Phylogenetic and ion-response analyses reveal a relationship between gene expansion and functional divergence in the Ca2+/cation antiporter family in Angiosperms.

KEY MESSAGE: Plant CaCA superfamily genes with higher tendency to retain after WGD are more gene expression and function differentiated in ion-response. Plants and animals face different environmental stresses but share conserved Ca2+ signaling pathways, such as Ca2+/Cation transport. The Ca2+/cation antiporters superfamily (CaCAs) is an ancient and widespread family of ion-coupled cation transporters found in all kingdoms of life. We analyzed the molecular evolution progress of the family through comparative genomics and phylogenetics of CaCAs genes from plants and animals, grouping these genes into several families and clades, and identified multiple gene duplication retention events, particularly in the CAX (H+/cation exchanger), CCX (cation/Ca2+ exchanger), and NCL (Na+/Ca2+ exchanger-like) families. The tendency of duplication retention differs between families and gene clades. The gene duplication events were probably the result of whole-genome duplication (WGD) in plants and might have led to functional divergence. Tissue and ion-response expression analyses revealed that CaCAs genes with more highly differentiated expression patterns are more likely to be retained as duplicates than those with more conserved expression profiles. Phenotype of Arabidopsis thaliana mutants showed that loss of genes with a greater tendency to be retained after duplication resulted in more severe growth deficiency. CaCAs genes in salt-tolerant species tended to inherit the expression characteristics of their most recent common ancestral genes, with conservative ion-response expression. This study indicates a possible evolutionary scheme for cation transport and illustrates distinct fates and a mechanism for the evolution of gene duplicates. The increased copy numbers of genes and divergences in expression might have contributed to the divergent functions of CaCAs protein, allowing plants to cope with environmental stresses and adapt to a larger number of ecological niches.

Association between kidney stones and risk of developing stroke: a meta-analysis.

BACKGROUND: Many studies have described the relationship between kidney stones and stroke, but the results are controversial, so we conducted this meta-analysis to estimate the relationship between kidney stones and the risk of developing stroke. METHODS: Studies were marked with a comprehensive search of PubMed, EMBASE, Google, and ISI Web of Science databases through 25 March 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and a random-effects model or fix-effects model was used to compute the pooled combined risk estimate. Heterogeneity was reported as I2. We performed subgroup and sensitivity analysis to assess potential sources of heterogeneity. RESULTS: Eight studies of seven articles involving 3,526,808 participants were included in the meta-analysis. Overall, kidney stones were associated with a moderate risk of stroke incidence (HR, 1.24; 95% CI, 1.11-1.40; I2=79.6%; p=0.000). We conducted a sensitivity analysis by removing the studies that had a high risk of bias. Heterogeneity subsequently decreased significantly, while an increased risk of stroke in patient with kidney stones was again demonstrated (HR, 1.16; 95% CI, 1.11-1.23; I2=28.7%; p=0.000). Stratifying analysis showed that the results were more pronounced for ischemic stroke (HR, 1.14; 95% CI, 1.08-1.22; I2=15.6%; p=0.00) and the follow-up duration ≥10 years (HR, 1.18; 95% CI, 1.10-1.27; I2=31.6%; p=0.003). CONCLUSIONS: Our meta-analysis suggests that patients with kidney stones may have a modestly increased risk of developing stroke, especially in ischemic stroke. More large-scaled and clinical trials should be done to identify the relative impact of kidney stones on stroke outcomes in the future.

Association between NAFLD and risk of prevalent chronic kidney disease: why there is a difference between east and west?

BACKGROUNDS: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. METHODS: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. RESULTS: A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. CONCLUSION: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.

Risk factors for hospital readmission among patients with cirrhosis and ascites in China: a retrospective observational study.

OBJECTIVE: In this investigation, we aimed to explore risk factors for 90-day hospital readmission among patients with cirrhosis and ascites in an Asian population. METHODS: In this retrospective study, we included consecutive patients diagnosed with cirrhosis and ascites hospitalized in Renji Hospital between 2018 and 2022 to elucidate risk factors for 90-day readmission. We conducted multivariate logistic regression analysis to identify readmission risk factors. RESULTS: We included 265 patients with cirrhosis and ascites. A 43% readmission rate was observed within 90 days. After adjustment for multiple covariates, we found that readmission within 90 days was independently linked to reduced levels of hemoglobin (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.97) and serum albumin (OR 0.88, 95% CI 0.83-0.93), and higher Model for End-Stage Liver Disease and sodium (MELD-Na) scores (OR 1.04, 95% CI 1.01-1.07) at discharge. CONCLUSIONS: Patients with cirrhosis who have ascites are frequently rehospitalized within 90 days after discharge. Lower hemoglobin or albumin and higher MELD-Na scores at discharge may be the main risk factors for hospital readmission.

The Short Health Scale: A Valid and Reliable Quality-of-Life Scale for Mainland Chinese Patients with Inflammatory Bowel Disease.

Background: The aim of our study was to translate and validate the mainland Chinese version of the short health scale (SHS), a disease-specific quality-of-life (QoL) scale for patients with inflammatory bowel disease (IBD). Methods: The SHS was translated and validated according to the standard process: a translation and back-translation procedure and a reliability and validation study. Patients with IBD were enrolled, and their QoL was assessed using the SHS, the short inflammatory bowel disease questionnaire (SIBDQ), and the Bristol stool form scale. Reliability (internal consistency reliability, split-half reliability, and test-retest reliability) and validity analyses were performed to evaluate the psychometric characteristics of the SHS. The impacts of different severity of major symptoms on QoL were analyzed by comparing the scores of SHS. Results: A total of 112 patients with IBD (69 with ulcerative colitis and 43 with Crohn's disease) completed the mainland Chinese version of the SHS, and 34 patients completed the SHS a second time within one to two weeks. Cronbach's alpha value of the SHS was 0.90, and its split-half coefficient was 0.83. Intraclass correlation coefficients of the four items ranged from 0.52 to 0.72. All four items of the SHS were significantly associated with the corresponding domains of the SIBDQ, with correlation coefficients ranging from -0.52 to -0.69 (p < 0.001). The results of confirmatory factor analysis indicated a good fit of the one-factor model, with comparative fit index (CFI) = 0.878, normed fit index (NFI) = 0.874, incremental fit index (IFI) = 0.880, and goodness of fit index (GFI) = 0.842. The patients with severe symptoms had higher scores in the SHS than those with no or mild symptoms. Conclusions: The SHS was simple and quick to be used. The SHS had good validity and reliability and was suitable for evaluating the QoL of patients with IBD in mainland China.

[Effects of simulated 5 500 m hypobaric and hypoxia on HPT axis and intestinal flora in rats].

Objective: To investigate the effects of simulated hypoxia environment at an altitude of 5 500 meters on hypothalamic-pituitary-thyroid (HPT) axis and intestinal flora of rats and the correlation between them. Methods: The hypoxia model of adult male SD rats was established by hypobaric chamber with simulated altitude of 5 500 m. The hypoxia groups were set for 1, 3, 7, 14, 21 and 28 days, and the normoxic recovery group were set for 1 and 3 days after hypoxia (8 rats per group, hypoxia time 24h per day). Daily body weight and food intake of rats were recorded. The serum levels of HPT axis hormones were detected by enzyme-linked immunosorbent assay (ELISA). Intestinal flora was analyzed by 16s rDNA sequencing. The correlation between intestinal flora and serum HPT axis hormone was analyzed by Spearman correlation analysis. Results: Compared with the normoxic group, the body weight and food intake were significantly reduced (P＜0.01). In the 1-day and 3-day groups, the levels of thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) were decreased significantly (P＜0.05), the levels of total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4) and free triiodothyronine (FT3) were increased significantly (P＜0.05), and the abundance of Prevotella was decreased significantly (P＜0.05), while those of Parabacteroides, Lactobacillus, Butyricimonas, Bacteroides, Odoribacter and RC4-4 were increased significantly (P＜0.05). In the 14-day, 21-day and 28-day hypoxia groups, the levels of TRH and TSH were decreased significantly (P＜0.05), and the levels of TT4 and TT3 were increased significantly (P＜0.05), and there was no significant difference in other indexes, the abundance of Parabacteroides, Sphaerochaeta, Akkermansia, Elusimicrobium was increased significantly, but that of Lactobacillus and Sutterella was decreased significantly (P＜0.05). Correlation analysis of intestinal flora and HPT axis hormones showed that Butyricimonas, Elusimicrobium and Sutterella were significantly negatively correlated with TRH and TSH (P＜ 0.05), Prevotella, Bacteroides, Odoribacter and Parabacteroides were significantly correlated with TSH, TT4, TT3 and FT4 (P＜ 0.05), respectively. Lactobacillus was significantly correlated with TRH, TSH and FT4 (P＜0.05). Akkermansia was significantly correlated with TRH and FT4 (P＜0.05). RC4-4 was significantly associated with TSH and TT3 (P＜0.05). Conclusion: Hypoxia stress at an altitude simulating 5500 meters significantly changed the composition of the intestinal flora of SD rats. This may be a change in thyroid function adapted to the hypoxia environment, and the degree of change is related to the time of hypoxia stress. The change of intestinal microflora is significantly correlated with the hormone level of HPT axis.

Reliability and validity of the Chinese version of the Test for Respiratory and Asthma Control in Kids (TRACK) in preschool children with asthma: a prospective validation study.

OBJECTIVE: The limited existing asthma control questionnaires that are available for children 5 years of age or younger in China mostly assess only the impairment domain of asthma control. Here, the English version of the Test for Respiratory and Asthma Control in Kids (TRACK) was translated into Chinese and validated for its application in asthma control in preschool children. DESIGN: Prospective validation study. SETTING AND PARTICIPANTS: A total of 321 Chinese preschool children suffering from asthma completed the study from December 2017 to February 2018. METHOD: The TRACK translation into Chinese employed the translation and back translation technique. The caregivers of the preschool children with asthma symptoms completed TRACK during two clinical visits over 4-6 weeks. Moreover, the physicians completed a Global Initiative for Asthma (GINA)-based asthma control survey at both visits. The utility of TRACK for assessing the change in asthma control status and its reliability and discriminant validity were evaluated. RESULTS: The Chinese version of TRACK showed internal consistency reliability values of 0.63 and 0.71 at each visit, respectively (Cronbach's α). The test-retest reliability was 0.62 for individuals whose GINA-based assessment results were the same at both visits (n=206). The TRACK scores for the children in the various asthma control categories were significantly different (p<0.001). Children recommended for increased treatment by the physicians had lower TRACK scores than those recommended for no change in treatment or decreased treatment (p<0.001). CONCLUSION: The study verifies the validity and reliability of the Chinese version of TRACK. Changes in the TRACK scores effectively reflected the level of asthma control in preschool children and guided further treatment strategies. TRIAL REGISTRATION NUMBER: NCT02649803.

Apoptosis induced by (di-isopropyloxyphoryl-Trp)2-Lys-OCH3 in K562 and HeLa cells.

According to the method used in our laboratory,our group synthesized (DIPP-Trp)2-Lys-OCH 3. It inhibited the proliferation of K562 and HeLa cells in a dose-and time-dependent manner with an IC 50 of 15.12 and 42.23 microM, respectively. (DIPP-Trp) 2-Lys-OCH3 induced a dose-dependent increase of the G2/M cell population in K562 cells, and S cell population in HeLa cells;the sub-G0 population increased dramatically in both cell lines as seen by PI staining experiments using a FACS Calibur Flow cytometer (BeckmanCoulter,USA). Phosphatidylserine could signi?cantly translocate to the surface of the membrane in (DIPP-Trp)2-Lys-OCH3-treated K562 and HeLa cells. The increase of an early apoptotic population was observed in a dose-dependent manner by both annexin-FITC and PI staining. It was concluded that (DIPP-Trp) 2-Lys-OCH3 not only induced cells to enter into apoptosis,but also affected the progress of the cell cycle. It may have arrested the K562 and HeLa cells in the G 2/M,S phases,respectively. The apoptotic pathway was pulsed at this point,resulting in the treated cells entering into programmed cell death.(DIPP- Trp)-Lys-OCH is a potential anticancer drug that intervenes in the signalling pathway.

Effect of glycated hemoglobin index and mean arterial pressure on acute ischemic stroke prognosis after intravenous thrombolysis with recombinant tissue plasminogen activator.

To determine whether glycated hemoglobin and mean arterial pressure (MAP) during thrombolysis are prognostic factors of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS).A total of 125 AIS patients, who received rt-PA intravenous thrombolysis in our hospital, were included into the present study, and divided into good prognosis group and poor prognosis group. Univariate and multivariate logistic regression analyses were used to determine the prognostic factors of AIS treated by rt-PA thrombolysis, Spearman correlation analysis was used to analyze the correlation of the accumulated cigarette consumption in the smoking subgroup and glycated hemoglobin in the diabetic subgroup with the prognosis after intravenous thrombolysis and the symptomatic intracranial hemorrhage (sICH).Univariate analysis revealed that the interval from onset to thrombolysis, baseline National Institutes of Health Stroke Scale (NIHSS) score, MAP during thrombolysis and DRAGON score were prognostic factors. Multivariate logistic regression analysis revealed that baseline NIHSS score and MAP during thrombolysis were independent prognostic factors for rt-PA thrombolysis. Furthermore, the glycated hemoglobin index was positively correlated with the incidence of sICH.The NIHSS score before thrombolysis and MAP during thrombolysis were independent factors for the prognosis of AIS treated by thrombolysis. The higher the glycated hemoglobin index of diabetic patients, the more likely they are to develop sICH, the glycated hemoglobin index was negatively correlated with the prognosis after intravenous thrombolysis. The accumulated cigarette consumption was negatively correlated with the prognosis after intravenous thrombolysis.

[Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives bearing dithiocarbamate chains].

A series of 4(3H)-quinazolinone derivatives bearing dithiocarbamate side chains have been synthesized through the reaction of 6-bromomethyl-2-methyl-4(3H)-quinazolinone with CS2 and various amines in the presence of anhydrous K3PO4, and their structures were confirmed with ESI-MS, H NMR, elemental analysis or HRMS. The target compounds 8a -8q were tested for their in vitro antitumor activity against human myelogenous leukaemia K562 and human Hela cell lines by means of colorimetric MTT assay. Among the tested compounds, 8q exhibited in vitro inhibitory activity against K562 and Hela cells with IC50 values of 0.5 and 12.0 micromol x L(-01), respectively. Therefore, compound 8q is worthy to be a lead compound for the design and synthesis of new antitumor agents.

Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression.

Clinical applications of siRNA are being hindered by poor intracellular uptake and enzymatic degradation. To address these problems, we devised an oral delivery system for telomerase reverse transcriptase siRNA using N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles (HNP). Both the porous structure and the positive charge of HNP facilitated siRNA encapsulation. The outer coating of HTCC not only protected siRNA from enzymatic degradation, but also improved siRNA permeability in intestine tract. In vivo and in vitro experiments proved that HNP could effectively deliver siRNA to lesion site and further into tumor cells. On the basis of confirming the antitumor activity of HNP:siRNA, we continued to encapsulate a hydrophobic chemotherapeutic drug-paclitaxel (PTX) into HNP to form a "two-in-one" nano-complex (HNP:siRNA/PTX). We demonstrated that HNP:siRNA/PTX could simultaneously ferry siRNA and PTX into tumor cells and increase drug concentration, which, in particular, was much more effective in tumor suppression than that of traditional cocktail therapy. These results suggested that the HNP, as a powerful delivery system for both siRNA and chemotherapeutic drug, would have a far-reaching application in human cancer therapy.

Nanoparticles-based multi-adjuvant whole cell tumor vaccine for cancer immunotherapy.

Whole cell tumor vaccine (WCTV), as a potential treatment modality, elicits limited immune responses because of the poor immunogenicity. To address this issue, researchers have attempted to transduce a cytokine adjuvant into tumor cells, but these single-adjuvant WCTVs curtail the high expectations. In present study, we constructed a multi-adjuvant WCTV based on the nanoparticles modified with cell penetrating peptide, which could facilitate the transportation of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2) into tumor cells. After inactivation, as-designed multi-adjuvant WCTV exhibited programmed promotions on DC recruitment, antigen presentation, and T-cell activation. In vivo evaluations demonstrated the satisfactory effects on tumor growth suppression, metastasis inhibition, and recurrence prevention. Therefore, the nanoparticles-based multi-adjuvant WCTV may serve as a high-performance treatment for anti-tumor immunotherapy.

[Inducement effect of (DIPP-L-Trp)2-L-Lys-OCH3 on apoptosis of K562 cells through mitochondrial-dependent pathway].

BACKGROUND & OBJECTIVE: Phosphorylation of protein and peptide plays an important role in life activity. Some phosphoryl peptides are found to have activities to inhibit proliferation of tumor cells, but the involved mechanisms are unclear. This study was designed to investigate cell apoptosis induced by (O,O-diisopropyl phosphoryl-L-tryptophan)(2)-L-lysine methyl ester [(DIPP-L-Trp)(2)-L-Lys-OCH(3)], and its mechanism in K562 cells. METHODS: K562 cells were double stained by AnnexinV-FITC and propidium iodide (PI) to detect (DIPP-L-Trp)(2)-L-Lys-OCH(3)-induced apoptosis by flow cytometry (FCM). After treatment of different concentrations of (DIPP-L-Trp)(2)-L-Lys-OCH(3), K562 cells were stained by rhodamine123 and PI to detect changes in membrane potential (Delta Psi m), or stained by 2',7'-dichlorofluorescein diacetate (DCFH-DA) to detect reactive oxygen species (ROS) of mitochondrial by FCM. RESULTS: When treated with 50 microg/ml of (DIPP-L-Trp)(2)-L-Lys-OCH(3) for 24 h, apoptosis rate of K562 cells was 61.9%, Delta Psi m was decreased in 93.6% of K562 cells,and ROS production was decreased. Both Delta Psi m and ROS production in K562 cells mitochondria were decreased with the increasing concentration and extending treatment time of (DIPP-L-Trp)(2)-L-Lys-OCH(3). CONCLUSION: (DIPP-L-Trp) (2)-L-Lys-OCH(2) could induce apoptosis in K562 cells, which might relate with down-regulation of mitochondrial Delta Psi m and reduction of ROS production.

[Effects of budesonide on chronic airway inflammation in guinea pigs sensitized with repeated exposure to allergen].

OBJECTIVE: Inhaled glucocorticosteroids (ICS) remains the first line controller medication for chronic airway inflammation in asthma till now. If the impact of allergen could not be eliminated, how would the improvement of airway inflammation be achieved with inhaled glucocorticosteroids therapy? What was its effect on airway remodeling? In this study, an animal model of asthma was established and the effects of budesonide on airway allergic inflammation and extracellular matrix (ECM) deposition in sensitized guinea pigs with repeated exposure to allergen were investigated. METHODS: Thirty-two male Hartley guinea pigs were randomly divided into four groups with 8 in each group: (A) Group of repeated exposure to ovalbumin (OVA), (B) Group of repeated exposure to OVA plus budesonide (BUD) intervention, (C) Group of stopping repeated exposure to OVA plus stopping BUD intervention, (D) Control group. At 24 h after the last OVA challenge (8 weeks after the first OVA challenge), bronchoalveolar lavage fluid (BALF) was collected from each animal. Total and differential leukocyte counts in BALF was performed on cell suspension smear stained with May-Grünwald-Giemsa (MGG) method. The upper lobe of right lung was removed and regularly fixed, then paraffin embedded lung tissues sections were prepared. The count of eosinophils infiltrated in the airway wall was performed on H&E stained lung tissue sections with LEICA Q500IW computerized image analysis system. Fibronectin and collagen type III (Col-III) deposited in the airway wall were detected by immunohistochemical staining on the paraffin embedded lung tissues sections. The intensity of positive reaction of fibronectin or Col-III deposited in the airway wall was analyzed with LEICA Q500IW computerized image analysis system. RESULTS: The count of eosinophils in BALF (x 10(5)/ml) of group A and B were higher than that of group C and D (35.70 +/- 25.22, 11.49 +/- 5.51 vs. 1.00 +/- 0.90, 1.02 +/- 0.78, P < 0.01), the difference between group A and B, group B and C was significant. The count of eosinophils infiltrated at each level of airway wall in group A and B were higher than that of group C and D (large airway: 6.95 +/- 2.28, 1.54 +/- 1.09 vs. 0.76 +/- 0.45, 0.88 +/- 0.25; medial airway: 9.22 +/- 3.89, 3.99 +/- 2.3 vs. 1.25 +/- 1.20, 0.64 +/- 0.36; small airway: 11.56 +/- 4.02, 2.67 +/- 1.15 vs. 1.32 +/- 0.83, 0.43 +/- 0.24, P < 0.01), the difference between group A and B, group B and C was significant. The gray values of fibronectin deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 122 +/- 22, 174 +/- 23 vs. 219 +/- 34, 229 +/- 20; small airway 135 +/- 29, 165 +/- 41 vs. 236 +/- 20, 220 +/- 16, P < 0.05), the difference between group A and B, group B and C was significant. The gray values of Col-III deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 153 +/- 21, 174 +/- 22 vs. 189 +/- 14, 200 +/- 18; small airway 133 +/- 23, 176 +/- 20 vs. 191 +/- 14, 198 +/- 20, P < 0.05), the difference between group A and B was significant. CONCLUSION: Inhaled budesonide could partially inhibit allergic inflammation and ECM deposition in airway wall in guinea pig chronic asthma model with repeated exposure to allergen. Early inhaled budesonide combined with avoidance of OVA exposure could completely inhibit allergic inflammation and ECM deposition. These results suggest that the inhibitory effect on airway allergic inflammation and airway remodeling of inhaled glucocorticosteroids would be limited when the allergen factor could not be avoided.

Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains.

A series of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains were synthesized and tested for their in vitro antitumor activity against human myelogenous leukemia K562 cells. Among them, (3,4-dihydro-2-methyl-4-oxoquinazolin-6-yl)methyl 4-(4-fluorophenyl)piperazine-1-carbodithioate 8q exhibited significant inhibitory activity against K562 cells with IC(50) value of 0.5 microM.

[Relationship between bronchial hyperresponsiveness and the peripheral obstruction in stable asthmatic children].

OBJECTIVE: Asthma is the most common chronic respiratory disease of children. The association between asthma and bronchial hyperresponsiveness (BHR) has been well-demonstrated. The objective of the study was to investigate relationship between the bronchial responsiveness and the peripheral obstruction in stable asthmatic children. METHODS: Thirty-nine children with stable asthma, 28 boys and 11 girls with a mean age of 128 (77 - 197) months, received the bronchial provocation test by the maximal expiratory flow-volume (MEFV) curve measurement. The children were divided into two groups: one with maximal mid-expiratory flow (MMEF) < 80% (n = 15) and the other with MMEF >/= 80% (n = 24). Positive rates of bronchial provocation test were compared between groups of MMEF < 80% and >/= 80% and between the children whose relief duration was 12 months (n = 13). Statistical analysis was performed by using Chi-square, rank sum test or t test (SPSS10.0), P values < 0.05 were considered significant. RESULTS: In the 39 stable asthmatic children, 15 (38%) were detected MMEF < 80% and 28 (72%) had BHR. There was no significant difference in BHR between the children with MMEF < 80% and those with MMEF >/= 80% (P > 0.05). There was no significant difference in BHR between the children whose relief duration was 12 months (P > 0.05), either. CONCLUSIONS: The stable asthmatic children still had peripheral obstruction and BHR, which indicated the presence of airway inflammation. There was no significant difference in BHR between the children whose relief duration was 12 months.

Embryonic hatching enzyme strypsin/ISP1 is expressed with ISP2 in endometrial glands during implantation.

Embryo hatching and outgrowth are the first critical steps on the way to a successful pregnancy. It is generally held that serine proteases are responsible for this process, although the exact mechanisms of action are not clearly understood. Recently, we described two novel implantation serine proteinase (ISP) genes that are expressed during the implantation period. The ISP1 gene encodes the embryo-derived enzyme strypsin, which is necessary for blastocyst hatching in vitro and the initiation of invasion. The ISP2 gene, which encodes a related tryptase, is expressed in endometrial glands and is regulated by progesterone during the peri-implantation period. Based on similarities between ISP2 gene expression and that of a progesterone-regulated lumenal serine proteinase activity associated with lysis of the zona pellucida, we have suggested that the strypsin related protein, ISP2, may encode a zona lysin proteinase. As tryptases naturally assemble to form tetrameric structures, we have hypothesized that ISP1 and ISP2 tetramerize to form strypsin and lysin, respectively. In this study, we demonstrate that like ISP2, the ISP1 gene is also expressed in endometrial glands and is positively regulated by progesterone during implantation. Using in situ hybridization of adjacent tissue sections, we show that the ISP1 and ISP2 genes are co-expressed within the endometrial gland. Following evidence that ISP1 and 2 can efficiently form homotetramers and heterotetramers in silico, we suggest that ISP heterotetramers may be also be secreted into the uterine lumen during the implantation period. That the embryonic hatching enzyme, may also be secreted into the uterine lumen from uterus, may provide insight into the mechanisms of hatching and implantation initiation.