it proposed a novel path to identify the active ingredients for Chinese herbal medicines.

[Research advances in pharmacotherapy for rare diseases in children]. / å„¿ç«¥ç½•è§ç— è¯ç‰©æ²»ç–—æ–°è¿›å±•.

There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.

[Simulation of Pollution Apportionment and Optimization of Control Methods in Watershed Scale: A Case Study of the Shun'an Watershed in Tongling City].

The protection of the Yangtze River is an important national strategy in China, but it faces many problems such as difficult water environment protection, unclear pollution sources, and low integration of measures. Aimed at addressing watershed scale multi-source pollution together with facing the bottleneck method, by combining research data analysis, mechanism model, and intelligent algorithm optimization, this study built the framework for accurate pollution apportionment, measures evaluation, and overall measure optimization. Shun'an watershed in Tongling City of Anhui Province was set as an example for the application. The results showed that the new method could accurately quantify the impacts of planting industry, rural life, livestock and poultry breeding, aquaculture, industrial sewage, and domestic sewage in the watershed and evaluate the overall effects of various measures. The multi-objective optimization algorithm provided a cooperative multi-source pollution control scheme with higher cost performance and better environmental benefit by comparing the cost effectiveness of various schemes systematically. The optimization scheme showed that total nitrogen could be reduced by 1274.24 t·a-1 in wet years, 855.24 t·a-1 in normal years, and 381.96 t·a-1 in dry years. Total phosphorus was reduced by 321.42 t·a-1 in wet years, 159.80 t·a-1 in normal years, and 42.93 t·a-1 in dry years, such that the water quality reached the surface class Ⅲ water quality standard. These research results can be extended to other watersheds and provide a method reference for water environment protection under the background of the high-quality development of watersheds.