A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer.

BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.

Expansion of YALIcloneHR toolkit for Yarrowia lipolytica combined with Golden Gate and CRISPR technology.

Metabolic Engineering of yeast is a critical approach to improving the production capacity of cell factories. To obtain genetically stable recombinant strains, the exogenous DNA is preferred to be integrated into the genome. Previously, we developed a Golden Gate toolkit YALIcloneNHEJ, which could be used as an efficient modular cloning toolkit for the random integration of multigene pathways through the innate non-homologous end-joining repair mechanisms of Yarrowia lipolytica. We expanded the toolkit by designing additional building blocks of homologous arms and using CRISPR technology. The reconstructed toolkit was thus entitled YALIcloneHR and designed for gene-specific knockout and integration. To verify the effectiveness of the system, the gene PEX10 was selected as the target for the knockout. This system was subsequently applied for the arachidonic acid production, and the reconstructed strain can accumulate 4.8% of arachidonic acid. The toolkit will expand gene editing technology in Y. lipolytica, which would help produce other chemicals derived from acetyl-CoA in the future.

De novo transcriptome sequencing of Impatiens uliginosa and the analysis of candidate genes related to spur development.

BACKGROUND: Spur, a structure capable of producing and storing nectar, not only plays a vital role in the pollination process but also promotes the rapid diversification of some plant lineages, which is considered a key innovation in plants. Spur is the focus of many studies, such as evolution and ecological hypothesis, but the current understanding of spur development is limited. High-throughput sequencing of Impatiens uliginosa was carried out to study the molecular mechanism of its spur development, which is believed to provide some insights into the spur development of Impatiens. RESULTS: Transcriptomic sequencing and analysis were performed on spurs and limbs of I. uliginosa at three developmental stages. A total of 47.83 Gb of clean data were obtained, and 49,716 unigene genes were assembled. After comparison with NR, Swiss-Prot, Pfam, COG, GO and KEGG databases, a total of 27,686 genes were annotated successfully. Through comparative analysis, 19,356 differentially expressed genes were found and enriched into 208 GO terms and 146 KEGG pathways, among which plant hormone signal transduction was the most significantly enriched pathway. One thousand thirty-two transcription factors were identified, which belonged to 33 TF families such as MYB, bHLH and TCP. Twenty candidate genes that may be involved in spur development were screened and verified by qPCR, such as SBP, IAA and ABP. CONCLUSIONS: Transcriptome data of different developmental stages of spurs were obtained, and a series of candidate genes related to spur development were identified. The importance of genes related to cell cycle, cell division, cell elongation and hormones in spur development was clarified. This study provided valuable information and resources for understanding the molecular mechanism of spur development in Impatiens.

Exosomal encapsulation of miR-125a-5p inhibited trophoblast cell migration and proliferation by regulating the expression of VEGFA in preeclampsia.

This study is aimed to examine the association between umbilical cord blood (UCB) derived exosomal microRNA (miRNA) with preeclampsia (PE) and to further explore the mechanism of a key differential gene (hsa-miR-125a-5p) in preeclampsia. Umbilical cord blood exosomal miRNA(exo-miRNA) from normal pregnant women and pregnant women with preeclampsia was processed via miRNA sequencing. Quantitative real-time polymerase chain reaction (QRT-PCR) was performed to assess the expression of miR-125a-5p in normal and PE placental tissues and peripheral blood derived exosomes in the third trimester. Human trophoblast cell line HTR8/SVneo was assigned as the negative control and miR-125a-5p mimics. QRT-PCR and Western blot were performed to identify the expressions of miR-125a-5p and vascular endothelial growth factor A (VEGFA). CCK8, flow cytometry, wound-healing and Transwell assays were used to analyze the effect of miR-125a-5p on HTR8/SVneo cell migration, proliferation, and cycle distribution. Tube formation was performed to estimate the angiogenesis ability of miR-125a-5p on HUVECs. In conclusion, miR-125a-5p expression in PE placental tissues was higher than in normal subjects, while the expression of VEGFA was lower in PE placental tissues. We then compared the miR-125a-5p mimics group with the negative control group and found that in the mimics group, the cell migration, proliferation and angiogenesis abilities were decreased, and more cells were arrested in the S stage. Our study systematically profiled the UCB exo-miRNA in normal and PE pregnant women and demonstrated that dysregulation of miR-125a-5p might affect HTR8/SVneo cell proliferation and migration and inhibit angiogenesis by regulating VEGFA, indicating that miR-125a-5p is involved in the progression of PE.

Effects of oral treatments on clinical outcomes in pulmonary arterial hypertension: A systematic review and meta-analysis.

BACKGROUND: Many targeted therapies have been approved for pulmonary arterial hypertension (PAH), most of which are in oral forms. However, the effects of these drugs on lifesaving are unclear. Our objective was to evaluate the effects of oral treatments on clinical outcomes especially all-cause mortality in patients with PAH. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for relevant articles up to April 2014. Randomized, double-blind, parallel-group clinical trials that compared oral agents with placebo were selected. Data for populations, interventions, and outcomes were extracted independently by 2 investigators, and disagreements were resolved by consensus. Quality assessment was performed using the Cochrane risk-of-bias tool. RESULTS: Twenty-one randomized, controlled, clinical trials involving 5105 patients were identified in the primary analysis. The overall estimated odds ratio (OR) of combined clinical worsening (CCW) events between active treatment groups and control groups was 0.55 (95% CI 0.47-0.64, P < .001). However, the effect of oral treatments on reducing all-cause mortality was not statistically significant (OR 0.82, 95% CI 0.61-1.10, P = .192), which was consistent for approved drugs (OR 0.84, 95% CI 0.61-1.18, P = .316) and drugs that were not approved (OR 0.72, 95% CI 0.36-1.44, P = .352). In the sensitivity analysis, a significant reduction was achieved in CCW events (P < .001) but not in all-cause mortality (P = .057). CONCLUSIONS: This pooled analysis shows the benefits of oral treatments on CCW events in patients with PAH. However, these drugs seem to exhibit less favorable effects on life expectancy in the short-term follow-up, suggesting further evaluation is required.

[Effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension].

OBJECTIVE: To investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension. METHODS: A randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment. RESULTS: After treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05). CONCLUSION: In patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.

Predictive value of lactate dehydrogenase for Mycoplasma pneumoniae necrotizing pneumonia in children based on decision curve analysis and dose-response analysis.

Mycoplasma pneumoniae necrotizing pneumonia (MPNP) has a long and severe disease course, which seriously threatens to jeopardize patients' lives and health. Early prediction is essential for good recovery and prognosis. In the present study, we retrospect 128 children with MPNP and 118 children with Mycoplasma pneumoniae pneumonia combined with pulmonary consolidation to explore the predictive value of lactate dehydrogenase (LDH) in children with MPNP by propensity score matching method, multiple logistic regression analysis, dose-response analysis and decision curve analysis. The WBC count, PLT count and percentage of neutrophils were significantly higher in necrosis group than consolidation group. The serum CRP, PCT, ESR, D-D, FIB, ALT, LDH, IgG and IgM were significantly higher in necrosis group. Compared to consolidation group, necrosis group is more severe in chest pain and dyspnea. Multivariate logistic regression analysis showed that duration of LDH levels, high fever, D-dimer, and fibrinogen were independent predictive factors for the incidence of MPNP. Restricted cubic spline analysis showed that a non-linear dose-response relationship between the continuous changes of LDH level and the incidence of MPNP. Decision curve analysis revealed that LDH had an important clinical value in predicting MPNP. This study provides a potential serologic indicator for early diagnosis of MPNP.

An Unsupervised Error Detection Methodology for Detecting Mislabels in Healthcare Analytics.

Medical datasets may be imbalanced and contain errors due to subjective test results and clinical variability. The poor quality of original data affects classification accuracy and reliability. Hence, detecting abnormal samples in the dataset can help clinicians make better decisions. In this study, we propose an unsupervised error detection method using patterns discovered by the Pattern Discovery and Disentanglement (PDD) model, developed in our earlier work. Applied to the large data, the eICU Collaborative Research Database for sepsis risk assessment, the proposed algorithm can effectively discover statistically significant association patterns, generate an interpretable knowledge base for interpretability, cluster samples in an unsupervised learning manner, and detect abnormal samples from the dataset. As shown in the experimental result, our method outperformed K-Means by 38% on the full dataset and 47% on the reduced dataset for unsupervised clustering. Multiple supervised classifiers improve accuracy by an average of 4% after removing abnormal samples by the proposed error detection approach. Therefore, the proposed algorithm provides a robust and practical solution for unsupervised clustering and error detection in healthcare data.

Chinese expert consensus on diagnosis and management of gastroesophageal reflux disease in the elderly (2023).

Gastroesophageal reflux disease (GERD) in the elderly is characterized by atypical symptoms, relatively severe esophageal injury, and more complications, and when GERD is treated, it is also necessary to fully consider the general health condition of the elderly patients. This consensus summarized the epidemiology, pathogenesis, clinical manifestations, and diagnosis and treatment characteristics of GERD in the elderly, and provided relevant recommendations, providing guidance for medical personnel to correctly understand and standardize the diagnosis and treatment of GERD in the elderly.

The cellular and molecular basis of the spur development in Impatiens uliginosa.

The nectar spur is an important feature of pollination and ecological adaptation in flowering plants, and it is a key innovation to promote species diversity in certain plant lineages. The development mechanism of spurs varies among different plant taxa. As one of the largest angiosperm genera, we have little understanding of the mechanism of spur development in Impatiens. Here, we investigated the initiation and growth process of spurs of Impatiens uliginosa based on histology and hormone levels, and the roles of AUXIN BINDING PROTEIN (ABP) and extensin (EXT) in spur development were explored. Our results indicate that the spur development of I. uliginosa is composed of cell division and anisotropic cell elongation. Imbalances in spur proximal-distal cell division lead to the formation of curved structures. Endogenous hormones, such as auxin and cytokinins, were enriched at different developmental stages of spurs. IuABP knockdown led to an increase in spur curves and distortion of morphology. IuEXT knockdown resulted in reduced spur length and loss of curve and inner epidermal papillae structures. This study provides new insights into the mechanism of spur development in core eudicots.

Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism.

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Pediatric pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) can cause morbidity and mortality in children. Although adult and pediatric PAH share many similarities, many differences have been found in children. Thus, a new classification for pediatric pulmonary hypertensive vascular disease has been proposed. Both child and adult gene mutation carriers with PAH tend to have worse prognoses. Pediatric patients present with better preserved functional class, and parents should pay high attention to any children with unexplained shortness of breath, fatigue or syncope, as symptoms of PAH in children are often misleading. Right heart catheterization is necessary for diagnosis. Although there are few medications approved for pediatric PAH and evidence-based treatment algorithms for children are still lacking, the survival of pediatric patients has been improved significantly since targeted therapies approved for adults were introduced to pediatric patients. PAH in children is unique, and further studies are needed to have a better understanding of it.

Mechanism underlying Fanmugua () leaf multicomponent synergistic therapy for anemia: data mining based on hematopoietic network.

OBJECTIVE: To investigate the underlying mechanism of Fanmugua (Fructus Caricae) Leaf (CPL) multicomponent synergistic therapy for anemia. METHODS: The components were identified in the literature. Six databases were searched for targets of CPL. Enrichment analysis was used to determine the targets associated with anemia and in bone marrow. Based on the Kyoto Encyclopedia of Genes and Genomes database, pathways and targets related to hematopoiesis were obtained. The key targets were obtained by protein-protein interaction analysis. Molecular docking was used to analyze the binding ability of key targets and active components. Bone marrow cells were used as an experimental model to verify the drug efficacy. RESULTS: A total of 139 components and 1868 targets of CPL were retrieved from the literature. By disease enrichment analysis, 543 targets for hemorrhagic anemia, 223 targets for aplastic anemia, and 126 targets for sickle cell anemia were obtained. Target organ enrichment yielded 27, 29, and 20 targets of bone marrow. Based on KEGG pathway enrichment, a total of 47 shared hematopoietic pathways and 42 related targets were found. The key targets were vascular endothelial growth factor A (VEGFA), interleukin 10 (IL-10), platelet-endothelial cell adhesion molecule-1 (PECAM1), C-C motif chemokine 2 (CCL2), and vascular cell adhesion molecule 1 (VCAM1). The CPL active components included ursolic acid, quercetin, and hesperidin. The expression of VEGFA was significantly increased after CPL treatment. Quercetin and ursolic acid acted on VEGFA. Quercetin and Hesperidin acted on VCAM1. Quercetin acted on IL-10, CCL2, VCAM1, and VEGFA. Cell experiments revealed that CPL could promote the proliferation and migration of bone marrow cells. CONCLUSIONS: CPL has the synergistic efficacy of treating anemia through multiple components, targets, and pathways.

Moxibustion ameliorated age-related alterations in neurological behavior and gut microbiota in mice.

OBJECTIVE: To observe the anti-aging effects of moxibustion on age-related alterations in middle-aged mice. METHODS: Thirty, 9-month-old, male ICR mice were randomly divided into the moxibustion and control groups (N = 15). Mice in the moxibustion group were given mild moxibustion at the Guanyuan acupoint for 20 minutes every other day. After 30 treatments, neurobehavior tests, lifespan, gut microbiota composition and splenic gene expression were observed in the mice. RESULTS: Moxibustion improved the locomotor activity as well as motor function, activated the SIRT1-PPARα signaling pathway, ameliorated age-related alterations in gut microbiota, and affected the expression of genes related to energy metabolism in spleen. CONCLUSION: Moxibustion ameliorated age-related alterations in neurobehavior and gut microbiota in middle-aged mice.

[Effects of Chinese herbal medicine Shenxiong Yujing Granule on regeneration of neural cells in rats with diabetes-associated cerebral ischemia].

OBJECTIVE: To establish a rat model of diabetes-associated cerebral ischemia due to qi and yin deficiency and blood stasis, and to investigate the effects of Radix Ginseng, Rhizoma Chuanxiong, Rhizoma Polygonati Odorati and Rhizoma Polygonati Sibirici Granule (Shenxiong Yujing Granule), which has the function of strengthening qi, nourishing yin, and activating blood, on proliferation, differentiation and survival of neural cells in rats with diabetes-associated cerebral ischemia. METHODS: Rats were divided into sham-operation, diabetes plus ischemia reperfusion injury model, Shenxiong Yujing Granule and Radix Ginseng and Rhizoma Chuanxiong Granule (Shenxiong Granule) groups with 20 rats in each. The 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunohistochemical method were used to investigate the proliferation, differentiation and survival of neural cells in dentate gyrus of rats with diabetes-associated cerebral ischemia. RESULTS: The number of newly proliferating cells in subgranular zone of dentate gyrus was increased in the model group, but there was no significant difference compared with 7 day treatment with Shenxiong Yujing Granule. Shenxiong Yujing Granule significantly increased the survival rate and promoted the differentiation of newly proliferating neurons after 21-day treatment (P<0.01). In addition, the beneficial effect of Shenxiong Yujing Granule was considerably greater than that of the Shenxiong Granule (P<0.01). CONCLUSION: Shenxiong Yujing Granule can increase the survival rate and promote the differentiation of newly proliferating neurons in rats with diabetes-associated cerebral ischemia of dual deficiency of qi and yin and blood stasis obstructing the collaterals. The effect is greater than that of Shenxiong Granule.

[Characteristics of runoff and infiltration processes on slope with intergrown biocrusts and herbs]. / ç”Ÿç‰©ç»“çš®ä¸Žè‰æœ¬æ¤ç‰©å ±ç”Ÿå¡é¢çš„äº§æµ-å ¥æ¸—è¿‡ç¨‹ç‰¹å¾.

Biocrusts and herbs coexist in arid and semi-arid areas, playing an important role in soil and water conservation. However, the combined effects of biocrusts and herbs on process and mechanism of runoff and infiltration on slope are still unclear. In this study, simulated rainfall experiments with four treatments, including bare soil, biocrusts, Stipa bungeana and S. bungeana+biocrusts, were designed to investigate runoff, infiltration process and hydrodynamic characteristics of herbs and biocrusts on slope. The results showed that the runoff under the two treatments with biocrusts was stable. The total runoff of four treatments was in the following order: biocrusts > S. bungeana+biocrusts > bare soil > S. bungeana, indicating that biocrusts could inhibit soil infiltration and S. bungeana could promote soil infiltration. At soil depths of 16 cm and 24 cm, the cumulative infiltration of biocrusts treatment was significantly less than that of S. bungeana+biocrusts treatment, suggesting that with the increases of soil depth, S. bungeana reduced the negative effect of biocrusts on soil infiltration. The Froude number was greater than 1 under bare soil and less than 1 under other treatments, which was subcritical flow. Compared with the runoff kinetic energy of the bare soil treatment, the treatments of biocrusts, S. bungeana, and S. bungeana+biocrusts were reduced by 83.3%, 59.5%, and 88.1%, respectively. The variations of hydrodynamic parameters indicated that the role of biocrusts is greater than S. bungeana in regulating runoff.

Bone marrow stromal cell antigen 2(BST2) suppresses the migration and invasion of trophoblasts in preeclampsia by downregulating matrix metallopeptidase 2(MMP2).

Preeclampsia is a grievous pregnancy-related complication with an incidence of approximately 5∼7% in pregnant women. Placental abnormalities and decreased placental perfusion associated with impaired trophoblast invasion are early pathological findings of preeclampsia. BST2 is a multifunctional transmembrane protein that plays critical roles in physiological and pathological processes, but its impacts and mechanisms of action in preeclampsia are inadequately understood. The aim of this manuscript was to investigate the functional impacts of BST2 and MMP2 on the biological behavior of trophoblast cells in preeclampsia. The expression of these proteins and their genes was analyzed by qRT-PCR, western blotting and immunohistochemistry. The results showed that the expression of BST2 and MMP2 was significantly downregulated in preeclampsia. The migration and invasion capacities of HTR-8/SVneo and JAR cells with overexpression or knockdown of BST2 were detected by wound healing assay and Transwell assays. It was found that BST2 overexpression could up-regulate MMP2 expression, and enhance the migration and invasion capacity of HTR-8/SVneo and JAR cells. BST2 knockdown could reverse these effects. MMP2 knockdown could downregulate the invasion capacity of HTR-8/SVneo cells, and MMP2 overexpression reversed these effects. Pearson correlation analysis demonstrated that the expression of MMP2 and BST2 were positively correlated. These results indicate that the downregulation of BST2 lowers MMP2 expression and restraint trophoblast functions, which probably explain its role in the pathogenesis of preeclampsia.

Crab spiders (Araneae, Thomisidae) of Jinggang Mountain National Nature Reserve, Jiangxi Province, China.

A list of 34 thomisid species belonging to 21 genera collected in Jangxi Province of China is provided. Five new species are described: Angaeusxieluae Liu, sp. nov. (♂♀), Lysitelessubspirellus Liu, sp. nov. (♀), Oxytatemucunica Liu, sp. nov. (♀), Phartalingxiufengica Liu, sp. nov. (♀), Stephanopisxiangzhouica Liu, sp. nov. (♀). A new combination is proposed: Ebelingiaforcipata (Song & Zhu, 1993) comb. nov. (ex. Ebrechtella Dahl, 1907). Previously unknown females of E.forcipata (Song & Zhu, 1993), Oxytatebicornis Liu, Liu & Xu, 2017, and Xysticuslesserti Schenkel, 1963 are described for the first time. Stephanopis O Pickard-Cambridge, 1869, a genus previously known from Australasia and South America, is recorded from the Asian mainland for the first time.

A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice.

OBJECTIVE: To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments. METHODS: Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms. RESULTS: The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01). CONCLUSION: The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Overview of human clonorchiasis sinensis in China.

The objective of the survey was to determine the current status, trends and transmission factors for Clonorchis sinensis infection in China and to provide updated information for development control strategies. This was part of a nationwide survey of major human parasitic diseases carried out during 2000-2002 sampled by the stratified randomized cluster sampling method. Fecal examination was conducted using the Kato-Katz thick smear method and egg count per gram of feces (EPG) was determined for the egg-positive patients. A questionnaire and a case-control study were applied to analyze the transmission factors for C. sinensis infection. The overall prevalence rate of C. sinensis infection was 0.58% in 356,629 residents from 688 sampled pilot sites in 31 provinces, autonomous regions and municipalities (PAM) of China. The infection rates of C. sinensis in Guangdong, Jilin, Guangxi Zhuang autonomous region, Anhui and Heilongjiang were higher than the other PAM, they were 5.35, 4.77, 3.71, 0.67 and 0.48%, respectively. In Guangxi, moderate and heavy infections were found in 29.14% and 11.52%, respectively, of the total infected. Heavy infections were not found in any of the other provinces except for 2 heavily infected cases in Heilongjiang. The prevalence rate increased with age for residents aged < 35 years and remained at high levels in those aged 25-60 years. The infection rate in males was 1.64 times that of females. The C. sinensis egg positivity rates in fishermen, businessmen, physicians and teachers were higher than others. Among the 38 ethnic groups, the prevalences in the Han (3.20%) and the Zhuang (3.15%) were the highest; no cases were found among the Zang, Miao, Man and other 29 ethnic groups. Significant differences in prevalences were also found among counties of different economic levels. C. sinensis infection is prevalent in hilly and plains regions of northeast and southcentral China, representing two highly endemic areas in the North and the South. An increasing trend in prevalence was seen in endemic areas. The infection was mainly detected in young and middle aged males. A higher prevalence was observed in those with a better education and a higher income. Consumption of raw (or under-cooked) fresh water fish or shrimp were the main risk factors responsible for transmission of the parasite.