The problem of pediatric drugs has been the challenges facing the world. The two most important issues are the lack of appropriate drug dosage forms for children and the safety and effectiveness data of drug use in children. How to encourage production enterprises to produce drug varieties, specifications and dosage forms suitable for children use, guide drug manufacturers to obtain drug use data are the most important work for pediatric drugs.Based on the literature home and abroad, we analyze the regulatory policies for the research and development(RD) and application of pediatric drugs in the USA, EU and Japan, which have made great efforts to encourage enterprises to conduct pediatric research. Their successful experiences are summarized and can be used as reference for the establishment of the policies adaptive to the situation of China for the RD of pediatric drugs.

Objective To investigate the prevalence of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among local residents in Yantai City, Shandong Province in 2021, so as to provide insights into formulation of anisakiasis control interventions. Methods Marine fishes were purchased from Shunxin Port, Yantai City, Shandong Province in November 2021, and the presence of Anisakis was detected in different species of fishes and different fish sites. The correlations between body length and weight of marine fish and intensity of Anisakis infections were examined using Spearman’s rank correlation analysis, and the dietary habits and anisakiasis control knowledge were investigated using questionnaire surveys among local residents. Results A total of 201 marine fishes belonging to 20 species were dissected, and Anisakis was detected in 77 marine fishes (38.31%) belonging to 11 species (55.00%), with a mean infection intensity of 45.04 parasites per fish (3 468/77). Spearman’s rank correlation analysis revealed that the body length (r_s = 0.74, P < 0.05) and weight (r_s = 0.79, P < 0.01) of the monkfish correlated positively with the intensity of Anisakis infections, and the body length (r_s = 0.68, P < 0.05) of the flatfish correlated positively with the intensity of Anisakis infections, while no correlations were examined between the body length or weight of other marine fishes and the intensity of Anisakis infections. Of all respondents, 53.38% men and 56.67% women did not know anisakiasis control knowledge at all, and there was a significant difference in the proportion of respondents using separate chopping boards for raw and cooked food from different villages (χ² = 17.89, P < 0.01), while there was an age-specific proportion of respondents with habitats of eating raw or semi-raw seafood (χ² = 28.27, P < 0.01). Conclusions The prevalence and intensity of Anisakis infections were high in coastal marine fishes in Yantai City in 2021, and the awareness of anisakiasis control knowledge was low among local residents. Intensified health education pertaining to anisakiasis control knowledge is recommended to reduce the risk of Anisakis infections.

OBJECTIVE: To investigate the role of high mobility group protein 1(HMGB1) in toluene diisocyanate(TDI) induced nucleotide-binding oligomerization domain like receptor family pyrin domain-containing 3(NLRP3) inflammasome activation in human bronchial epithelial cells(HBECs). METHODS: i) The TDI-human serum albumin(HSA) stimulation experiment: the HBECs in logarithmic growth phase were randomly divided into control group, low-, medium-and high-dose groups that were pretreated with TDI-HSA with the final concentration of 0.00, 40.00, 80.00 and 120.00 mg/L for 12 hours. ii) The HMGB1 expression inhibition experiment: the HBECs in logarithmic growth phase were divided into control group, TDI-HSA group, TDI-HAS+negative-siRNA group, and TDI-HAS+HMGB1-siRNA group. The cells in TDI-HAS+negative-siRNA group and TDI-HAS+HMGB1-siRNA group were infected with HBECs with negative-siRNA lentivirus and HMGB1-siRNA lentivirus, respectively. Cells in these two groups and the TDI-HSA group were treated with 120.00 mg/L of TDI-HSA for 12 hours. The cells in the control group were not treated with TDI-HAS. iii) The expression of HMGB1, NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), pro-caspase-1 and caspase-1 p20 proteins in all groups were detected by Western blot. The number of NLRP3 and caspase-1 inflammasome in TDI-HSA stimulation experiment was observed by immunofluorescence method. RESULTS: i) TDI-HSA stimulation experiment: the relative protein expression of HMGB1 and ASC was higher in HBECs of medium-and high-dose groups than that of control group(all P values were <0.01). The relative protein expression of NLRP3 and casepase-1 p20 and the number of NLRP3-caspase-1 inflammasome were higher in HBECs of 3 dose groups than that of control group(all P values were <0.01). The number of NLRP3-caspase-1 inflammasome in HBECs increased obviously in low-, medium-and high-dose groups as compared to the control group(all P values were <0.05). The number of NLRP3-caspase-1 inflammasome in HBECs increased with the increase of TDI-HSA dose(all P values were <0.01). ii) The HMGB1 expression inhibition experiment: the relative protein expression of HMGB1, NLRP3, ASC, pro caspase-1 and caspase-1 p20 in HBECs were higher in the TDI-HSA group and TDI-HSA + negative-siRNA group than those of the control group(all P values were <0.01). The above indexes of HBECs were lower in the TDI-HAS + HMGB1-siRNA group than those in the TDI-HSA group and TDI-HSA + negative-siRNA group(all P values were <0.01).CONCLUSION: TDI treatment in HBECS can induce the increase of HMGB1 protein expression and activate NLPR3 inflammasome. Inhibition of HMGB1 expression can down-regulate the expression of NLPR3 and its related proteins.

OBJECTIVE: To explore the therapeutic effect of tetrandrine(TET) on silicosis model rats and its toxic effect on liver and kidney function. METHODS: The specific pathogen free healthy male Wistar rats were randomly divided into the control group, the model group and the TET group, with 14 rats in each group. By un-exposure tracheal injection method, the rats in the model and TET groups were given one-time tracheal infusion of free silicon dioxide suspension with a mass concentration of 50 g/L to establish the rat model of silicosis. Rats in the control group were infused with 1 mL of 0.9% sodium chloride solution with the same method. On the second day after the model was established, the TET group was given 30 mg/kg body mass of TET solution by gavage. The other two groups were given the same amount of 0.9% sodium chloride solution. The treatment was once per day, six times per week. Seven rats in each group were sacrificed on the 28 th and 56 th days after modeling. The morphological change of the lung, liver and kidney tissues of each group was observed. The enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1), interleukin(IL)-1β and IL-6, in the lung tissues of rats in each group. The activities of aminotransferase(ALT), aspartate aminotransferase(AST) and the levels blood urea nitrogen(BUN), creatinine(CRE) were detected by automatic biochemical analyzer. RESULTS: The lung organ coefficients of rats in the TET group were lower than those of the model group on the 28 th and 56 th days(all P<0.05). The lung organ coefficient of the rats in the TET group on the 56 th day was higher than that in the same group on the 28 th day(P<0.05). The lung tissue structure of the control group was normal. After modeling, the lung tissues of rats in model group showed different degrees of pathological changes such as alveolar structure destruction, inflammatory cell infiltration, and fibrosis on the 28 th and 56 th days. The degree of pathological changes in TET group was less than that of the model group. In the lung tissues of rats in the model group, the levels of TNF-α, TGF-β1, IL-1β and IL-6 were higher than those of the control group(all P<0.01). The levels of TNF-α, TGF-β1, IL-1β and IL-6 in the lung tissues of rats in the TET group were lower than that of the model group(all P<0.01), but there was no statistically significant difference when compared with the control group(all P>0.05). The activities of ALT and AST in the TET group were higher than those in the model group and the control group(all P<0.01). The level of serum BUN in TET group was higher than that in control group(P<0.01), but it showed no statistical difference when compared with the control group(P>0.05). The level of serum CRE in each group showed no significant difference(P>0.05). There were no abnormal pathological changes found in the liver and kidney tissues of rats in each group at different times. CONCLUSION: TET can reduce the inflammatory response in silicosis rats and improve lung tissue fibrosis; however, the therapeutic dose may have certain toxicity to the liver and kidney of the silicosis rats.

BACKGROUNDThe E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) negatively regulates phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor development and chemosensitivity of lung adenocarcinoma (ADC).

METHODSWe retrospectively investigated the expression and significance of NEDD4-1, PTEN, and p-Akt proteins in 135 paired ADC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthermore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- (4,5-dimethylthiazol-2-yl) -5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)- 2H-tetrazolium method. The ability of migration and invasion of A549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase (PI3K)/Akt activity, and its downstream target proteins.

RESULTSNEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression of NEDD4-1 in ADC (78.5%, 106/135) was significantly much higher than that in adjacent normal lung tissue (13.3%, 29/135, P < 0.01), and it was associated with lymph node metastasis, tumor-node-metastasis (TNM) stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC (60.7% vs. 100.0% in noncancerous specimens, P = 0.007), and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues (71.1% 96/135) was much higher than that in adjacent lung epithelial cells (6.7%, 9/135, P < 0.01). Kaplan-Meier and multivariate analysis demonstrated that expressions of NEDD4-1 and PTEN were both independent risk factors for survival in patients with lung ADC. NEDD4-1 knockdown in vivo decreased proliferation, migration, and invasion and improved chemosensitivity to cisplatin and paclitaxel in A549 cells. NEDD4-1 knockdown also significantly enhanced PTEN expression and inhibited p-Akt activity and downstream target proteins.

CONCLUSIONSNEDD4-1 upregulation may contribute to the progression of lung ADC. NEDD4-1 may regulate the proliferation, invasion, migration, and chemoresistance of lung ADC cells through the PI3K/Akt pathway, suggesting that it may be regarded as a therapeutic target for the treatment of lung ADC.

Objective: To study the efficacy network and potential mechanisms of effects of Chaihu Longgu Muli Decoction in the treatment of essential hypertension by using network pharmacology methods. Methods: TCMSP, TCMID, and Stitch were used to obtain the components and their corresponding targets. PubMed, CTD, TTD, OMIM, and DrugBank were used to search disease targets of essential hypertension. The common targets between components and disease targets were screened and builded the “compound - target” efficacy network and the protein-protein interaction network by STRING and Cytoscape. The key components and core targets of Chaihu Longgu Muli Decoction in the treatment of hypertension were screened in these networks. Finally, relevant software was applied to GO analysis and pathway analysis of core targets to predict potential mechanisms. Results: A total of 137 components of Chaihu Longgu Muli Decoction and 168 targets of essential hypertension were screened. According to the analysis, quercetin, β-sitosterol, kaempferol, and stigmasterol were found as the four key components and 12 core targets such as IL-6, AKT1, and MAPK8 were found involving the Chaihu Longgu Muli Decoction-induced treatment of essential hypertension. The result of GO analysis and KEGG pathway analysis showed that the mechanisms of Chaihu Longgu Muli Decoction for treating essential hypertension were related to pathways such as activation of AP-1 family transcription factors, interleukin-10 signaling, interleukin-4 signaling, interleukin-13 signaling, the intrinsic pathway of apoptosis, and MAPK targeting/by MAP kinase-mediated nuclear events. Conclusion: The mechanisms of the effect of Chaihu Longgu Muli Decoction in the treatment of essential hypertension were through the above-mentioned “multi-components-multi-targets-multi-pathways”. This study provides a foundation for further investigation of the effective compound and specific mechanisms of Chaihu Longgu Muli Decoction in the treatment of essential hypertension.

Primary pulmonary synovial sarcoma is a rare pulmonary malignant tumor originated from primitive mesenchymal, which has short overall survival and poor prognosis. Related case reports are lacked at home and abroad. In recent years, the development of targeted therapy has brought remarkable benefits to cancer patients. Apatinib (Hengrui Pharmaceutical Co. Ltd, Jiangsu, People's Republic of China) is a small molecule vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, which selectively inhibits VEGFR-2 and blocks the VEGF signal pathway, then strongly inhibiting the tumor angiogenesis. Apatinib has shown favorable therapeutic effect and acceptable toxicity on various tumors. Here we report a case of primary pulmonary synovial sarcoma with postoperative multiple metastases treated with apatinib, in order to provide a new considerable treatment.
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Humans ; Lung Neoplasms ; drug therapy ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Metastasis ; Postoperative Period ; Pyridines ; therapeutic use ; Sarcoma, Synovial ; drug therapy ; pathology ; surgery

Angiography ; Cardiac Catheterization ; Child ; Child, Preschool ; Female ; Heart Septal Defects, Ventricular ; diagnosis ; surgery ; Humans ; Male ; Septal Occluder Device ; Treatment Outcome

OBJECTIVEThis study was aimed to investigate the risk factors of renal impairment and the predictive factors of renal function recovery so as to provide basis for its prevention and treatment.

METHODSMedical records of 161 patients with MM firstly diagnosed from January 2007 to April 2013 were analyzed retrospectively. Among them 58 cases accompanied with renal insufficiency (group A, others belong to group B) and 39 of them regain normal renal function after some treatment. The possible related renal impairment risk factors and reversible predictors were analyzed with chi-square test for significance firstly, then factors that have significant difference were entered into multivariate logistic regression analysis.

RESULTSSystolic blood pressure (SBP), hemoglobin, uric acid, blood calcium, phosphorus, serum β2-microglobulin, urine β2-microglobulin levels, M-component type, light chain type, nephrotoxic drug use, infection in group A had significant difference (P<0.05) compared with those in group B; the systolic blood pressure, diastolic blood pressure, platelet, globulin, blood calcium, and urine β2-microglobulin levels, the chemotherapy applied and the response to chemotherapy in reversed group were significantly different from no-reversed group (P<0.05). Multivariate logistic regression showed that light chain type, Hb, uric acid, Ca were the independent risk factors for the development of renal failure in MM, and Ca, chemotherapy and the response to chemotherapy were the predictors of renal function recovery.

CONCLUSIONHigh blood calcium, severe anemia, λ light chain, high uric acid are the independent risk factors of renal impairment in MM patients. Patients with high blood calcium before treatment easily regain normal renal function after effective chemotherapy. Bortezomib-based chemotherapy has higher response rate and higher reversal rate, and it may be related with its unique mechanism.

Bortezomib ; Humans ; Kidney ; Logistic Models ; Multiple Myeloma ; Renal Insufficiency ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the relationship between semi-quantification of urine paraquat and the severity of acute paraquat poisoning, and to evaluate the prognostic value of the test in patients with acute paraquat poisoning.

METHODSA total of 179 patients with acute paraquat poisoning were categorized into four groups according to their semi-quantification results of urine paraquat: +group (n = 36), ++group (n = 23), +++ group (n = 25), and ++++group (n = 95). The clinical features, severity of hepatic and renal injuries, respiratory failure, and clinical classification were compared between these four groups. Kaplan-Meier analysis was used to evaluate the survival rate.

RESULTSThe 60-day mortality was 45.25% (81/179). The amount of ingestion increased significantly from +group to ++++group (P < 0.05). No patient in +group was found to have serious complications, while most patients in ++++group suffered organ dysfunction or even organ failure. The incidence of acute respiratory failure, renal failure, and hepatic failure in ++++group was significantly higher than that in +group, ++group, and +++group (P < 0.05). The urine paraquat concentration was positively correlated with the clinical severity of acute paraquat poisoning (Spearman correlation coefficient = 0.720, P < 0.01). Kaplan-Meier survival analysis showed that the mortality of ++++group (73.7%) was significantly higher than that of +++group (40%), ++group (4.3%), and +group (0%) (P < 0.05).

CONCLUSIONThe semi-quantification of urine paraquat is a promising test in evaluating the severity of acute paraquat poisoning. This test can be used to guide therapy and to predict the outcomes of patients suffering acute paraquat poisoning.

Acute Disease ; Adolescent ; Adult ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Paraquat ; poisoning ; urine ; Prognosis ; Young Adult